Self-reported gait unsteadiness in mildly impaired neurological patients: an objective assessment through statistical gait analysis

Background Self-reported gait unsteadiness is often a problem in neurological patients without any clinical evidence of ataxia, because it leads to reduced activity and limitations in function. However, in the literature there are only a few papers that address this disorder. The aim of this study is to identify objectively subclinical abnormal gait strategies in these patients. Methods Eleven patients affected by self-reported unsteadiness during gait (4 TBI and 7 MS) and ten healthy subjects underwent gait analysis while walking back and forth on a 15-m long corridor. Time-distance parameters, ankle sagittal motion, and muscular activity during gait were acquired by a wearable gait analysis system (Step32, DemItalia, Italy) on a high number of successive strides in the same walk and statistically processed. Both self-selected gait speed and high speed were tested under relatively unconstrained conditions. Non-parametric statistical analysis (Mann-Whitney, Wilcoxon tests) was carried out on the means of the data of the two examined groups. Results The main findings, with data adjusted for velocity of progression, show that increased double support and reduced velocity of progression are the main parameters to discriminate patients with self-reported unsteadiness from healthy controls. Muscular intervals of activation showed a significant increase in the activity duration of the Rectus Femoris and Tibialis Anterior in patients with respect to the control group at high speed. Conclusions Patients with a subjective sensation of instability, not clinically documented, walk with altered strategies, especially at high gait speed. This is thought to depend on the mechanisms of postural control and coordination. The gait anomalies detected might explain the symptoms reported by the patients and allow for a more focused treatment design. The wearable gait analysis system used for long distance statistical walking assessment was able to detect subtle differences in functional performance monitoring, otherwise not detectable by common clinical examination

Entanglement sharing in E⊗ϵE\otimes\epsilon Jahn-Teller model in the presence of a magnetic field

We discuss the ground state entanglement of the $E\otimes\epsilon$ Jahn-Teller model in the presence of a strong transverse magnetic field as a function of the vibronic coupling strength. A complete characterization is given of the phenomenon of entanglement sharing in a system composed by a qubit coupled to two bosonic modes. Using the residual $I$-tangle, we find that three-partite entanglement is significantly present in the system in the parameter region near the bifurcation point of the corresponding classical model

Entanglement of a qubit coupled to a resonator in the adiabatic regime

We discuss the ground state entanglement of a bi-partite system, composed by a qubit strongly interacting with an oscillator mode, as a function of the coupling strenght, the transition frequency and the level asymmetry of the qubit. This is done in the adiabatic regime in which the time evolution of the qubit is much faster than the oscillator one. Within the adiabatic approximation, we obtain a complete characterization of the ground state properties of the system and of its entanglement content.Comment: 6 pages, 7 figure

Traumatic brain injury and NADPH oxidase: A deep relationship

Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI

Traumatic brain injury and NADPH oxidase: A deep relationship

Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI

Cancer treatment-induced oral mucositis

Oral mucositis is one of the main complications in non-surgical cancer treatments. It represents the major dose-limiting toxicity for some chemotherapeutic agents, for radiotherapy of the head and neck region and for some radiochemotherapy combined treatments. Many reviews and clinical studies have been published in order to define the best clinical protocol for prophylaxis or treatment of mucositis, but a consensus has not yet been obtained. This paper represents an updated review of prophylaxis and treatment of antineoplastic-therapy-related mucositis using a MEDLINE search up to May 2006, in which more than 260 clinical studies have been found. They have been divided according to antineoplastic therapy (chemotherapy, radiotherapy, chemo-radiotherapy, high-dose chemotherapy). The prophylactic or therapeutic use of the analysed agents, the number of enrolled patients and the study design (randomized or not) were also specified for most studies. Accurate pre-treatment assessment of oral cavity hygiene, frequent review of symptoms during treatment, use of traditional mouthwashes to obtain mechanical cleaning of the oral cavity and administration of some agents like benzydamine, imidazole antibiotics, tryazolic antimycotics, povidone iodine, keratinocyte growth factor and vitamin E seem to reduce the intensity of mucositis. Physical approaches like cryotherapy, low energy Helium-Neon laser or the use of modern radiotherapy techniques with the exclusion of the oral cavity from radiation fields have been shown to be efficacious in preventing mucositis onset. Nevertheless a consensus protocol of prophylaxis and treatment of oral mucositis has not yet been obtained

An Integrated In Silico and In Vitro Approach for the Identification of Natural Products Active against SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has provoked a global health crisis due to the absence of a specific therapeutic agent. 3CLpro (also known as the main protease or Mpro) and PLpro are chymotrypsin-like proteases encoded by the SARS-CoV-2 genome, and play essential roles during the virus lifecycle. Therefore, they are recognized as a prospective therapeutic target in drug discovery against SARS-CoV-2 infection. Thus, this work aims to collectively present potential natural 3CLpro and PLpro inhibitors by in silico simulations and in vitro entry pseudotype-entry models. We screened luteolin-7-O-glucuronide (L7OG), cynarin (CY), folic acid (FA), and rosmarinic acid (RA) molecules against PLpro and 3CLpro through a luminogenic substrate assay. We only reported moderate inhibitory activity on the recombinant 3CLpro and PLpro by L7OG and FA. Afterward, the entry inhibitory activity of L7OG and FA was tested in cell lines transduced with the two different SARS-CoV-2 pseudotypes harboring alpha (α) and omicron (o) spike (S) protein. The results showed that both compounds have a consistent inhibitory activity on the entry for both variants. However, L7OG showed a greater degree of entry inhibition against α-SARS-CoV-2. Molecular modeling studies were used to determine the inhibitory mechanism of the candidate molecules by focusing on their interactions with residues recognized by the protease active site and receptor-binding domain (RBD) of spike SARS-CoV-2. This work allowed us to identify the binding sites of FA and L7OG within the RBD domain in the alpha and omicron variants, demonstrating how FA is active in both variants. We have confidence that future in vivo studies testing the safety and effectiveness of these natural compounds are warranted, given that they are effective against a variant of concerns

The Versatile Molecular Complex Component LC8 Promotes Several Distinct Steps of Flagellar Assembly

LC8 is present in various molecular complexes. However, its role in these complexes remains unclear. We discovered that although LC8 is a subunit of the radial spoke (RS) complex in Chlamydomonas flagella, it was undetectable in the RS precursor that is converted into the mature RS at the tip of elongating axonemes. Interestingly, LC8 dimers bound in tandem to the N-terminal region of a spoke phosphoprotein, RS protein 3 (RSP3), that docks RSs to axonemes. LC8 enhanced the binding of RSP3 N-terminal fragments to purified axonemes. Likewise, the N-terminal fragments extracted from axonemes contained LC8 and putative spoke-docking proteins. Lastly, perturbations of RSP3’s LC8-binding sites resulted in asynchronous flagella with hypophosphorylated RSP3 and defective associations between LC8, RSs, and axonemes. We propose that at the tip of flagella, an array of LC8 dimers binds to RSP3 in RS precursors, triggering phosphorylation, stalk base formation, and axoneme targeting. These multiple effects shed new light on fundamental questions about LC8-containing complexes and axoneme assembly

Synthesis and biological evaluation of phosphonated dihydroisoxazole nucleosides

Phosphonated isoxazolinyl nucleosides have been prepared via 1,3-dipolar cycloaddition reaction of nitrile oxides with corresponding vinyl or allyl nucleobases for antiviral studies. The cytotoxicity, the anti-HSV activity and the RT-inhibitory activity of the obtained compounds were evaluated and compared with those of AZT and diethyl{(10SR,40RS)-10-[[(5-methyl-2,4-dioxo-3,4- dihydropyrimidin-1(2H)-yl)]-30-methyl-20-oxa-30-azacyclopent-40-yl]}methylphosphonate, a saturated phosphonated dihydroisoxazole nucleoside analogue