Current therapies for Parkinson’s disease (PD) are palliative, of which the levodopa/carbidopa therapy remains the primary choice but is unable to modulate the progression of neurodegeneration. Due to the complication of such a multifactorial disorder and significant limitations of the therapy, numerous genetic approaches have been proved effective in finding out genes and mechanisms implicated in this disease. Following the observation of a higher frequency of PD in Gaucher’s disease (GD), a lysosomal storage condition, mutations of glycosylceramidase beta (GBA) encoding glucocerebrosidase (GCase) have been shown to be involved and have been explored in the context of PD. GBA mutations are the most common genetic risk factor of PD. Various studies have revealed the relationships between PD and GBA gene mutations, facilitating a better understanding of this disorder. Various hypotheses delineate that the pathological mutations of GBA minimize the enzymatic activity of GCase, which affects the proliferation and clearance of α-synuclein; this affects the lysosomal homeostasis, exacerbating the endoplasmic reticulum stress or encouraging the mitochondrial dysfunction. Identification of the pathological mechanisms underlying the GBA-associated parkinsonism (GBA + PD) advances our understanding of PD. This review based on current literature aims to elucidate various genetic and clinical characteristics correlated with GBA mutations and to identify the numerous pathological processes underlying GBA + PD. We also delineate the therapeutic strategies to interfere with the mutant GCase function for further improvement of the related α-synuclein–GCase crosstalks. Moreover, the various therapeutic approaches such as gene therapy, chaperone proteins, and histone deacetylase inhibitors for the treatment of GBA + PD are discussed.
It is considered that COVID-19’s pandemic expansion is responsible for the particular increase in deaths, especially among the population with comorbidities. The health system is often overwhelmed by the large number of cases of patients addressing it, by the regional limitation of funds, and by the gravity of cases at subjects suffering from this pathology. Several associated conditions including diabetes, cardiovascular illnesses, obesity, persistent lung condition, neurodegenerative diseases, etc., increase the mortality risk and hospitalization of subjects suffering from COVID-19. The rapid identification of patients with increased risk of death from the SARS-CoV-2 virus, the stratification in accordance with the risk and the allocation of human, financial, and logistical resources in proportion must be a priority for health systems worldwide.
The prolonged immobilization associated with COVID-19 infection and the restrictions imposed by the pandemic have determined major changes in physical activity and eating habits, with a negative impact on physical performance. This study monitored non-pharmacological interventions (diet therapy and probiotics) in managing sarcopenia for patients with recent SARS-CoV-2 history (14 days). A prospective study was performed on 200 patients (between December 2020–December 2021), with SPPB score < 9, randomly divided into: Group K—DP (93 patients) with dietary therapy (protein 1.2–1.5 g/kg) and probiotics for two months; and Group K—non-DP (107 patients) without diet therapy and probiotics. All patients were included in a specific physical training program (40 min), three sessions per week. Skeletal muscle index (SMI), serum albumin, and hemoglobin were determined. The SMI was initially low for both groups without significant statistical differences (6.5 ± 0.52 kg/m2 for Group K—non-DP vs. 6.7 ± 0.57 Kg/m2 for Group K—DP, p = 0.135). After two months, significant difference between initial and final SMI values was determined for Group K—DP (6.92 ± 0.50 kg/m2 vs. 6.77 ± 0.56 kg/m2, p = 0.048). In Group K—DP, at end of study, were more patients with normal SMI (n = 32 → N = 70) values (p < 0.001) and fewer sarcopenia patients (p < 0.001). The initial serum albumin means values in the two groups (Group K—non-DP, 4.17 ± 1.04 g/dL, and Group K—DP, 3.95 ± 0.98 g/dL) were not statistically significantly different (p = 0.122). The hemoglobin level improved significantly following a hyper protein diet enriched with pro-biotics (p = 0.003). Diet therapy, consisting of increased protein intake and specific probiotics and specific physical therapy, demonstrated superiority in improving the functional status of patients with recent COVID-19 infection.
Background and Objectives: Quarantine, isolation and bed rest associated with COVID-19 infection favored the loss of muscle and bone mass, especially in elderly patients. The current study aims to compare the presence of sarcopenia and osteoporosis in patients with a recent (one month) history of SARS-CoV-2 infection versus the general population. Materials and Methods: A cross-sectional study was conducted in which 157 patients were enrolled, divided into two groups, comparable in structure. The COVID-19 group (group C) consisted of 86 patients who were diagnosed with SARS-CoV-2 respiratory infection within the last 30 days. The non-COVID-19 group (group NC) consists of 71 patients who had no clinical signs of respiratory infection and were not quarantined/hospitalized in the last 3 months. Muscle strength, incidence of sarcopenia (using SARC-F score) and osteoporosis (DEXA determination) and physical performance (SPPB score) in the two groups were assessed and compared. Results: No statistically significant differences were found between the SPPB scores of the C group versus the NC group. Statistically significant differences were found in the evaluation of three parameters included in the SARC-F score. Patients in the C group had difficulties in standing up from a chair (p = 0.009) and climbing stairs (p = 0.030) due to lower muscle strength (p = 0.002) compared with patients in the NC group. No correlation of the SARC F and SPPB scores with the T score values obtained by osteo-densitometry was found. Conclusions: The sudden and significant reduction in physical activity, through various measures taken in the general population during the pandemic, led to an increased incidence of sarcopenia, both in patients who did not have COVID-19 infection and among those quarantined/hospitalized for this condition.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is responsible for generating a global effort to discover urgent therapeutic solutions to limit the human damage caused by COVID-19. In the period of April to June 2020, 105 patients diagnosed with COVID-19 met the conditions for inclusion in the present study. They were treated with antiviral therapy according to local guidelines: D group (53 cases), treated with darunavir/ritonavir (DRV/r); and K group (52 cases), treated with lopinavir/ritonavir (LPV/r). Patients from the K group required 7.5 days of hospitalization less compared to those from the D group (P<0.001). The blood oxygen saturation values recorded in the groups were statistically different [K group (94.02±3.12%) vs. D group (92.13±4.24%), P=0.010]. The percentage of patients with unsatisfactory clinical evolution were non-significantly higher in the D group compared with the K group [20 (37.74%) vs. 12 (23.08%), P= 0.157]. We did not note statistically significant differences between the two groups tracked considering the values for the Brescia-COVID Respiratory Severity Scale (BCRSS) of the patients with unsatisfactory clinical evolution, nor of the chest CT' evolution after 10 days of therapy. We did not register significant adverse effects after antiviral therapy in the two groups. Antiviral therapy with LPV/r had some favorable results compared to DRV/r in patients with COVID-19. Both therapies were well tolerated.
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