Modeling of TDP-43 proteinopathy by chronic oxidative stress identifies rapamycin as beneficial in ALS patient-derived 2D and 3D iPSC models.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized neuropathologically by TDP-43 proteinopathy with loss of TDP-43 nuclear splicing activity and formation of cytoplasmic TDP-43 aggregates. The lack of suitable experimental models of TDP-43 proteinopathy has hampered the discovery of effective therapies. We already showed that chronic and mild oxidative insult by sodium arsenite (ARS) triggered TDP-43 cytoplasmic aggregation and stress granules (SGs) formation in ALS patient-derived fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs).

NEK1 haploinsufficiency worsens DNA damage, but not defective ciliogenesis, in C9ORF72 patient-derived iPSC-motoneurons.

The hexanucleotide G4C2 repeat expansion (HRE) in C9ORF72 gene is the major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to both loss- and gain-of-function pathomechanisms. The wide clinical heterogeneity among C9ORF72 patients suggests potential modifying genetic and epigenetic factors. Notably, C9ORF72 HRE often co-occurs with other rare variants in ALS/FTD-associated genes, such as NEK1, which encodes for a kinase involved in multiple cell pathways, including DNA damage response and ciliogenesis.

The duration discrimination respiratory task: A new test to measure respiratory interoceptive accuracy.

Interoception, which refers to the perception of body's internal state, is implicated in emotional processes and psychopathological disorders. Over the last decades, different tools have been developed to measure interoceptive accuracy, or the ability to accurately perceive physiological signals. Most of these tools have focused on cardiac interoception, but respiratory interoception has been less investigated due to the more complex and less portable equipment required.

Human motor neurons derived from induced pluripotent stem cells are susceptible to SARS-CoV-2 infection.

Introduction: COVID-19 typically causes Q7 respiratory disorders, but a high proportion of patients also reports neurological and neuromuscular symptoms during and after SARSCoV-2 infection. Despite a number of studies documenting SARS-CoV-2 infection of various neuronal cell populations, the impact of SARS-CoV-2 exposure on motor neuronal cells specifically has not been investigated so far.

Methods: Thus, by using human iPSC-derived motor neurons (iPSC-MNs) we assessed: (i) the expression of SARS-CoV-2 main receptors; (ii) iPSC-MN infectability by SARS-CoV-2; and (iii) the effect of SARS-CoV-2 exposure on iPSC-MN transcriptome.

Analysis of normal repeat length as possible disease modifier in amyotrophic lateral sclerosis.

The hexanucleotide repeat (HR) expansion is the main genetic cause of amyotrophic lateral sclerosis (ALS), with expansion size from 30 to >4000 units. Normal HR length is polymorphic (2-23 repeats) with alleles >8 units showing a low frequency in the general population. This study aimed to investigate if the normal HR length influences gene expression and acts as disease modifier in ALS patients negative for mutation (ALS-C9Neg).

Exploring epigenetic drift and rare epivariations in amyotrophic lateral sclerosis by epigenome-wide association study.

During the last decades, our knowledge about the genetic architecture of sporadic amyotrophic lateral sclerosis (sALS) has significantly increased. However, besides the recognized genetic risk factors, also the environment is supposed to have a role in disease pathogenesis. Epigenetic modifications reflect the results of the interaction between environmental factors and genes and may play a role in the development and progression of ALS.

The role of semantic assessment in the differential diagnosis between late-life depression and Alzheimer's disease or amnestic mild cognitive impairment: systematic review and meta-analysis.

Object: The cognitive complaints encountered in late-life depression (LLD) make it difficult to distinguish from amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) based on an analysis of neurocognitive disorders. The hypothesis of the early impairment of semantic memory in AD and aMCI is considered a potential differential cognitive clue, but the absence of this impairment has not yet been confirmed in  LLD.

Method: Based on the PRISMA method, we systematically seek neuropsychological assessments of individuals with LLD, the present study included 31 studies representing 3291 controls and 2820 people with LLD.

Integrated 3D Mapping and Diagnosis for the Structural Assessment of Architectural Heritage: Morano's Parabolic Arch.

The architectural heritage of the 20th century is affected by several conservation problems in terms of material preservation, structural analysis, and reuse. Among these, material degradation and durability issues are the ones that have the most effect on the health state and, consequently, the survival of the constructions of the period. In order to conduct a proper analysis for preservation purposes, an interdisciplinary approach is necessary.

Physiological reactivity at rest and in response to social or emotional stimuli after a traumatic brain injury: A systematic review.

Unlabelled: Numerous studies have shown that alterations in physiological reactivity (PR) after traumatic brain injury (TBI) are possibly associated with emotional deficits. We conducted a systematic review of these studies that evaluated PR in adults with moderate-to-severe TBI, either at rest or in response to emotional, stressful, or social stimuli. We focused on the most common measures of physiological response, including heart rate (HR), heart rate variability (HRV), respiratory sinus arrhythmia (RSA), electrodermal activity (EDA), salivary cortisol, facial electromyography (EMG), and blink reflex.

Generation of an iPSC line from a patient with spastic paraplegia type 10 carrying a novel mutation in KIF5A gene.

We generated an iPSC line from a patient with spastic paraplegia type 10 (SPG10) carrying the novel missense variant c.50G > A (p.R17Q) in the N-terminal motor domain of the kinesin family member 5A (KIF5A) gene.

Late-Life Depression, Cognitive Impairment, and Relationship with Alzheimer's Disease.

This narrative review aimed to explore the existing knowledge in order to examine the multiple forms of late-life depression (LLD) within a non-neurodegenerative or a neurodegenerative context, in particular Alzheimer's disease (AD). This review will first provide information about different pathogenic hypotheses proposed to describe LLD when it is not linked to a neurodegenerative context. Within the presentation of these syndromes, the literature reports thymic and cognitive specific features and highlights a common preponderance of cognitive impairment, and particularly executive.

Milling and comilling Praziquantel at cryogenic and room temperatures: Assessment of the process-induced effects on drug properties.

This study is a comprehensive evaluation of praziquantel (PZQ) behavior upon grinding considering the influence of milling temperature (cryogenic vs room temperature), frequency and time and presence of polymers (milled raw PZQ vs comilled PZQ/povidone and PZQ/crospovidone at 50:50 w/w) on two experimental responses (residual crystallinity and PZQ recovery). To this aim a full factorial design was set up and the responses of the experimental design were statistically assessed. The powder temperature, measured in different milling conditions, was found to increase with increasing milling frequency and time, up to a maximum recorded value of 46.

Immunomodulation mediated by a herbal syrup containing a standardized Echinacea root extract: a pilot study in healthy human subjects on cytokine gene expression.

In this study, the immunomodulatory effect of a triply standardized Echinacea angustifolia root extract (Polinacea(®)) was evaluated in 10 healthy subjects. Ten ml of syrup containing one hundred mg of extract (corresponding to 4.7 mg of Echinacoside and 8.

The Sacred Mountain of Varallo in Italy: seismic risk assessment by acoustic emission and structural numerical models.

We examine an application of Acoustic Emission (AE) technique for a probabilistic analysis in time and space of earthquakes, in order to preserve the valuable Italian Renaissance Architectural Complex named "The Sacred Mountain of Varallo." Among the forty-five chapels of the Renaissance Complex, the structure of the Chapel XVII is of particular concern due to its uncertain structural condition and due to the level of stress caused by the regional seismicity. Therefore, lifetime assessment, taking into account the evolution of damage phenomena, is necessary to preserve the reliability and safety of this masterpiece of cultural heritage.

Drug salt formation via mechanochemistry: the case study of vincamine.

In the present research a salt of vincamine, a poorly bioavailable indole alkaloid derived from the leaves of Vinca minor L., was synthesized in the solid state by means of a mechanochemical process employing citric acid as a reagent. The mechanochemical process was adopted as a solvent-free alternative to classical citrate synthetic route that involves the use of solvents.

Mechanochemically induced disordered structures of vincamine: the different mediation of two cross-linked polymers.

The aims of this research were to prepare highly bioavailable binary cogrounds (vincamine-AcDiSol(®) or PVP-Cl) by means of a mechanochemical process and to study the mediation of each polymer in the induction of physical transformations of the drug. From a set of fifteen cogrounds for each crosslinked polymer, two samples were selected in each group on the basis of the AUC of in vitro dissolution profiles with the help of a statistical comparison. The chosen samples were analysed by means of TEM, XRPD, Raman-spectroscopy/imaging, SSNMR, also including the study of (1)H spin-lattice relaxation times.

Enhanced oral bioavailability of vinpocetine through mechanochemical salt formation: physico-chemical characterization and in vivo studies.

Purpose: Enhancing oral bioavailability of vinpocetine by forming its amorphous citrate salt through a solvent-free mechanochemical process, in presence of micronised crospovidone and citric acid.

Methods: The impact of formulation and process variables (amount of polymer and citric acid, and milling time) on vinpocetine solubilization kinetics from the coground was studied through an experimental design. The best performing samples were characterized by employing a multidisciplinary approach, involving Differential scanning calorimetry, X-ray diffraction, Raman imaging/spectroscopy, X-ray photoelectron spectroscopy, solid-state NMR spectroscopy, porosimetry and in vivo studies on rats to ascertain the salt formation, their solid-state characteristics and oral bioavailability in comparison to vinpocetine citrate salt (Oxopocetine(®)).

Multidisciplinary approach on characterizing a mechanochemically activated composite of vinpocetine and crospovidone.

Significant improvement of solubilization kinetics of poorly soluble vinpocetine was obtained through a mechanochemical activation process in presence of micronized crospovidone. Drug-to-polymer weight ratio and milling time variables resulted to have statistically significant impacts on the activation of the product. The complete amorphization was obtained in the coground with the highest crospovidone contents (>80% wt), milled for the longest time (180 min).

Pharmacokinetics and immunomodulatory effects of phytotherapeutic lozenges (bonbons) with Echinacea purpurea extract.

The relative bioavailability of the major alkamides, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, from Echinacea purpurea phytotherapeutic lozenges at three different dose levels (0.07, 0.21 and 0.

Conservative treatment of high grade superficial bladder tumours.

Aim Of The Study: To review our previous experience in the treatment of high grade superficial bladder tumour.

Material And Methods: Data from 71 consecutive patients (12 women and 59 men) with high grade (G3) superficial (Ta-T1) bladder tumour were considered. After endoscopic treatment 31 patients received intravesical immunotherapy with Bacillus Calmette Guerin (BCG), 14 patients were treated with a combined scheme of intravesical chemotherapy and immunotherapy and respectively 3 patients and one patient with intravesical chemotherapy with mitomycin (MMC) or epirubicin (EPI) alone.

[Bladder hernia: a clinical case].

The Authors report a case of inguinal bladder hernia and briefly refer about the different kinds of this rare pathology which is often associated to the commonest inguinal hernia. They, moreover, point out the surgical treatment which has to aim to the repositioning of the bladder and to solve the cervicovesical obstruction.

[A new biological irradiator for the laboratory].

The use of high doses (15-20 Gy) of X- or gamma-rays to irradiate blood-derived materials is a common practice by now. It is usual especially when materials must be transfused into non-immunocompetent patients. This is done to avoid the so-called GVH disease.

Quantitative analysis of the Hopf bifurcation in the Goodwin n-dimensional metabolic control system.

We study, from a quantitative point of view, the Hopf bifurcation in an ODE model of feedback control type introduced by Goodwin (1963) to describe the dynamics of end-product inhibition of gene activity. We formally prove that the exchange of linear stability of the positive equilibrium in the n-dimensional Goodwin system with equal reaction constants coexists with a Hopf bifurcation of nontrivial periodic solutions emanating from this equilibrium, without any further restriction on the dimension n greater than or equal to 3 or on the Hill coefficient. The direction of the bifurcation and the stability and the period of the bifurcating orbits are estimated by means of the algorithm proposed by Hassard et al.