Protective effects of licofelone on scopolamine-induced spatial learning and memory impairment by enhancing parkin-dependent mitophagy and promotion of neural regeneration and in adult mice.

Inhibition of COX and LOX could contribute to memory formation and prevention of neurodegeneration, by alleviation of neuroinflammation and improvement of mitochondrial homeostasis. We aimed to assess the effect of licofelone, a dual COX and 5-LOX inhibitor on memory formation, neural apoptosis, neural regeneration, and mitophagy in acute and chronic dosages, given that licofelone could regulate nitric oxide levels. Y-maze and Passive Avoidance tests were used to evaluate memory function in NMRI mice using the EthoVision setting, following scopolamine administration (1 mg/kg, i.p.) as an acute amnestic drug. Hippocampi were used to evaluate the levels of apoptosis via TUNEL assay, neural regeneration via immunohistochemistry method detecting doublecortin and nestin, and mitophagy via Western blot of mitophagy proteins Parkin and ATG5. While acute high-dose licofelone (20 mg/kg) could reverse amnestic effects of scopolamine in passive avoidance test (p = 0.0001), Chronic licofelone (10 mg/kg for 10 consecutive days) could improve performance in Y-maze (p = 0.0007). Molecular analysis revealed that the chronic form of the drug could enhance neural regeneration in CA1 and SGZ regions, reset mitophagy levels as much as the healthy state, and reduce apoptosis rate. Licofelone appears to show a desirable anti-amnestic profile in a low dose chronically; it is hence recommended for future clinical studies on the prevention of neuroinflammation and memory deficit.

The association of upper respiratory infections with neuro-radiological course and attack rate of multiple sclerosis: Results from a large prospective cohort.

Background: Although upper respiratory infections (URIs) are linked to multiple sclerosis (MS) attacks, SARS-COV2 has not been compared to URIs for attack rates. Objectives: This study aimed to evaluate the attack rate and the results of neuroimaging in MS patients with URIs caused by COVID-19 and non-COVID-19 infections (NC-URI). Methods: From May 2020 to April 2021, we followed 362 patients with relapsing-remitting MS in a prospective cohort design. Patients were monitored regularly every 12 weeks; an magnetic resonance imaging (MRI) scan was performed at enrollment and every time a relapse occurred. Poisson analysis was used to determine exacerbation rate ratios (RR) and the MRI parameters were tested using chi-square analysis. Results: 347 patients with an average age of 38 and a female ratio of 86% were included. A RR of 2.24 (p < 0.001) was observed for exacerbations during the at-risk period (ARP). Attacks related to COVID-19 (RR = 2.13, p = 0.001) and NC-URIs (RR = 2.39, p < 0.001) were comparable regarding the increased risk of exacerbation (p = 0.62). Exacerbations within or outside the ARP did not significantly alter the number of baseline GAD-enhancing lesions (p > 0.05 for both). Conclusion: COVID-19 has been shown to increase the risk of MS exacerbations, like other viral URIs.

Phenotype and genotype heterogeneity of PLA2G6-associated neurodegeneration in a cohort of pediatric and adult patients.

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6. METHODS: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach. RESULTS: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6. CONCLUSION: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype.

Reactive arthritis after Gam-COVID-Vac vaccination: A case report.

Although the safety and efficacy of vaccinations have been evaluated through clinical trials, medical experts and authorities are very interested in the reporting and investigation of adverse events following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunisation in the general public. This article reports about a 41-year-old man without a history of underlying diseases, complaining of continuous morning stiffness and acute discomfort in his left elbow joint, 20 days after taking the first dosage of Sputnik V. The case was extensively studied, and a possible diagnosis of reactive arthritis was made.

COVID-19 in Patients with Rheumatic Disease Using Immunomodulatory Drugs: Imaging Findings and Predictors of Hospitalization.

Introduction: SARS-CoV-2 causes more severe symptoms in most chronic diseases, and rheumatic disease is no exception. This study aims to investigate whether there is an association between the use of immunomodulatory medications, including conventional disease-modifying agents (csDMARDs), glucocorticoids, and biologic DMARDs, and outcomes such as hospitalization and lung involvement in patients with rheumatic disease with COVID-19. Methods: We performed a cross-sectional study on 177 COVID-19 cases with rheumatologic diseases using immunomodulatory drugs as their regular treatment. All patients were evaluated regarding their initial chest computed tomography (CT) scan, COVID-19 symptoms, and comorbidities. We ran predictive models to find variables associated with chest CT-scan involvement and hospitalization status. Results: CT findings showed lung involvement in 87 patients with chest CT-scan severity score (C-ss) of less than 8 in 59 (33%) and more than 8 in 28 (16%) of our patients. Of all patients, 76 (43%) were hospitalized. Hospitalized patients were significantly older and had more comorbidities (P = 0.02). On multivariate analysis, older age [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.31-3.08] and comorbidity (OR 2.75, 95% CI 1.06-3.66) were significantly associated with higher odds of hospitalization (P = 0.03). On multivariate analysis, older age (OR 1.15, 95% CI 0.94-2.01), pulmonary diseases (OR 2.05, 95% CI 1.18-3.32), and treatment with csDMARDs (OR 1.88, 95% CI 0.37-1.93) were associated with higher C-ss (P = 0.039). Conclusions: This study found that advanced age and comorbidities, similar to the general population, are risk factors for hospitalization in patients with COVID-19 with rheumatic disorders. Administration of csDMARDs, older age, and pulmonary disorders were linked to increased risk of COVID-19 pneumonia in these individuals.

Oral health-related quality of life in rheumatoid arthritis: a comparative analysis.

BACKGROUND: Compared to the healthy population, the psychological impact of rheumatoid arthritis(RA) on patients' lives could dramatically lower their oral health-related quality of life (OHRQoL). Our goal is to analyze OHRQoL in RA patients and look into the role of disease activity, dental health index, and Temporomandibular disorders score in maintaining their oral health. METHODS: In a cross-sectional comparative study, we compared a sample of 40 RA patients with 40 age- and gender-matched healthy controls in terms of oral health and OHRQoL. Temporomandibular disorders (TMD), number of decayed, filled, or missing teeth (DMFT), and Oral Health Impact Profile (OHIP) were among the oral health factors studied (OHIP-14). This study also looked at the link between the RA disease activity score (DAS28) and oral health factors. RESULTS: RA patients had a significantly higher mean (poorer OHRQol) than healthy controls in total oral function, total psychosocial impact, OHIP-14 sum score, OHIP-14 extent score, TMD score and the number of missed teeth (Mann-Whitney U test, P-value < 0.05). After adjustment for DMFT, only the oral function score of OHIP-14 had a significant correlation with disease activity (Mann-Whitney U test, P-value < 0.05). The TMD sum score significantly correlated with disease activity regardless of adjustment for DMFT (Spearman's Correlation test, P-value < 0.05 for both). The number of decayed teeth and missed teeth showed a positive correlation with increased disease activity (Coefficient = 0.239 and 0.245, P-value < 0.05 for both). CONCLUSIONS: Patients with RA are less satisfied with their oral health than healthy controls. In RA patients, the number of missing teeth and temporomandibular disorders was substantially greater, and the number of missing teeth and temporomandibular diseases increased significantly with increased disease activity. Although OHRQoL was inversely connected with RA activity, after correcting for decaying, missing, and filled teeth, only the oral function score of OHIP-14 exhibited a slight connection to DAS28.

Delirium risk factors in hospitalized patient: a comprehensive evaluation of underlying diseases and medications in different wards of a large Urban Hospital Center in Iran.

BACKGROUND: Delirium is a neurobehavioral syndrome, which is characterized by a fluctuation of mental status, disorientation, confusion and inappropriate behavior, and it is prevalent among hospitalized patients. Recognizing modifiable risk factors of delirium is the key point for improving our preventive strategies and restraining its devastating consequences. This study aimed to identify and investigate various factors predisposing hospitalized patients to develop delirium, focusing mostly on underlying diseases and medications. METHOD: In a prospective, observational trial, we investigated 220 patients who had been admitted to the internal, emergency, surgery and hematology-oncology departments. We employed the Confusion Assessment Method (CAM) questionnaire, The Richmond Agitation Sedation Scale (RASS), the General Practitioner Assessment of Cognition (GPCOG), demographic questionnaire, patient interviews and medical records. Multivariate logistic regression models were used to analyze the predictive value of medications and underlying diseases for daily transition to delirium.; demographics were analyzed using univariate analysis to identify those independently associated with delirium. RESULTS: Two hundred twenty patients were enrolled; the emergency department had the most incident delirium (31.3%), and the surgery section had the least (2.4%); delirium was significantly correlated with older ages and sleep disturbance. Among multiple underlying diseases and the medications evaluated in this study, we found that a history of dementia, neurological diseases and malignancies increases the odds of transition to delirium and the use of anticoagulants decreases the incident delirium. CONCLUSION: Approximately 1 out of 10 overall patients developed delirium; It is important to evaluate underlying diseases and medications more thoroughly in hospitalized patients to assess the risk of delirium.

Depression and anxiety increase the odds of developing delirium in ICU patients; a prospective observational study.

BACKGROUND: Delirium is prevalent among hospitalised patients, especially in critically ill patients. Preventing delirium by recognising its modifiable risk factors could improve life quality, decrease mortality and restrain its devastating consequences. METHOD: We investigated 50 patients who had been hospitalised in the general ICU and monitored them for developing delirium. We employed CAM and CAM-ICU Scales to assess delirium, RASS score to determine the consciousness level, HADS questionnaire for anxiety and depression, and the demographic data questionnaire. RESULTS: We found that 20% of ICU patients developed delirium and found a meaningful correlation between the incident delirium, older ages, visual impairment, and higher anxiety and depression scores (HADS) of first and second days of hospitalisation. By utilising logistic regression, we found that older ages, visual impairment, higher anxiety and depression scores (HADS) of the first day of hospitalisation were statistically significant to predict the risk model of developing delirium. CONCLUSION: Depressive and anxiety symptoms were associated with higher odds of transitioning to delirium; so, at the admission time, it may be useful to screen patients for the symptoms of affective disorders, particularly, who are at higher risks for developing delirium.

Medical Waste Management in Community Health Centers.

BACKGROUND: Non-standard management of medical waste leads to irreparable side effects. This issue is of double importance in health care centers in a city which are the most extensive system for providing Primary Health Care (PHC) across Iran cities. This study investigated the medical waste management standards observation in Tabriz community health care centers, northwestern Iran. METHODS: In this triangulated cross-sectional study (qualitative-quantitative), data collecting tool was a valid checklist of waste management process developed based on Iranian medical waste management standards. The data were collected in 2015 through process observation and interviews with the health center's staff. RESULTS: The average rate of waste management standards observance in Tabriz community health centers, Tabriz, Iran was 29.8%. This case was 22.8% in dimension of management and training, 27.3% in separating and collecting, 31.2% in transport and temporary storage, and 42.9% in sterilization and disposal. Lack of principal separation of wastes, inappropriate collecting and disposal cycle of waste and disregarding safety tips (fertilizer device performance monitoring, microbial cultures and so on) were among the observed defects in health care centers supported by quantitative data. CONCLUSION: Medical waste management was not in a desirable situation in Tabriz community health centers. The expansion of community health centers in different regions and non-observance of standards could predispose to incidence the risks resulted from medical wastes. So it is necessary to adopt appropriate policies to promote waste management situation.