A pathophysiological model of gait captures the details of the impairment of pace/rhythm, variability and asymmetry in Parkinsonian patients at distinct stages of the disease

Locomotion in people with Parkinson’ disease (pwPD) worsens with the progression of disease, affecting independence and quality of life. At present, clinical practice guidelines recommend a basic evaluation of gait, even though the variables (gait speed, cadence, step length) may not be satisfactory for assessing the evolution of locomotion over the course of the disease. Collecting variables into factors of a conceptual model enhances the clinical assessment of disease severity. Our aim is to evaluate if factors highlight gait differences between pwPD and healthy subjects (HS) and do it at earlier stages of disease compared to single variables. Gait characteristics of 298 pwPD and 84 HS able to walk without assistance were assessed using a baropodometric walkway (GAITRite®). According to the structure of a model previously validated in pwPD, eight spatiotemporal variables were grouped in three factors: pace/rhythm, variability and asymmetry. The model, created from the combination of three factor scores, proved to outperform the single variables or the factors in discriminating pwPD from HS. When considering the pwPD split into the different Hoehn and Yahr (H&Y) stages, the spatiotemporal variables, factor scores and the model showed that multiple impairments of gait appear at H&Y stage 2.5, with the greatest difference from HS at stage 4. A contrasting behavior was found for the asymmetry variables and factor, which showed differences from the HS already in the early stages of PD. Our findings support the use of factor scores and of the model with respect to the single variables in gait staging in PD.

A Pathophysiological Model for COVID-19: Critical Importance of Transepithelial Sodium Transport upon Airway Infection

The Coronavirus Disease 2019 (COVID-19) pandemic remains a serious public health problem and will continue to be until effective drugs and/or vaccines are available. The rational development of drugs critically depends on our understanding of disease mechanisms, that is, the physiology and pathophysiology underlying the function of the organ targeted by the virus. Since the beginning of the pandemic, tireless efforts around the globe have led to numerous publications on the virus, its receptor, its entry into the cell, its cytopathic effects, and how it triggers innate and native immunity but the role of apical sodium transport mediated by the epithelial sodium channel (ENaC) during the early phases of the infection in the airways has received little attention. We propose a pathophysiological model that defines the possible role of ENaC in this process.

Pathophysiological model of indirect revascularization in rats with microangiopathy of limbs caused by experimental streptozocin diabetes

Despite the large number of publications, the model of experimental diabetes after the introduction of streptozotocin remains a subject of lively scientific debate. The purpose of this study was to develop a pathophysiological model of indirect revascularization in rats with microangiopathy of limbs caused by experimental streptozotocin diabetes. Experimental studies were carried out in a chronic experiment on 100 sexually mature Wistar rats weighing 180-250 g. The streptozotocin diabetes model used. After culling animals from increased resistance to pancreatotropic toxicity by the criterion of the absence of hyperglycemia, three experimental groups were formed: Group I (control) – rats with streptozotocin-induced angiopathy without treatment (n=10); II group – rats with streptozotocin-induced angiopathy treated with pentoxifylline (100 mg/kg IP for 10 days) for therapeutic purposes (n=25); III group – rats with streptozotocin-induced angiopathy, which together with the treatment were injected with platelet-rich plasma (in the right hind limb, once, with a volume of 0.2 ml, linearly, retrogradely, from two points) and pentoxifylline (100 mg/kg IP for 10 days) (n=25). The duration of the experiment was 110 days. We studied the level of glycemia, the state of microcirculation, and the degree of pathomorphological changes in the various study groups. Statistical processing was performed by non-parametric methods using software Statistica 10.0. The developed pathophysiological model of indirect revascularization with the introduction of pentoxifylline and plasma enriched with platelets in diabetic angiopathy is adequate to the needs of clinical physiology. It has been shown that the isolated administration of pentoxifylline is inferior to combined therapy by revascularizing activity. The results of the work may be an experimental justification for the feasibility of clinical application of the combination of pentoxifylline and platelets rich plasma in the treatment of diabetic angiopathy, as well as its use in prophylactic purposes in patients with diabetes mellitus.

Topographic diversity of structural connectivity in schizophrenia

The neurobiological heterogeneity of schizophrenia is widely accepted, but it is unclear how mechanistic differences converge to produce the observed phenotype. Establishing a pathophysiological model that accounts for both heterogeneity and phenotypic similarity is essential to inform stratified treatment approaches. In this cross-sectional diffusion tensor imaging (DTI) study, we recruited 77 healthy controls (HC), and 71 patients with DSM-IV diagnosis of schizophrenia (SCZ), and reconstructed the structural connectivity of 90 brain regions covering entire cerebral cortex. We first confirmed the heterogeneity in structural connectivity by showing a reduced inter-individual similarity in SCZ compared with HC. Moreover, we found it was not possible to cluster patients into subgroups with shared patterns of dysconnectivity, indicating a high degree of mechanistic divergence in schizophrenia. Instead of the strength of connectivity between any particular brain regions, we investigated the diversity (or statistically, the variance) of the topographic distribution of the strength was reduced. HC had higher topographic diversity in whole brain structural connectivity compared to the patient group(P = 2 × 10−6, T = 4.96, Cohen′S d = 0.87). In 62 of the 90 brain regions, the topographic diversity was significantly reduced in patients compared to controls after FDR correction (<0.05). When topographic diversity was used as a discriminant feature for classification between patients and controls, we significantly (P = 4.29 × 10−24) improved the classification accuracy to 79.6% (sensitivity 78.3%, specificity 81.3%). This finding suggests highly individualized pattern of structural dysconnectivity underlying the heterogeneity of schizophrenia converges to a convergent common pathway as reduced topographic diversity for the clinical construct of the disease.