Epidural and subdural hematoma following spinal anesthesia in infants rat model.

The aim of this study was to assess the epidural and subdural hematoma following spinal anesthesia in infants' rat model. We investigated during 10, 15, and 20 days' rats in group 1: intrathecal injection of bupivacaine 3.75 mg/kg (n = 7); group 2: received 37.5 µl midazolam 0.1% intrathecal with 37.5µl fentanyl 0.005% (no=7); injected into group 3 methylene blue 1 mg/ml (No. 7). Rats were exposed to spinal anesthesia in infancy and rotarod in motor function in adulthood. Histological evaluation and tissue extraction were also performed after the treatment and magnetic resonance imaging (MRI) of the head. MRI of the head of all rat pups that showed similar symptoms were performed. 4 rat pups showed the symptoms of hematoma Group1: small acute subdural hematoma at the left posterior temporal-parietal junction (PTPJ) and group 2 (one: right temporal epidural hematoma, two: Small acute subdural hematoma in the right temporomandibular area, and three: frontal-temporal-parietal-occipital hematoma). the rat pup that had epidural hematoma died 6 hours later. Finally, in the first group, one rat and the second group three rats showed hematoma symptoms. For these three rats, a histopathologic study was performed and indicate the presence of small acute subdural hematoma at the left posterior temporal-parietal junction, right temporal epidural hematoma, and frontal-temporal-parietal-occipital hematoma. In summary, because subdural or epidural hematoma of the skull can have serious consequences, differential diagnosis is very important for pain after spinal anesthesia.

COVID-19 management in Iran and international sanctions.

Iran has one of the highest death rates from COVID-19 among Middle Eastern countries. In addition to having a better disease registration system compared to neighboring countries, many factors including economic conditions, have played an important role in increasing the number of mortality rate. This is while that during the Corona pandemic, Iran has been undergo severe sanctions by the United States, that has faced this country with a severe economic crisis. Considering the role of sanction on the country's health management in our study, we examined Iran's management plans against the Corona pandemic and the effect of sanctions on it. Quarantine and corona restrictions, on the one hand, and international sanctions, on the other hand, have put double pressure on the Iranian government. Although drugs and basic medical equipment are exempted from economic sanctions, direct and indirect effects of the sanctions have limited Iran's banking system and created widespread restrictions in the fields of trade, production, and investment. Fortunately, despite the sanctions, many hospitals had an appropriate performance in line with the health promotion program. It is obvious that economic sanctions have severe and harmful effects on public health and have led to poor health consequences in Iran, but attention to planning, standards and improving the quality of the hospital is an important issue in Corona management. Despite multiple mutations, this virus is likely to face with a more dangerous virus in the world future. Now, it is time to take appropriate management measures to remove these sanctions by relying on international solutions and interactions.

Cellular and Molecular Aspects of Managing Familial Hypercholesterolemia: Recent and Emerging Therapeutic Approaches.

Familial hypercholesterolemia (FH) as a high-frequency genetic disorder is diagnosed based on family and/or patient's history of coronary heart disease (CHD) or some other atherosclerotic diseases, LDL-C levels, and/or clinical signs such as tendinous xanthoma, arcus cornealis before age 45 years as well as a functional mutation in the LDLR, apoB or PCSK9 gene. Its clinical features are detectable since early childhood. Early diagnosis and timely treatment increase life expectancy in most patients with FH. Current FH therapies decrease the level of lowdensity lipoprotein up to ≥50% from baseline with diet, pharmacotherapeutic treatment, lipid apheresis, and liver transplantation. The cornerstone of medical therapy is the use of more potent statins in higher doses, to which often ezetimibe has to be added, but some FH patients do not achieve the target LDL-C with this therapy Therefore, besides these and the most recent but already established therapeutic approaches including PCSK9 inhibitors, inclisiran, and bempedoic acid, new therapies are on the horizon such as gene therapy, CRISPR/Cas9 strategy, etc. This paper focuses on cellular and molecular potential strategies for the treatment of FH.

Insights on my future job: implementing near-peer shadowing program for operating room freshmen.

BACKGROUND: As a main challenge in paramedical faculties of medical sciences, freshmen lose interest in their academic field of study and then job motivation. Lack of developed knowledge about their academic field and unfamiliarity with their future job's tasks and roles contribute to freshmen's job motivation loss. Various interventional programs have been implemented to improve students' job motivation by familiarizing them with their future job's duties and responsibilities. METHODS: This was one-group pretest-posttest design study in 2019-2020. Students grouped into pairs of a freshman (shadowee) with a senior (shadower) in a clinical setting during shadowing program. This program helps freshmen to comprehend and discover realities of their academic field and can help them change their perspectives regarding their future job's duties and responsibilities. The shadowees' main task was reflective observation on operating room events and interactions and to be active in the program, several tasks e.g., how to wear gloves, guns, and disinfect equipment were assigned to them exclusively under the supervision of senior students. The Hackman and Oldham's Job Diagnostic Survey (JDS) questionnaire and a novel Job Motivation Survey (JMS) questionnaire were distributed among participants. RESULTS: Fifty freshmen majoring in operating room participated in the shadowing program from November 2019 to January 2020. Before and after the program, they completed Hackman and Oldham's job diagnostic survey and researcher-made job motivation survey questionnaires. Results were indicative of a significant difference in job diagnostic survey questionnaire score, where overall pre-test and post-test scores before and after the intervention were 57.78 (±9.78) and 68.58 (±5.02), respectively; the score difference was statistically significant (P < 0.001). Moreover, the overall pre-test and post-test scores of the job motivation survey questionnaire were 25.16 (± 9.75) and 39.80 (±5.18), respectively; this score difference was statistically significant (P < 0.001). CONCLUSION: Shadowing program improved freshmen's realistic perception of their future job's duties and responsibility, and hence enhancing their job motivation and job recognition. As future work, in various disciplines, further studies need to evaluate the impact of such interventional programs in providing early insights for freshmen as well as in providing guidance on their plans for education, and future job.

Epigenetic aspects of multiple sclerosis and future therapeutic options.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease accompanied by demyelination of neurons in the central nervous system that mostly affects young adults, especially women. This disease has two phases including relapsing-remitting form (RR-MS) by episodes of relapse and periods of clinical remission and secondary-progressive form (SP-MS), which causes more disability. The inheritance pattern of MS is not exactly identified and there is an agreement that it has a complex pattern with an interplay among environmental, genetic and epigenetic alternations. Epigenetic mechanisms that are identified for MS pathogenesis are DNA methylation, histone modification and some microRNAs' alternations. Several cellular processes including apoptosis, differentiation and evolution can be modified along with epigenetic changes. Some alternations are associated with epigenetic mechanisms in MS patients and these changes can become key points for MS therapy. Therefore, the aim of this review was to discuss epigenetic mechanisms that are associated with MS pathogenesis and future therapeutic approaches.

Molecular and cellular mechanisms of the effects of Propolis in inflammation, oxidative stress and glycemic control in chronic diseases.

Propolis is a sticky, resinous material gather from plants and is blended with wax and other constituents. It is reported to have anti-inflammatory, anti-oxidative and blood glucose-lowering properties. This review aims to summarise evidences for the cellular and molecular mechanism of Propolis in inflammation, oxidative stress, and glycemic control. Propolis stimulate the production and secretion of anti-inflammatory cytokines and to inhibit the production of inflammatory cytokines and due to its various antioxidant and poly-phenolic compounds may has a role in control and treating some of the chronic diseases. Most studies have shown that Propolis may affect metabolic factors including plasma insulin levels, and it has proposed that it could be used in the prevention and treatment of T2D Mellitus. In general, to demonstrate the definite effects of Propolis on chronic diseases, more studies are required using larger sample sizes and various doses of Propolis, using better characterized and standardized agents.

A novel variant in C5ORF42 gene is associated with Joubert syndrome.

Joubert syndrome (JS) disease is a clinically and genetically heterogeneous disorder with mutations in more than 35 genes involved in its pathogenicity. Molecular genetic methods including next generation sequencing (NGS) and Sanger sequencing are effective techniques used for identifying rare genetic variants that have a strong effect on disease pathogenesis. In this study, we tested a large pedigree with a history of several affected members with JS. At first the proband was sequenced by NGS technique then, confirmed by sanger sequencing method. After this, all available members of the pedigree were subjected to molecular analysis by sanger sequencing technique. The results of this study showed a novel variant in the C5ORF42 gene c.3080A > T: p. D1027V leading to a substitution of a valine for aspartic acid (D1027V) and may be associated with JS. This variant was present in proband compatible with autosomal recessive pattern. Also this variant was present in all parents (both father and mother) of affected individuals in a heterozygous state. It seems that mutations in C5ORF42 gene are associated with JS. However, the substantial mechanism requires further investigation.

Limb-girdle Muscular Dystrophy and Therapy: Insights into Cell and Gene-based Approaches.

The Limb-Girdle Muscular Dystrophies (LGMD) are genetically heterogeneous disorders, responsible for muscle wasting and severe form of dystrophies. Despite the critical developments in the insight and information of pathomechanisms of limb-girdle muscular dystrophy, any definitive treatments do not exist, and current strategies are only based on the improvement of the signs of disorder and to enhance the life quality without resolving an underlying cause. There is a crucial relationship between pharmacological therapy and different consequences; therefore, other treatment strategies will be required. New approaches, such as gene replacement, gene transfer, exon skipping, siRNA knockdown, and anti-myostatin therapy, which can target specific cellular or molecular mechanism of LGMD, could be a promising avenue for the treatment. Recently, genome engineering strategies with a focus on molecular tools such as CRISPR-Cas9 are used to different types of neuromuscular disorders and show the highest potential for clinical translation of these therapies. Thus, recent advancements and challenges in the field will be reviewed in this paper.

The atherogenic role of immune cells in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism that mainly occurs due to mutations in the low-density lipoprotein receptor gene and is characterized by increased levels of low-density lipoprotein cholesterol, leading to accelerated atherogenesis and premature coronary heart disease. Both innate and adaptive immune responses, which mainly include monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes, have been shown to play a key role for the initiation and progression of atherogenesis in the general population. In FH patients, these immune cells have been suggested to play specific pro-atherosclerotic activities, from the initial leukocyte recruitment to plaque rupture. In fact, the accumulation of cholesterol crystals and oxLDL in the vessels in FH patients is particularly high, with consequent abnormal mobilization of immune cells and secretion of various pro-inflammatory and chemokines. In addition, cholesterol accumulation in immune cells is exaggerated with chronic exposure to relevant pro-atherosclerotic triggers. The topics considered in this review may provide a more specific focus on the immune system alterations in FH and open new insights toward immune cells as potential therapeutic targets in FH.

Familial combined hyperlipidemia: An overview of the underlying molecular mechanisms and therapeutic strategies.

Among different types of dyslipidemia, familial combined hyperlipidemia (FCHL) is the most common genetic disorder, which is characterized by at least two different forms of lipid abnormalities: hypercholesterolemia and hypertriglyceridemia. FCHL is an important cause of cardiovascular diseases. FCHL is a heterogeneous condition linked with some metabolic defects that are closely associated with FCHL. These metabolic features include dysfunctional adipose tissue, delayed clearance of triglyceride-rich lipoproteins, overproduction of very low-density lipoprotein and hepatic lipids, and defect in the clearance of low-density lipoprotein particles. There are also some genes associated with FCHL such as those affecting the metabolism and clearance of plasma lipoprotein particles. Due to the high prevalence of FCHL especially in cardiovascular patients, targeted treatment is ideal but this necessitates identification of the genetic background of patients. This review describes the metabolic pathways and associated genes that are implicated in FCHL pathogenesis. We also review existing and novel treatment options for FCHL. © 2019 IUBMB Life, 71(9):1221-1229, 2019.

Roles of E6 and E7 Human Papillomavirus Proteins in Molecular Pathogenesis of Cervical Cancer.

Human papillomavirus (HPV) cancers are expected to be major global health concerns in the upcoming decades. The growth of HPV-positive cancer cells depends on the consistent expression of oncoprotein which has been poorly taken into account in the cellular communication. Among them, E6/E7 oncoproteins are attractive therapeutic targets as their inhibition rapidly leads to the onset of aging in HPV-positive cancer cells. This cellular response is associated with the regeneration of p53, pRb anti-proliferative proteins as well as the mTOR signaling pathway; hence, the identification of involved and application of E6/E7 inhibitors can lead to new therapeutic strategies. In the present review, we focused on the pathogenicity of E6/E7 Proteins of human papillomavirus and their roles associated with the cervical cancer.

Involvement of aberrant regulation of epigenetic mechanisms in the pathogenesis of Parkinson's disease and epigenetic-based therapies.

Parkinson's disease (PD) is known as a progressive neurodegenerative disorder associated with the reduction of dopamine-secreting neurons and the formation of Lewy bodies in the substantia nigra and basal ganglia routes. Aging, as well as environmental and genetic factors, are considered as disease risk factors that can make PD as a complex one. Epigenetics means studying heritable changes in gene expression or function, without altering the underlying DNA sequence. Multiple studies have shown the association of epigenetic variations with onset or progression of various types of diseases. DNA methylation, posttranslational modifications of histones and presence of microRNA (miRNA) are among epigenetic processes involved in regulating pathways related to the development of PD. Unlike genetic mutations, most epigenetic variations may be reversible or preventable. Therefore, the return of aberrant epigenetic events in different cells is a growing therapeutic approach to treatment or prevention. Currently, there are several methods for treating PD patients, the most important of which are drug therapies. However, detection of genes and epigenetic mechanisms involved in the disease can develop appropriate diagnosis and treatment of the disease before the onset of disabilities and resulting complications. The main purpose of this study was to review the most important epigenetic molecular mechanisms, epigenetic variations in PD, and epigenetic-based therapies.

Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives.

Parkinson's disease is a neurodegenerative disorder accompanied by depletion of dopamine and loss of dopaminergic neurons in the brain that is believed to be responsible for the motor and non-motor symptoms in this disease. The main drug prescribed for Parkinsonian patients is L-dopa, which can be converted to dopamine by passing through the blood-brain barrier. Although L-dopa is able to improve motor function and improve the quality of life in the patients, there is inter-individual variability and some patients do not achieve the therapeutic effect. Variations in treatment response and side effects of current drugs have convinced scientists to think of treating Parkinson's disease at the cellular and molecular level. Molecular and cellular therapy for Parkinson's disease include (i) cell transplantation therapy with human embryonic stem (ES) cells, human induced pluripotent stem (iPS) cells and human fetal mesencephalic tissue, (ii) immunological and inflammatory therapy which is done using antibodies, and (iii) gene therapy with AADC-TH-GCH gene therapy, viral vector-mediated gene delivery, RNA interference-based therapy, CRISPR-Cas9 gene editing system, and alternative methods such as optogenetics and chemogenetics. Although these methods currently have a series of challenges, they seem to be promising techniques for Parkinson's treatment in future. In this study, these prospective therapeutic approaches are reviewed.

Molecular mechanisms, prevalence, and molecular methods for familial combined hyperlipidemia disease: A review.

Familial combined hyperlipidemia (FCHL) is the most common genetic dyslipidemia disorder which is accompanied by increasing of triglyceride and cholesterol. This disorder is a complex genetic disease although it also has monogenic forms. The familial form has several criteria for diagnosis that can be distinguished of nonfamilial position. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of FCHL. Environmental factors and the genetic background also play an important role in the FCHL pathogenesis. Many mechanisms and pathways are involved in lipid metabolism (ie, dysfunctional adipose tissue, hepatic fat and very low-density lipoprotein overproduction, triglyceride-rich lipoproteins, and clearance of low-density lipoprotein particles) that could lead to FCHL. Individuals with a positive family history like those who have a positive family history of cardiovascular diseases are more predispositions for this disorder. To date several methods have been used to identify the genetic background of the FCHL. In the current review, we summarized the prevalence and the molecular mechanisms involved in the FCHL disease. Moreover, we highlighted the used molecular methods for determining the genes involved in the FCHL.

Diabetes Mellitus in Thalassaemia Major Patients: A Report from the Southeast of Iran.

INTRODUCTION: Diabetes Mellitus (DM) represents a major concern in Thalassaemia Major (TM) patients. AIM: The present study was conducted to evaluate the frequency of Impaired Fasting Glucose (IFG) and DM in TM patients in Southeast of Iran. MATERIALS AND METHODS: Fasting Blood Glucose (FBS) was determined using fasting blood samples in 148 TM patients. Demographical data was collected by a questionnaire. Clinical and laboratory variables including cell blood counts, pre-transfusion Haemoglobin (Hb) level, and five-year ferritin were extracted from medical records. Statistical analysis was performed in SPSS19.0 software using chi-square, student t-test and logistic regression. RESULTS: Females and males comprised 83 (56.1%) and 65 (43.9%) subjects respectively. The mean age and mean five-year ferritin were 17.3±6.1 year-old and 5060.6±2395 ng/ml respectively. Overall, 39 (26.4%) patients had IFG, while 13 (8.8%) were diagnosed with DM. Significant differences were identified in the mean age, volume of transfused blood per occasion, and mean five-years ferritin between the patients with IFG or DM and the patients with normal fasting glucose level. Patients with age >25-year-old had an increased risk of both IFG (OR=4.7,95% CI: 1.3-17, p=0.01) and DM (OR= 7.1, 95% CI: 1-49.2, p=0.04). In addition, splenectomized patients showed a higher risk for IFG (OR=4.3, 95% CI: 1.5-12.1, p=0.005), and ferritin value >6000 ng/ml were associated with an elevated risk of DM (OR=7, 95% CI: 0.8-60.1, p=0.07). CONCLUSION: Our results indicated that higher age, mean five-years ferritin, volume of blood transfused per occasion, as well as splenectomy were risk factors of IFG and DM in TM patients.