Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID-19 infection.

Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. Dopamine receptors are widely distributed throughout the nervous system and in immune cells. Several viruses, including human immunodeficiency virus and Japanese encephalitis virus, can use dopaminergic receptors to replicate in the nervous system and are involved in viral neuropathogenesis. In addition, studies suggest that dopaminergic receptors may play a role in the progression and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds to angiotensin-converting enzyme 2 receptors on the surface of neuronal cells, the spike protein of the virus can bind to dopaminergic receptors on neighbouring cells to accelerate its life cycle and exacerbate neurological symptoms. In addition, recent research has shown that dopamine is an important regulator of the immune-neuroendocrine system. Most immune cells express dopamine receptors and other dopamine-related proteins, indicating the importance of dopaminergic immune regulation. The increase in dopamine concentration during SARS-CoV2 infection may reduce immunity (innate and adaptive) that promotes viral spread, which could lead to neuronal damage. In addition, dopaminergic signalling in the nervous system may be affected by SARS-CoV-2 infection. COVID -19 can cause various neurological symptoms as it interacts with the immune system. One possible treatment strategy for COVID -19 patients could be the use of dopamine antagonists. To fully understand how to protect the neurological system and immune cells from the virus, we need to study the pathophysiology of the dopamine system in SARS-CoV-2 infection.

Prediction of the Fatal Acute Complications of Myocardial Infarction via Machine Learning Algorithms.

Background: Myocardial infarction (MI) is a major cause of death, particularly during the first year. The avoidance of potentially fatal outcomes requires expeditious preventative steps. Machine learning (ML) is a subfield of artificial intelligence science that detects the underlying patterns of available big data for modeling them. This study aimed to establish an ML model with numerous features to predict the fatal complications of MI during the first 72 hours of hospital admission. Methods: We applied an MI complications database that contains the demographic and clinical records of patients during the 3 days of admission based on 2 output classes: dead due to the known complications of MI and alive. We utilized the recursive feature elimination (RFE) method to apply feature selection. Thus, after applying this method, we reduced the number of features to 50. The performance of 4 common ML classifier algorithms, namely logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost), was evaluated using 8 classification metrics (sensitivity, specificity, precision, false-positive rate, false-negative rate, accuracy, F1-score, and AUC). Results: In this study of 1699 patients with confirmed MI, 15.94% experienced fatal complications, and the rest remained alive. The XGBoost model achieved more desirable results based on the accuracy and F1-score metrics and distinguished patients with fatal complications from surviving ones (AUC=78.65%, sensitivity=94.35%, accuracy=91.47%, and F1-score=95.14%). Cardiogenic shock was the most significant feature influencing the prediction of the XGBoost algorithm. Conclusion: XGBoost algorithms can be a promising model for predicting fatal complications following MI.

Molecular signaling pathways, pathophysiological features in various organs, and treatment strategies in SARS-CoV2 infection.

Cytokine storms and extra-activated cytokine signaling pathways can lead to severe tissue damage and patient death. Activation of inflammatory signaling pathways during Cytokine storms are an important factor in the development of acute respiratory syndrome (SARS-CoV-2), which is the major health problem today, causing systemic and local inflammation. Cytokine storms attract many inflammatory cells that attack the lungs and other organs and cause tissue damage. Angiotensin-converting enzyme 2 (ACE2) are expressed in a different type of tissues. inhibition of ACE2 activity impairs renin-angiotensin (RAS) function, which is related to the severity of symptoms and mortality rate in COVID-19 patients. Different signaling cascades are activated, affecting various organs during SARS-CoV-2 infection. Nowadays, there is no specific treatment for COVID-19, but scientists have recognized and proposed several treatment alternatives, including applying cytokine inhibitors, immunomodulators, and plasma therapy. Herein, we have provided the detailed mechanism of SARS-CoV-2 induced cytokine signaling and its connection with pathophysiological features in different organs. Possible treatment options to cope with the severe clinical manifestations of COVID-19 are also discussed.

The importance of neopterin in COVID-19: The prognostic value and relation with the disease severity.

Coronavirus Disease 2019 [COVID-19], caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], has rapidly evolved into a global health emergency. Neopterin [NPT], produced by macrophages when stimulated with interferon [IFN-]gamma, is an essential cytokine in the antiviral immune response. NPT has been used as a marker for the early assessment of disease severity in different diseases. The leading cause of NPT production is the pro-inflammatory cytokine IFN-. Macrophage activation has also been revealed to be linked with disease severity in SARS-CoV-2 patients. We demonstrate the importance of NPT in the pathogenesis of SARS-CoV-2 and suggest that targeting NPT in SARS-CoV-2 infection may be critical in the early prediction of disease progression and provision of timely management of infected individuals.

Glycemic control in the infectious diseases ward; role of clinical pharmacist interventions.

INTRODUCTION: Hyperglycemia is one of the most frequent metabolic complications in hospitalized patients. Increased risk of infection following hyperglycemia has been reported in hospitalized patients and infections may also cause insulin resistance which complicates the control of blood glucose level. In this study the impact of the clinical pharmacist interventions on the glycemic control in patients admitted to infectious diseases ward has been evaluated. METHODOLOGY: We conducted a prospective, pre-post interventional study among patients with hyperglycemia. The clinical pharmacist-led multidisciplinary team managed the glycemic profile of patients according to an established insulin protocol commonly used in internal wards. Clinical pharmacists reviewed patients' medical charts for proper insulin administration, evaluated nurses' technique for insulin injection and blood glucose measurement, and educated patients about symptoms of hypoglycemia and the importance of adherence to different aspects of their glycemic management. RESULTS: The percentage of controlled random blood sugar increased from 13.8% in the pre-intervention to 22.3% in the post-intervention group (p value < 0.01). On the other hand, the percentage of controlled fasting blood sugars in the post-intervention group was non-significantly higher than in the pre-intervention group. CONCLUSION: Pharmacists and additional health care providers from other departments such as nursing and dietary departments need to be devoted to glycemic control service. Collaborative practice agreement between physicians is necessary to promote this service and help to increase the use of such services in different settings for diabetes control.

Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: a randomized, clinical trial.

BACKGROUND AND AIM: In the present study, the potential benefits of oral carnitine in preventing antituberculosis drug-induced hepatotoxicity (ATDH) were evaluated. METHODS: Fifty-four patients in the carnitine and 62 patients in the placebo group completed the study. The carnitine group received 1000 mg oral carnitine solution twice daily for 4 weeks. The placebo group received 10 mL of oral placebo solution twice daily for 4 weeks. ATDH was defined as an increase in the serum level of aspartate aminotransferase or alanine aminotransferase greater than three or five times of the upper limit of normal with or without clinical symptoms of hepatotoxicity, respectively. RESULTS: During the study period, 29 (25%) patients experienced ATDH. Among these patients, nine (16.7%) and 20 (32.3%) were in the carnitine and placebo groups, respectively (P = 0.049). Based on multivariate logistic regression model, age over 35 years old (odds ratio [OR] = 7.01, P = 0.002), human immunodeficiency virus infection (OR = 40.4, P < 0.001), diabetes mellitus (OR = 37.6, P = 0.001), and placebo treatment (OR = 0.1, P = 0.01) were identified as predisposing factors for ATDH. CONCLUSION: Results of our preliminary clinical trial suggested that cotreatment with 2000 mg oral L-carnitine solution daily for 4 weeks significantly decreased the rate of ATDH.

Carnitine and sepsis: a review of an old clinical dilemma.

PURPOSE: The precise role of carnitine as the key regulator of lipid metabolism in sepsis is unclear. In this review, available experimental as well as clinical evidences regarding the probable beneficial effects of carnitine in sepsis were evaluated. METHOD: A comprehensive literature search was performed in the related medical databases. Related experimental and clinical studies were included. RESULTS AND CONCLUSION: The plasma and tissue level of carnitine or its derivatives in septic condition is variable and inconclusive. Survival and outcomes are considered in only few studies. Despite its favorable safety profile, due to limited clinical evidence, it seems reasonable not to currently consider carnitine as a mandatory and beneficial supplement under septic conditions. Further well-designed, standard clinical trials are warranted in this regards.

Carnitine deficiency and its possible risk factors in TB patients: first report.

AIM: To assess carnitine serum levels and possible risk factors of its deficiency in patients with TB. PATIENTS & METHODS: All newly diagnosed TB patients admitted to an infectious diseases ward were recruited. Demographic, clinical and paraclinical characteristics of the patients were collected. Total carnitine serum concentrations were measured. To investigate factors that can predict carnitine deficiency, logistic regression analysis with odds ratio and 95% CI was performed. RESULTS: The mean ± standard deviation of carnitine serum levels of patients was 43.77 ± 32.92 µmol/l. Carnitine deficiency was detected in 47.7% of the study population. According to the final model of multivariate logistic regression analysis, increased serum triglyceride levels and hypoalbuminemia were identified as predictive factors of carnitine deficiency in TB patients aged over 35 years old. CONCLUSION: Nearly half of Iranian patients with TB were carnitine-deficient. Increased serum triglyceride levels and hypoalbuminemia were identified as independent risk factors of carnitine deficiency in patients aged over 35 years. Considering malnutrition as a major risk factor of TB and the safety of carnitine supplementation, use of carnitine as an adjunctive modality instead of other standard interventions may show beneficial effects in patients with TB.

Frequency of depression and its correlation with serum carnitine level in HIV/AIDS patients.

There are some evidences regarding beneficial effects of carnitine in improvement of depression symptoms. Incidence of depression is significantly higher among HIV positive individuals compared to HIV negative populations. Also carnitine deficiency is prevalent in HIV positive individuals. In a cross-sectional study correlation between serum carnitine level and depression severity based on the Beck Depression Inventory questionnaire was assessed in 100 HIV/AIDS (42 males and 58 females) patients. According to the Beck Depression Inventory definitions, 31%, 16%, and 21% of the patients experienced mild, moderate, and severe depression, respectively. The mean ± SD serum concentration of total carnitine in the patients was 37.96 ± 26.08 (µmol/L). Fifty-four (54%) patients were categorized as carnitine deficient. A non-statistically significant negative correlation between patients' depression scores and total levels of serum carnitine was found. Considering the prevalence of depression among HIV/AIDS patients and probable role of carnitine in the pathogenesis of depressive disorders, more studies are needed to reveal correlation between depression and the body storage of carnitine.

Prevention of vancomycin induced nephrotoxicity: a review of preclinical data.

PURPOSE: Several strategies have been proposed for the prevention of vancomycin-induced nephrotoxicity. Here, we review available evidence supporting the respective strategies. METHOD: Data were collected by searching the Scopus, PubMed, and Medline databases and the Cochrane database of systematic reviews. The key words used as search terms were "vancomycin," "nephrotoxicity", "renal failure," "renal damage," "nephroprotective," "renoprotective", and "prevention." Prospective or retrospective observational animal studies that evaluated the effects of a modality for the prevention of vancomycin-induced nephrotoxicity was included. RESULTS AND CONCLUSION: Animal studies show beneficial effects of various antioxidants, such as erdosteine, vitamin E, vitamin C, N-acetylcysteine, caffeic acid phenethyl ester, and erythropoietin, in the prevention of vancomycin-induced nephrotoxicity. However, before these agents can be used in clinical practice, their potential benefits must be confirmed in future randomized controlled human studies.

Intraocular pressure after exposure to moderate altitude.

BACKGROUND: To study intraocular pressure (IOP) alteration in healthy individuals following a rapid effortless increase in altitude from 1900 m above sea level (ASL) to 3740 m ASL. METHODS: Intraocular pressure, blood pressure, pulse rate, and arterial oxygen tension were determined in both eyes of healthy volunteers at the lower altitude. Participants were taken to a higher altitude of 3740 m ASL (1840-m altitude gain) via gondola lift, which took 30 minutes. All measurements were repeated at the higher altitude. Pearson and Spearman correlation analysis was conducted to assess the correlations among the variables. A paired t-test and linear regression were also used to compare IOP before and after ascending. The accepted level of significance for all tests was p <0.05. RESULTS: Fifty-four healthy volunteers participated in the study. Four eyes of three subjects with IOP higher than 21 mmHg were excluded. Intraocular pressure ± SD (range) decreased from 14.9 ± 2.6 mmHg (9-21 mmHg) to 14.3 ± 2.4 mmHg (11-20 mmHg) (p = 0.02) after the ascent. Arterial oxygen saturation decreased from 95.4 % to 91.5 % (p < 0.001). Neither of the participants complained of any ocular or systemic symptoms during or after ascending to the higher altitude. Mean IOP, before and after ascending, was positively correlated with systolic blood pressure before and after the increase in altitude (Pearson correlation coefficient, 0.41, p = 0.002 and Pearson correlation coefficient, 0.37, p = 0.006, respectively). Intraocular pressure changes did not correlate with age, pulse rate, or arterial oxygen saturation. CONCLUSION: A rapid, effortless increase in altitude (over a moderate range in altitude) decreases IOP in healthy individuals. The observed decrease may not be clinically significant; however, it shows the versatility of IOP control mechanisms in response to alteration in altitude and temperature.

Adherence to empiric antibiotic therapy guideline in a referral teaching hospital, Tehran, Iran.

Antibiotic guidelines have proven to be a simple and effective intervention to guide the choice of appropriate empiric antibiotic regimens. The goals of this study were to evaluate adherence to guidelines and streamlining of antibiotics. Hospital records of hospitalized patients in infectious diseases ward Imam Khomeini Hospital, Tehran, Iran, from May 2008 to September 2009 were reviewed. Adherence to guideline was defined as the use of empiric antibiotic in accordance with the clinical diagnosis and local guideline recommendations. In this study, 528 patients with a confirmed infectious disease diagnosis were considered for analysis. The four most frequent diagnoses were skin and soft tissue infections, tuberculosis, respiratory tract infections, and HIV associated opportunistic infections. The most frequent prescribed antibiotic was ceftriaxone. Overall adherence to guideline was 70.8% and the adherence for the most frequent diagnosis was 68%. Frequency of compatibility with the guidelines for were administrated regimes on the basis of drug selection, dosage form and drug dosing were 86.2%, 97% and 84.7%, respectively. The mean lag time between patients' hospital admission and starting empiric therapy was 1.69 ± 4.9 days. In general, physicians' adherence with guidelines for empiric antibiotic therapy was high in infectious disease ward with a justified delay. Larger studies are required to establish these conclusions.