Chitinase Signature in the Plasticity of Neurodegenerative Diseases.

Several reports have pointed out that Chitinases are expressed and secreted by various cell types of central nervous system (CNS), including activated microglia and astrocytes. These cells play a key role in neuroinflammation and in the pathogenesis of many neurodegenerative disorders. Increased levels of Chitinases, in particular Chitotriosidase (CHIT-1) and chitinase-3-like protein 1 (CHI3L1), have been found increased in several neurodegenerative disorders. Although having important biological roles in inflammation, to date, the molecular mechanisms of Chitinase involvement in the pathogenesis of neurodegenerative disorders is not well-elucidated. Several studies showed that some Chitinases could be assumed as markers for diagnosis, prognosis, activity, and severity of a disease and therefore can be helpful in the choice of treatment. However, some studies showed controversial results. This review will discuss the potential of Chitinases in the pathogenesis of some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, to understand their role as distinctive biomarkers of neuronal cell activity during neuroinflammatory processes. Knowledge of the role of Chitinases in neuronal cell activation could allow for the development of new methodologies for downregulating neuroinflammation and consequently for diminishing negative neurological disease outcomes.

Identifying the Effects of Age and Speed on Whole-Body Gait Symmetry by Using a Single Wearable Sensor.

Studies on gait symmetry in healthy population have mainly been focused on small range of age categories, neglecting Teenagers (13-18 years old) and Middle-Aged persons (51-60 years old). Moreover, age-related effects on gait symmetry were found only when the symmetry evaluation was based on whole-body acceleration than on spatiotemporal parameters of the gait cycle. Here, we provide a more comprehensive analysis of this issue, using a Symmetry Index (SI) based on whole-body acceleration recorded on individuals aged 6 to 84 years old. Participants wore a single inertial sensor placed on the lower back and walked for 10 m at comfortable, slow and fast speeds. The SI was computed using the coefficient of correlation of whole-body acceleration measured at right and left gait cycles. Young Adults (19-35 years old) and Adults (36-50 years old) showed stable SI over the three speed conditions, while Children (6-12 years old), Teenagers (13-18 years old), Middle-Aged persons and Elderly (61-70 and 71-84 years old) exhibited lower SI values when walking at fast speed. Overall, this study confirms that whole-body gait symmetry is lower in Children and in Elderly persons over 60 years of age, showing, for the first time, that asymmetries appear also during teenage period and in Middle-Aged persons (51-60 years old).

The Interplay between Ghrelin and Microglia in Neuroinflammation: Implications for Obesity and Neurodegenerative Diseases.

Numerous studies have shown that microglia are capable of producing a wide range of chemokines to promote inflammatory processes within the central nervous system (CNS). These cells share many phenotypical and functional characteristics with macrophages, suggesting that microglia participate in innate immune responses in the brain. Neuroinflammation induces neurometabolic alterations and increases in energy consumption. Microglia may constitute an important therapeutic target in neuroinflammation. Recent research has attempted to clarify the role of Ghre signaling in microglia on the regulation of energy balance, obesity, neuroinflammation and the occurrence of neurodegenerative diseases. These studies strongly suggest that Ghre modulates microglia activity and thus affects the pathophysiology of neurodegenerative diseases. This review aims to summarize what is known from the current literature on the way in which Ghre modulates microglial activity during neuroinflammation and their impact on neurometabolic alterations in neurodegenerative diseases. Understanding the role of Ghre in microglial activation/inhibition regulation could provide promising strategies for downregulating neuroinflammation and consequently for diminishing negative neurological outcomes.

Protective role of vitamin D against oxidative stress in diabetic retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus. There is much evidence showing that a high level of mitochondrial overproduction of reactive oxygen species in the diabetic retina contributes in modifying cellular signalling and leads to retinal cell damage and finally to the development of DR pathogenesis. In the last few decades, it has been reported that vitamin D is involved in DR pathogenesis. Vitamin D, traditionally known as an essential nutrient crucial in bone metabolism, has also been proven to be a very effective antioxidant. It has been demonstrated that it modulates the production of advanced glycosylated end products, as well as several pathways including protein kinase C, the polyol pathway leading to the reduction of free radical formation. It prevents the translocation of nuclear factor kappa B, preventing the inflammatory response, acting as an immunomodulator, and modulates autophagy and apoptosis. In this review, we explore the molecular mechanisms by which vitamin D protects the eye from oxidative stress, in order to evaluate whether vitamin D supplementation may be useful to mitigate the deleterious effects of free radicals in DR.

Age differences in anticipatory and executory mechanisms of gait initiation following unexpected balance perturbations.

PURPOSE: An age-related decline in anticipatory postural mechanisms has been reported during gait initiation; however, it is unclear whether such decline may jeopardize whole-body stability following unexpected balance perturbations. This study aimed to compare young and older individuals' ability to generate postural responses and preserve stability in response to external waist perturbations delivered within gait initiation. METHODS: Ten young and ten older participants performed 10 gait initiation trials followed by 48 unperturbed and 12 perturbed trials in a random order. A stereophotogrammetric system and three force platforms were used to quantify mechanical parameters from the preparatory phase (e.g., timing and amplitude of postural adjustments) and from the stepping phase (e.g., step characteristics and dynamic stability). Activation patterns of lower leg muscles were determined by surface electromyography. RESULTS: Older participants responded to perturbation with lower increase in both magnitude (p < 0.001; η2p = 0.62) and duration (p = 0.001; η2p = 0.39) of preparatory parameters and soleus muscle activity (p < 0.001; η2p = 0.55), causing shorter (p < 0.001; η2p = 0.59) and lower (p < 0.001; η2p = 0.43) stepping, compared to young participants. Interestingly, young participants showed greater correlations between preparatory phase parameters and dynamic stability of the first step than older participants (average r of - 0.40 and - 0.06, respectively). CONCLUSION: The results suggest that young participants took more time than older to adjust the anticipatory biomechanical response to perturbation attempting to preserve balance during stepping. In contrast, older adults were unable to modify their anticipatory adjustments in response to perturbation and mainly relied on compensatory mechanisms attempting to preserve stability via a more cautious stepping strategy.

Use of a Single Wearable Sensor to Evaluate the Effects of Gait and Pelvis Asymmetries on the Components of the Timed Up and Go Test, in Persons with Unilateral Lower Limb Amputation.

The Timed Up and Go (TUG) test quantifies physical mobility by measuring the total performance time. In this study, we quantified the single TUG subcomponents and, for the first time, explored the effects of gait cycle and pelvis asymmetries on them. Transfemoral (TF) and transtibial (TT) amputees were compared with a control group. A single wearable inertial sensor, applied to the back, captured kinematic data from the body and pelvis during the 10-m walk test and the TUG test. From these data, two categories of symmetry indexes (SI) were computed: One SI captured the differences between the antero-posterior accelerations of the two sides during the gait cycle, while another set of SI quantified the symmetry over the three-dimensional pelvis motions. Moreover, the total time of the TUG test, the time of each subcomponent, and the velocity of the turning subcomponents were measured. Only the TF amputees showed significant reductions in each SI category when compared to the controls. During the TUG test, the TF group showed a longer duration and velocity reduction mainly over the turning subtasks. However, for all the amputees there were significant correlations between the level of asymmetries and the velocity during the turning tasks. Overall, gait cycle and pelvis asymmetries had a specific detrimental effect on the turning performance instead of on linear walking.

Time course of surface electromyography during walking of children with spastic cerebral palsy treated with botulinum toxin type A and its rehabilitation implications.

BACKGROUND: The timing of the effects of botulinum toxin A on spastic muscles is not yet fully clarified. The goal of this study was to follow the temporal changes of surface electromyographic activity of lower limb muscles during walking, after a therapeutic dose of botulinum toxin A injected into the calf muscles of children with spastic cerebral palsy. METHODS: A group of children with spastic equinus foot was administered botulinum toxin A into the gastrocnemius medialis and lateralis muscles. Surface electromyographic activity of the tibialis anterior, gastrocnemius medialis, rectus femoris and medial hamstrings, was recorded before botulinum toxin A injections and after 4, 8, and 16 weeks. Children walked on ground and on a treadmill at an incline of 0% and 12%. The area of electromyographic activity and the index of muscle co-contraction were calculated for specific segments of gait cycle. FINDINGS: Botulinum toxin A did not modify the speed of gait on ground. ANOVA showed significant differences in electromyography during the stance phase segments with a maximum decrease between 4 and 8 weeks' post botulinum toxin A and a full recovery at 16 weeks. A significant co-contraction of rectus femoris/gastrocnemius medialis, between 0 and 20% and 35-50% of the gait cycle, was observed from the 4th to the 8th week post- botulinum toxin A for both treadmill settings. INTERPRETATION: The temporal identification of deterioration/recovery of electromyographic activity as well as of muscle co-contractions, could be key elements in a rehabilitation program planning combined with botulinum toxin A.

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

BACKGROUND: Congenital disorders of glycosylation (CDG) are genetic diseases caused by impaired synthesis of glycan moieties linked to glycoconjugates. Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent CDG, is characterized by prominent neurological involvement. Gait disturbance is a major cause of functional disability in patients with PMM2-CDG. However, no specific gait assessment for PMM2-CDG is available. This study analyses gait-related parameters in PMM2-CDG patients using a standardized clinical assessment and instrumented gait analysis (IGA). RESULTS: Seven adult patients with a molecular diagnosis of PMM2-CDG were followed-up from February 2021 to December 2022 and compared to a group of healthy control (HC) subjects, matched for age and sex. Standardized assessment of disease severity including ataxia and peripheral neuropathy along with isometric muscle strength and echo-biometry measurements at lower limbs were performed. IGA spatiotemporal parameters were obtained by means of a wearable sensor in basal conditions. PMM2-CDG patients displayed lower gait speed, stride length, cadence and symmetry index, compared to HC. Significant correlations were found among the used clinical scales and between disease severity (NCRS) scores and the gait speed measured by IGA. Variable reduction of knee extension strength and a significant decrease of lower limb muscle thickness with conserved echo intensity were found in PMM2-CDG compared to HC. CONCLUSIONS: The study elucidates different components of gait disturbance in PMM2-CDG patients and shows advantages of using wearable sensor-based IGA in this frame. IGA parameters may potentially serve as quantitative measures for follow-up or outcome quantification in PMM2-CDG.

Comparison of Vitamin D and Resveratrol Performances in COVID-19.

Over the last few years, we have experienced the infection generated by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) often resulting in an exaggerated immune reaction and systemic inflammation. The preferred treatments against SARS-CoV-2 were those that mitigated immunological/inflammatory dysfunction. A variety of observational epidemiological studies have reported that vitamin D deficiency is often a crucial factor in many inflammatory diseases and autoimmune diseases, as well as the susceptibility to contract infectious diseases, including acute respiratory infections. Similarly, resveratrol regulates immunity, modifying the gene expression and the release of proinflammatory cytokines in the immune cells. Therefore, it plays an immunomodulatory role that can be beneficial in the prevention and development of non-communicable diseases associated with inflammation. Since both vitamin D and resveratrol also act as immunomodulators in inflammatory pathologies, many studies have paid particular attention to an integrated treatment of either vitamin D or resveratrol in the immune reaction against SARS-CoV-2 infections. This article offers a critical evaluation of published clinical trials that have examined the use of vitamin D or resveratrol as adjuncts in COVID-19 management. Furthermore, we aimed to compare the anti-inflammatory and antioxidant properties linked to the modulation of the immune system, along with antiviral properties of both vitamin D and resveratrol.

Balance impairment in cerebrotendinous xanthomatosis: Ankle strategy deficit. A case study.

BACKGROUND: Cerebrotendinous xanthomatosis is a rare autosomal-recessive lipid storage disorder causing an elevation in cholestanol and cholesterol levels and their deposition in the central nervous system and tendons with consequent posture and gait disturbances. METHODS: This report shows the case of a 36-year-old male affected by Cerebrotendinous xanthomatosis with static and dynamic instability. We aimed to provide an instrumented quantification of quiet upright standing using a piezoelectric force platform measuring the variations of center of pressure with the foot position 10 cm and 20 cm apart or extra-rotated with an opening angle of 30°, with eyes open or closed. The area of center of pressure and the length of its trajectory in the anterior-posterior and medial-lateral directions were computed. The temporal variability of center of pressure was evaluated by means of the Root Mean Square. FINDINGS: In comparison with a control group, the area, the trajectory length of center of pressure in anterior-posterior and medial-lateral directions and the temporal variability increased in all static conditions. Intra-patient comparison showed that foot position 10 cm apart was the position that most influenced stability causing a marked worsening of area and trajectory length of center of pressure in both anterior-posterior and medial-lateral directions, particularly for the eyes closed condition. INTERPRETATION: We found a large static instability due to internal neural and biomechanical constraints causing an insufficiency of ankle strategy. A physical therapy program based on instrumented proprioceptive exercises is to be implemented to teach the use of a hip strategy.

The Developmental Autism Early Screening (DAES): A Novel Test for Screening Autism Spectrum Disorder.

This study was undertaken to set a novel developmental screening test for autism spectrum disorder (ASD) using the Griffiths Scales of Child Development (Griffith III) (Green et al., 2016; Stroud et al., 2016), in order to intercept the early atypical developmental patterns indicating ASD risk in the first 3 years of age. An observational and interactive ASD screener, the Developmental Autism Early Screening (DAES), was developed by detecting Griffiths III items differentiating toddlers with ASD risk from those with global developmental delay (DD) or neurotypical development. The DAES was validated with ASD-specific diagnostic instruments (ADOS-2) and the cut-off score based on sensitivity, specificity and positive predictive value that best differentiates between ASD and non-ASD children was identified. We enrolled a total sample of 297 subjects, including children at risk for ASD or DD and neurotypical children. At a cut-off score of 12.5, the DAES had a sensitivity of 93%, specificity of 98.4%, positive predictive value of 96.3% and negative predictive value of 96.9% for identifying children at risk for ASD from non-ASD participants (DD/neurotypical children). The DAES total score correlated significantly with the ADOS-2 calibrated severity scores (CSS) (R = 0.53, p < 0.001). Three ASD risk ranges were identified according to DAES total and ADOS-2 CSS: Little-to-no risk (CSS: 1-3, DAES: 1-7); Mild-to-moderate risk (CSS: 4-5, DAES: 8-14); Moderate-to-severe risk (CSS: 6-10, DAES ≥ 15). The DAES provides a direct approach based on developmental profiles to stratify risk for ASD in early childhood ensuring at risk children the most appropriate diagnostic procedures and targeted intervention.

Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health.

Skeletal muscle dysfunction is frequently associated with chronic obstructive pulmonary disease (COPD), which is characterized by a permanent airflow limitation, with a worsening respiratory disorder during disease evolution. In COPD, the pathophysiological changes related to the chronic inflammatory state affect oxidant-antioxidant balance, which is one of the main mechanisms accompanying extra-pulmonary comorbidity such as muscle wasting. Muscle impairment is characterized by alterations on muscle fiber architecture, contractile protein integrity, and mitochondrial dysfunction. Exogenous and endogenous sources of reactive oxygen species (ROS) are present in COPD pathology. One of the endogenous sources of ROS is represented by mitochondria. Evidence demonstrated that vitamin D plays a crucial role for the maintenance of skeletal muscle health. Vitamin D deficiency affects oxidative stress and mitochondrial function influencing disease course through an effect on muscle function in COPD patients. This review will focus on vitamin-D-linked mechanisms that could modulate and ameliorate the damage response to free radicals in muscle fibers, evaluating vitamin D supplementation with enough potent effect to contrast mitochondrial impairment, but which avoids potential severe side effects.

Impact of Lung Microbiota on COPD.

There is a fine balance in maintaining healthy microbiota composition, and its alterations due to genetic, lifestyle, and environmental factors can lead to the onset of respiratory dysfunctions such as chronic obstructive pulmonary disease (COPD). The relationship between lung microbiota and COPD is currently under study. Little is known about the role of the microbiota in patients with stable or exacerbated COPD. Inflammation in COPD disorders appears to be characterised by dysbiosis, reduced lung activity, and an imbalance between the innate and adaptive immune systems. Lung microbiota intervention could ameliorate these disorders. The microbiota's anti-inflammatory action could be decisive in the onset of pathologies. In this review, we highlight the feedback loop between microbiota dysfunction, immune response, inflammation, and lung damage in relation to COPD status in order to encourage the development of innovative therapeutic goals for the prevention and management of this disease.

Is the Power Spectrum of Electromyography Signal a Feasible Tool to Estimate Muscle Fiber Composition in Patients with COPD?

A greater proportion of glycolytic muscle fibers is a manifestation of skeletal muscle dysfunction in Chronic Obstructive Pulmonary Disease (COPD). Here, we propose to use the spectral analysis of the electromyographic signal as a non-invasive approach to investigate the fiber muscle composition in COPD. We recorded the electromyographic activity of Rectus Femoris (RF), Vastus Lateralis (VL), Vastus Medialis (VM) and Biceps Femoris (BF) muscles, in ten patients and ten healthy individuals, during non-fatiguing, flexion-extension leg movements. The mean (MNF) and median frequencies (MDF) were calculated, and the most common profiles of electromyographic power spectrum were characterized by using the principal component analysis. Frequency parameters showed higher values in patients with COPD than in the control group for the RF (+25% for MNF; +21% for MNF), VL (+16% for MNF; 16% for MNF) and VM (+22% for MNF; 22% for MNF) muscles during the extension movements and for the BF (+26% for MNF; 34% for MNF) muscle during flexion movements. Spectrum profiles of the COPD patients shifted towards the higher frequencies, and the changes in frequency parameters were correlated with the level of disease severity. This shift of frequencies may indicate an increase in glycolytic muscle fibers in patients with COPD. These results, along with the non-fatigable nature of the motor task and the adoption of a non-invasive method, encourage to use electromyographic spectral analysis for estimating muscle fiber composition in patients with COPD.

Impact of chronic obstructive pulmonary disease on passive viscoelastic components of the musculoarticular system.

Chronic obstructive pulmonary disease (COPD) produces skeletal muscle atrophy and weakness, leading to impairments of exercise performance. The mechanical work needed for movement execution is also provided by the passive tension developed by musculoarticular connective tissue. To verify whether COPD affects this component, the passive viscoelastic properties of the knee joint were evaluated in 11 patients with COPD and in 11 healthy individuals. The levels of stiffness and viscosity were assessed by means of the pendulum test, consisting in a series of passive leg oscillations. In addition, to explore the contribution of passive tension in the mechanical output of a simple motor task, voluntary leg flexion-extension movements were performed. Patients with COPD showed a statistically significant reduction in stiffness and viscosity compared to controls. Voluntary execution of flexion-extension movements revealed that the electromyographic activity of the Rectus Femoris and Biceps Femoris was lower in patients than in controls, and the low viscoelastic tension in the patients conditioned the performance of active movements. These results provide novel insights on the mechanism responsible for the movement impairments associated with COPD.

Processing of limb kinematics in the interpositus nucleus.

Neural representations of limb movement kinematic parameters are common among central nervous system structures involved in motor control, such as the interpositus nucleus of the cerebellum. Much experimental evidence indicates that neurons in the interpositus may encode limb kinematic parameters both during active, voluntary actions and during limb motion imposed passively, which entrains only sensory afferents. With respect to the sensory processing of information related to movement kinematics, we show that interpositus neuronal activity can parse out the directional from the scalar component (i.e., the movement speed) of the velocity vector. Moreover, a differential role for the anterior and posterior portion of interpositus in encoding these parameters emerged from these data, since the activity of the posterior interpositus was specifically associated to changes of movement speed. Limb movement representations in the interpositus nucleus may be instrumental for the control of goal-directed movements such as shaping hand during grasping or precise foot placement during gait. Finally, we discuss the idea that sensory information about the movement kinematics contribute to both feedback and anticipatory processes for limb movement control.

Representation of movement velocity in the rat's interpositus nucleus during passive forelimb movements.

The interpositus nucleus (IN) receives a large amount of sensory information from the limbs and, in turn, elaborates signals for movement control. In this paper, we tried to gather evidence on the possibility that neurons in the IN may elaborate sensory representations of the forelimb kinematics and, particularly, of the movement velocity vector. For this purpose, the forepaw of anesthetized rats was attached to a computer-controlled robot arm displaced passively along two types of trajectories (circular and figure eight), with the limb joints unconstrained. The firing activity of single cells was recorded and related to limb position and the two components of the movement velocity vector, namely, movement speed and direction. By using multiple regression analysis, we found that 12 out of 85 (14%) neurons were modulated by position, 18 out of 85 (21%) neurons were modulated by direction, 24 out of 85 (28%) neurons were modulated by movement speed, and 31 out of 85 (37%) neurons were sensitive to the full movement velocity vector. Most of the neurons modulated only by the speed component of the velocity vector (19 out of 24) were located in the posterior portion of the IN, whereas neurons in the anterior portion were mostly related to both components of the velocity vector. These results suggest that sensory information related to whole-limb movement velocity may be encoded by the IN, indicating also that the posterior interpositus may preferentially represent movement speed.

Effects of Functional Electrical Stimulation Cycling of Different Duration on Viscoelastic and Electromyographic Properties of the Knee in Patients with Spinal Cord Injury.

The benefits of functional electrical stimulation during cycling (FES-cycling) have been ascertained following spinal cord injury. The instrumented pendulum test was applied to chronic paraplegic patients to investigate the effects of FES-cycling of different duration (20-min vs. 40-min) on biomechanical and electromyographic characterization of knee mobility. Seven adults with post-traumatic paraplegia attended two FES-cycling sessions, a 20-min and a 40-min one, in a random order. Knee angular excursion, stiffness and viscosity were measured using the pendulum test before and after each session. Surface electromyographic activity was recorded from the rectus femoris (RF) and biceps femoris (BF) muscles. FES-cycling led to reduced excursion (p < 0.001) and increased stiffness (p = 0.005) of the knee, which was more evident after the 20-min than 40-min session. Noteworthy, biomechanical changes were associated with an increase of muscle activity and changes in latency of muscle activity only for 20-min, with anticipated response times for RF (p < 0.001) and delayed responses for BF (p = 0.033). These results indicate that significant functional changes in knee mobility can be achieved by FES-cycling for 20 min, as evaluated by the pendulum test in patients with chronic paraplegia. The observed muscle behaviour suggests modulatory effects of exercise on spinal network aimed to partially restore automatic neuronal processes.

Relationship between accuracy and complexity when learning underarm precision throwing.

Learning precision ball throwing was mostly studied to explore the early rapid improvement of accuracy, with poor attention on possible adaptive processes occurring later when the rate of improvement is reduced. Here, we tried to demonstrate that the strategy to select angle, speed and height at ball release can be managed during the learning periods following the performance stabilization. To this aim, we used a multivariate linear model with angle, speed and height as predictors of changes in accuracy. Participants performed underarm throws of a tennis ball to hit a target on the floor, 3.42 m away. Two training sessions (S1, S2) and one retention test were executed. Performance accuracy increased over the S1 and stabilized during the S2, with a rate of changes along the throwing axis slower than along the orthogonal axis. However, both the axes contributed to the performance changes over the learning and consolidation time. A stable relationship between the accuracy and the release parameters was observed only during S2, with a good fraction of the performance variance explained by the combination of speed and height. All the variations were maintained during the retention test. Overall, accuracy improvements and reduction in throwing complexity at the ball release followed separate timing over the course of learning and consolidation.