The Involvement of Neuroinflammation in the Onset and Progression of Parkinson's Disease.

Parkinson's disease is a neurodegenerative disease exhibiting the fastest growth in incidence in recent years. As with most neurodegenerative diseases, the pathophysiology is incompletely elucidated, but compelling evidence implicates inflammation, both in the central nervous system and in the periphery, in the initiation and progression of the disease, although it is not yet clear what triggers this inflammatory response and where it begins. Gut dysbiosis seems to be a likely candidate for the initiation of the systemic inflammation. The therapies in current use provide only symptomatic relief, but do not interfere with the disease progression. Nonetheless, animal models have shown promising results with therapies that target various vicious neuroinflammatory cascades. Translating these therapeutic strategies into clinical trials is still in its infancy, and a series of issues, such as the exact timing, identifying biomarkers able to identify Parkinson's disease in early and pre-symptomatic stages, or the proper indications of genetic testing in the population at large, will need to be settled in future guidelines.

Cholesterol Management in Neurology: Time for Revised Strategies?

Statin therapy has been extensively evaluated and shown to reduce the incidence of new or recurrent vascular events, ischemic stroke included. As a consequence, each published guideline pushes for lower low-density cholesterol levels in the population at large, recommending increased statin doses and/or adding new cholesterol-lowering molecules. Neurologists find it sometimes difficult to apply these guidelines, having to confront situations such as (1) ischemic strokes, mainly cardioembolic ones, in patients with already low LDL-cholesterol levels; (2) myasthenic patients, whose lifespan has been extended by available treatment, and whose age and cholesterol levels put them at risk for ischemic stroke; (3) patients with myotonic dystrophy, whose disease often associates diabetes mellitus and heart conduction defects, and in whom blood cholesterol management is also not settled. As such, further trials are needed to address these issues.

Stem Cell- and Cell-Based Therapies for Ischemic Stroke.

Stroke is the second cause of disability worldwide as it is expected to increase its incidence and prevalence. Despite efforts to increase the number of patients eligible for recanalization therapies, a significant proportion of stroke survivors remain permanently disabled. This outcome boosted the search for efficient neurorestorative methods. Stem cells act through multiple pathways: cell replacement, the secretion of growth factors, promoting endogenous reparative pathways, angiogenesis, and the modulation of neuroinflammation. Although neural stem cells are difficult to obtain, pose a series of ethical issues, and require intracerebral delivery, mesenchymal stem cells are less immunogenic, are easy to obtain, and can be transplanted via intravenous, intra-arterial, or intranasal routes. Extracellular vesicles and exosomes have similar actions and are easier to obtain, also allowing for engineering to deliver specific molecules or RNAs and to promote the desired effects. Appropriate timing, dosing, and delivery protocols must be established, and the possibility of tumorigenesis must be settled. Nonetheless, stem cell- and cell-based therapies for stroke have already entered clinical trials. Although safe, the evidence for efficacy is less impressive so far. Hopefully, the STEP guidelines and the SPAN program will improve the success rate. As such, stem cell- and cell-based therapy for ischemic stroke holds great promise.

The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer's Disease: Therapeutic Implications and Future Perspectives.

Alzheimer's disease (AD), the most common form of dementia, has increasing incidence, increasing mortality rates, and poses a huge burden on healthcare. None of the currently approved drugs for the treatment of AD influence disease progression. Many clinical trials aiming at inhibiting amyloid plaque formation, increasing amyloid beta clearance, or inhibiting neurofibrillary tangle pathology yielded inconclusive results or failed. Meanwhile, research has identified many interlinked vicious cascades implicating oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, and has pointed to novel therapeutic targets such as improving mitochondrial bioenergetics and quality control, diminishing oxidative stress, or modulating the neuroinflammatory pathways. Many novel molecules tested in vitro or in animal models have proven efficient, but their translation into clinic needs further research regarding appropriate doses, delivery routes, and possible side effects. Cell-based therapies and extracellular vesicle-mediated delivery of messenger RNAs and microRNAs seem also promising strategies allowing to target specific signaling pathways, but need further research regarding the most appropriate harvesting and culture methods as well as control of the possible tumorigenic side effects. The rapidly developing area of nanotechnology could improve drug delivery and also be used in early diagnosis.

Rice bran, an off-shoot to newer therapeutics in neurological disorders.

Normal brain functioning involves the interaction of interconnected molecular and cellular activities, which appear to alter normal to abnormal brain functioning when worsened, contributing to the emergence of neurological disorders. There are currently millions of people who are living with brain disorders globally and this will rise if suitable prevention strategies are not explored. Nutraceutical intended to treat numerous health goals with little adverse effect possible together can be more beneficial than pharmaceutical monotherapy for fostering balanced brain functioning. Nutraceutical provides a specific composition of effective macronutrients and micronutrients that are difficult to synthesize in the laboratory. Numerous elements of rice fibers in rice bran are characterized as natural anti-oxidant and having potential anti-inflammatory activity. The rice bran captures interest among the researchers as it is widespread, affordable, and rich in nutrients including protein, fat, carbohydrates, bioactive components, and dietary fiber. This review covers the neuroprotective multiplicity of rice bran and its constituents to deter pathological conditions of the brain and to facilitate balanced brain functioning at the same time.

Efficiency of antiviral treatment in COVID-19.

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.

Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.

Obesity or overweight are not superficial problems, constituting a pressing issue. The obesity index has almost tripled since 1975, which is an alarming state. Most of the individuals are currently becoming overweight or have inappropriate body mass index (BMI) conditions. Obesity is characterized by increased fat accumulation and thus poses a higher health risk. There is increased size and volume of fat cells in the body, which usually accounts for obesity. Many investigations have been carried out in this area, such as behavioral improvements, dietary changes, chemical involvements, etc., but presently no such goals are established to manage these health concerns. Based on previous literature reports and our interpretation, the current review indicates the involvement of various transcriptional and transporter functions in modifying the above-mentioned health conditions. Various transcriptional factors such as Forkhead box O1 (FoxO1) impart a significant effect on the physiology and pathology of metabolic dysfunction such as obesity. FoxO1 plays a dual role whether in the progression or suppression of metabolic processes depending on its targets. Thus, in the current study, will be discussed the dual role of FoxO1 in metabolic conditions (such as obesity), also summarizing the role of various other transcriptional factors involved in obesity.

Exploring the multifocal role of phytochemicals as immunomodulators.

A well-functioning immune system of the host body plays pivotal role in the maintenance of ordinary physiological and immunological functions as well as internal environment. Balanced immunity enhances defense mechanism against infection, diseases and unwanted pathogens to avoid hypersensitivity reactions and immune related diseases. The ideal immune responses are the results of corrective interaction between the innate immune cells and acquired components of the immune system. Recently, the interest towards the immune system increased as significant target of toxicity due to exposure of chemicals, drugs and environmental pollutants. Numerous factors are involved in altering the immune responses of the host such as sex, age, stress, malnutrition, alcohol, genetic variability, life styles, environmental-pollutants and chemotherapy exposure. Immunomodulation is any modification of immune responses, often involved induction, amplification, attenuation or inhibition of immune responses. Several synthetic or traditional medicines are available in the market which promptly have many serious adverse effects and create pathogenic resistance. Phytochemicals are naturally occurring molecules, which significantly play an imperative role in modulating favorable immune responses. The present review emphasizes on the risk factors associated with alterations in immune responses, and immunomodulatory activity of phytochemicals specifically, glycosides, alkaloids, phenolic acids, flavonoids, saponins, tannins and sterols and sterolins.

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients.

While the most common manifestations associated with rheumatoid arthritis (RA) are synovial damage and inflammation, the systemic effects of this autoimmune disorder are life-threatening, and are prevalent in 0.5-1% of the population, mainly associated with cardiovascular disorders (CVDs). Such effects have been instigated by an altered lipid profile in RA patients, which has been reported to correlate with CV risks. Altered lipid paradox is related to inflammatory burden in RA patients. The review highlights general lipid pathways (exogenous and endogenous), along with the changes in different forms of lipids and lipoproteins in RA conditions, which further contribute to elevated risks of CVDs like ischemic heart disease, atherosclerosis, myocardial infarction etc. The authors provide a deep insight on altered levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in RA patients and their consequence on the cardiovascular health of the patient. This is followed by a detailed description of the impact of anti-rheumatoid therapy on the lipid profile in RA patients, comprising DMARDs, corticosteroids, anti-TNF agents, anti-IL-6 agents, JAK inhibitors and statins. Furthermore, this review elaborates on the prospects to be considered to optimize future investigation on management of RA and treatment therapies targeting altered lipid paradigms in patients.

Risk Factors Associated with Recurrent Clostridioides difficile Infection.

Clostridioides difficile (CD) is responsible for nosocomial diarrhea syndrome with possible severe progression. Recurrence of the disease induces higher health system costs, as well as exposes patients to additional health risks. Patients with recurrence of this disease are difficult to identify, so the purpose of this study is to quantify various demographic, clinical, and treatment factors that could prevent further progression to recurrence of the disease. In the period 2018-2019, about 195 patients were diagnosed with more than one episode of CDI in the three months following the first episode. The recurrence rate for CDI was 53.84% (60.95% for one episode and 39.05% for multiple episodes). Most commonly afflicted were 60-69-year-old patients, or those with higher Charlson Comorbidity Index (CCI). Multiple analyses associated cardiovascular (odds ratios (OR) = 3.02, 95% confidence intervals (CI) = 1.23-7.39, p = 0.015), digestive (OR = 3.58, 95% CI = 1.01-12.63, p = 0.047), dementia (OR = 3.26, 95% CI = 1.26-8.41, p = 0.014), immunosuppressive (OR = 3.88, 95% CI = 1.34-11.21, p = 0.012) comorbidities with recurrences. Risk factor identification in the first episode of CDI could lead to the implementation of treatment strategies to improve the patients' quality of life affected by this disease.

Acute Coronary Syndromes in Chronic Kidney Disease: Clinical and Therapeutic Characteristics.

Background and Objectives: This study evaluated the clinical characteristics of the acute coronary syndromes (ACS) in chronic kidney disease (CKD) patients and established prognostic values of the biomarkers and echocardiography. Materials and Methods: 273 patients admitted to the cardiology department of the Clinical County Emergency Hospital of Oradea, Romania, with ACS diagnosis were studied. Two study groups were formed according to the presence of CKD (137 patients with ACS + CKD and 136 with ACS without CKD). Kidney Disease: Improving Global Outcomes (KDIGO) threshold was used to assess the stages of CKD. Results: Data regarding the medical history, laboratory findings, biomarkers, echocardiography, and coronary angiography were analysed for both groups. ACS parameters were represented by ST-segment elevation myocardial infarction (STEMI), which revealed a greater incidence in subjects without CKD (43.88%); non-ST-segment elevation myocardial infarction (NSTEMI), characteristic for the CKD group (28.47%, with statistically significance p = 0.04); unstable angina and myocardial infarction with nonobstructive coronary arteries (MINOCA). Diabetes mellitus, chronic heart failure, previous stroke, and chronic coronary syndrome were more prevalent in the ACS + CKD group (56.93%, p < 0.01; 41.61%, p < 0.01; 18.25%, p < 0.01; 45.26%, p < 0.01). N-terminal pro b-type natriuretic peptide (NT-proBNP) was statistically higher (p < 0.01) in patients with CKD; Killip class 3 was evidenced more frequently in the same group (p < 0.01). Single-vessel coronary artery disease (CAD) was statistically more frequent in the ACS without CKD group (29.41%, p < 0.01) and three-vessel CAD or left main coronary artery disease (LMCA) were found more often in the ACS + CKD group (27.01%, 14.6%). Conclusions: Extension of the CAD in CKD subjects revealed an increased prevalence of the proximal CAD, and the involvement of various coronary arteries is characteristic in these patients. Biomarkers and echocardiographic elements can outline the evolution and outcomes of ACS in CKD patients.

Epidemiology of human giardiasis in Romania: A 14 years survey.

Giardia spp. is the most common intestinal protozoan (causing gastrointestinal illness) and the most frequent cause of parasitic gastroenteritis in humans and animals worldwide. The aim of this study was to highlight new data in a specific area regarding clinical presentation and epidemiological prevalence over a long period of time. Patients (a total number of 54,623 patients) admitted in a tertiary center for infectious diseases serving a county for a period of 14 years were tested for infection with Giardia. Positive cases were recorded through analyzing the clinical complaints, the month of incidence and the demographic area from which the patients came from. Longitudinal trends have been evaluated. The incidence of giardiasis among the tested patients was 4.47%. A decreasing trend was observed regarding the annual incidence. Patients between the ages of 15 and 44 presented most commonly giardiasis, especially those from urban areas and women. The most common symptoms are loss of appetite (71.24%) and abdominal pain (69.07%). The highest monthly incidence was quoted in July (10.65%), August (10.49%) and June (10.20%). This epidemiological study allows a better knowledge of the infection with Giardia spp. It gives the long-term changes in demographic characteristics of the infected patients in a specific area and the monthly incidence.

Effects of combining modern recovery techniques with neurotrophic medication and standard treatment in stroke patients.

Stroke is the main cause of disability after age 65, leaving survivors with sequels that require care and recovery treatment lasting years. It is estimated that by the year 2030 this pathology will be leading cause of mortality. To determine the efficacy of Lokomat training combined with neurotrophic medication and balneo-physiotherapeutic treatment in rehabilitation of post-stroke patients, a prospective study of 3 parallel groups was conducted: Group I (n = 22) - Lokomat, balneo-physiotherapy, and Cerebrolysin; Group II (n = 18) - Lokomat associated with balneo-physiotherapy; and Group III (n = 30) - balneo-physiotherapy alone (Control group). Patients were evaluated physically, neurologically, and functionally, according to the evolution of their motor deficiency, spasticity, functional independence and health-related quality of life. Patient improvement is significantly better (p < 0.05) in the group with associated therapies, especially during the first 6 months. Evolution was significantly better in all groups at 12 months than initially (p < 0.05), for all studied parameters and with the best effects in Group I (the three therapies combined). Association of Lokomat training with neurotrophic factors and classic recovery techniques improves the rehabilitation process in stroke patients.

Effects of the Hormone Replacement Therapy and of Soy Isoflavones on Bone Resorption in Postmenopause.

Postmenopausal osteoporosis is the most common form of osteoporosis and one of the major public health problems in developed countries. The prevalence of this condition, associated with the physiological stage of menopause, is continuously increasing. This study evaluated the effectiveness of soy isoflavones as compared to hormone replacement therapy (HRT) in low doses, on the prevention of postmenopausal osteoporosis, by determining bone mineral density (BMD) and urinary deoxypyridinoline (D-pyr) in physiological postmenopausal women. The study was conducted over a period of 12 months, on three parallel groups, which included a total of 325 postmenopausal women (HRT group: n = 95; phytoestrogens group: n = 124; control group: n = 106). At the one-year evaluation, we observed T-score normalization in a small number of cases (5.26%, 2.42% and 0.00%, respectively). The average values of D-Pyr decreased by 11.38% in the group treated with phytoestrogens (p < 0.05) and by 15.32% in the group that followed HRT (p < 0.05); it increased by 4.38% in the control group (p > 0.05). Both therapies have beneficial effects on bone metabolism, leading to a significant decrease in the evolution of bone resorption and there are no major differences between the efficacy of HRT and phytoestrogens in terms of the effects on BMD and bone resorption.