Impact of Opium Addiction on Levels of Pro- and Anti-inflammatory Cytokines after ‎Surgery

Background: Opium addiction alters immune responses to stresses such as an injury due to changing the secretion of cytokines. The present study assessed the effect of opium addiction on the cytokines [tumor necrosis factor α (TNFα), interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10] before and after laparotomy. Methods: Male rats were randomly divided into control and opium addicted (n = 20). Then, cytokines were measured before surgery, immediately after surgery (within 30-60 minutes) and 24 hours after surgery. Findings: IFN-γ was raised in an addicted group in three phases of the study as compared to that of the control group. IL-4 in opium addicted group decreased in two phases after surgery compared to the control group. IL-4 was lower after surgery in comparison to before surgery in the opium addicted group. The difference in IL-10 and TNFα levels was not statistically significant in the all groups measured in three phases of the investigation. Conclusion: The results revealed that opium addiction can increase plasma level of IFN-γ in rats and decrease plasma level of IL-4 after surgical stress. It seems that opium addicted rats are a more susceptible to increased inflammation

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\u27 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\u27s 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

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Analysis of the leadership of Imam Khomaini during imposed war from the perspective of sociology of emotions

Reviewing Imam Khomeini’s leadership during the imposed war, this article in the incipient context of emotions sociology aimed to respond the question that how Imam orchestrated the feelings of the masses and the armed forces to strengthen their defensive spirit during the war. Applying a content qualitative analysis methodology on Imam’s writings and words, the paper argues that the based on elements such as divine-based fledgling society, God’s invisible hand, positive fear-provoking, considering war as blessing, promise of a victory, seeking similarity with Ashura and early Islam period to release and consolidate the emotional energies into a sense of responsibility, obtaining fame and honor, obtaining spiritual strength, self-sacrifice, commitment and collective solidarity, taking revenge, and showing anger to the enemy, Imam led the masses toward resistance against the Baathist regime and eventually brought them victory

The structure of International system and Turkish politics against ISIS

The purpose of this paper is to examine the change in Turkish strategy against ISIS from "support" to "battling". In order to understand is used the approach of the "structure of the international system," which is a synthesis of "regional hegemonic structure" and "trans-regional repulse structure" to indicate why Turkey is carried out to the "big change". For this purpose, is used descriptive-analytical method and relied on documentary sources through library research. The findings show because of the limitations of the regional structure due to superiority of Kurds, the axis of resistance and Russia as the dominant forces on the one hand and Trans-regional systemic pressures due to discredit front of the US, EU and international institutions / world public opinion, on the other hand, turkey was forced to strategic turn in its policy against ISIS. So, this kind of revisionism comes from a tradition based on realistic in order to restore power and national security not from the revolutionary tradition based on real determination to fight terrorism

A Comprehensive Review on Electrochemical Nano Biosensors for Precise Detection of Blood-Based Oncomarkers in Breast Cancer

Breast cancer (BC), one of the most common and life-threatening cancers, has the highest incidence rate among women. Early diagnosis of BC oncomarkers is considered the most effective strategy for detecting and treating BC. Finding the type and stage of BC in women as soon as possible is one of the greatest ways to stop its incidence and negative effects on medical treatment. The development of biosensors for early, sensitive, and selective detection of oncomarkers has recently attracted much attention. An electrochemical nano biosensor (EN) is a very suitable option for a powerful tool for cancer diagnosis. This comprehensive review provides information about the prevalence and pathobiology of BC, recent advances in clinically available BC oncomarkers, and the most common electrochemical nano biosensors for point-of-care (POC) detection of various BC oncomarkers using nanomaterial-based signal amplification techniques

Menstrual Irregularities and Related Plasma Hormone Levels in Multiple Sclerosis Patients Treated with Beta Interferone

Multiple sclerosis is a chronic inflammatory disease of central nervous system.Women are more susceptible to this disease. One of the obvious clinical complaints in women with multiple sclerosis specially treated with Beta Interferones is menstrual cycle irregularity. The aim of this study was to determine the prevalence of menstrual irregularities and probable changes in blood levels of related hormones (FSH, LH, PRL, TSH, T4, T3) in 58 females with definite MS treated with beta interferones versus 58 healthy women. In comparison to the control group, the patients had higher prevalence of irregular menstruation (P=0.001), oligomenorrhea (p=0.03), abnormal amount of menstrual blood flow (P=0.001), abnormal duration of menstrual flow (P=0.01) and missed period (P=0.04). Mean LH level in patients group was higher than control group (P=0.04).Hyperprolactinemia (>25.5ng/ml) was more prevalent in patients group .There were not a significant difference in plasma levels of FSH and thyroid hormones between two groups. There were some relations between the type of Beta interferones and the subtype of menstrual irregularities in the patients. In conclusion, the results of this study emphasized the high rate of menstrual problem and changes of related plasma hormone levels in MS patients

Effect of Silymarin on Hepatic Complications Caused by Methotrexate and its Analgesic Effects in Patients with Rheumatoid Arthritis

Background and Aim: Methotrexate is an important drug for treatment of rheumatoid arthritis (RA) but is associated with adverse side effects on liver. In this study we evaluated the effect of silymarin on methotrexate induced hepatotoxicity and its analgesic effects in the patients taking this drug. Materials and Methods: This study inclouded 58 patients with RA. Patients who had been treated with 2.5 mg methotrexate three times a week for six months were randomly divided into two groups of A and B. Group A received methotrexate and group B treated with 280 mg of silymarin tablets daily (two doses for 2 months) in addition to methotrexate. At baseline (before tests) and after two months, both groups completed the VAS (Visual Analogue Scale) questionnaire and Cr (Creatinine), BUN (Blood Urea Nitrogen), ESR (Erythrocyte Sedimentation Rate), Hemoglobin, WBC (white blood cell), PLT (Platelet) and the liver tests including ALT (Alanine Transaminase) and AST (Aspartate Aminotransferase) were evaluated. We used t-test for data analysis. Results: In the group B, ALT, AST and ESR, Cr and BUN decreased significantly. Also clinical signs of pain which were indicative of pain intensity were decreased. Conclusion: Use of silymarin in the patients with RA reduced liver enzymes, liver toxicity and renal complications, which may be due to its antioxidant and cell membrane stabilization properties

Novel homozygous frameshift variant in the ATCAY gene in an Iranian patient with Cayman cerebellar ataxia; expanding the neuroimaging and clinical features: a case report

Abstract Background Pathogenic variants in the ATCAY gene are associated with a rare autosomal recessive disorder called Cayman cerebellar ataxia. Affected individuals display psychomotor retardation, cerebellar dysfunction, nystagmus, intention tremor, ataxic gait and dysarthric in some cases. Case presentation Whole exome sequencing was performed for a 21-month-old girl suffering from developmental delay specifically in motor and language aspects, hypotonia, nystagmus, pes planus and strabismus. The detected variant in the patient was confirmed by family segregation analysis by Sanger sequencing in both of her parents. Previously three homozygous variants in the ATCAY gene (missense, splice site and frameshift deletion) have been reported in patients with Cayman cerebellar ataxia. Here we report the fourth homozygous variant and the second homozygous frameshift deletion in this gene to be associated with autosomal recessive Cayman cerebellar ataxia. Conclusion The identification of this novel homozygous frameshift deletion in the ATCAY gene expands our understanding of the genetic landscape underlying Cayman cerebellar ataxia. Furthermore, the occurrence of this variant in Iran, in addition to Pakistan, signifies the importance of considering genotypic and phenotypic factors beyond ethnicity when studying this disorder. These findings contribute to the ongoing efforts to unravel the molecular basis of Cayman cerebellar ataxia and improve diagnostic approaches and potential therapeutic interventions

Resistance mechanisms to immune checkpoints blockade by monoclonal antibody drugs in cancer immunotherapy: Focus on myeloma

Baradaran, Behzad/0000-0002-8642-6795; Hajiasgharzadeh, Khalil/0000-0003-4593-4803; baghbanzadeh, amir/0000-0002-1261-3213WOS: 000543385400001PubMed: 32592235Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of neoplastic proliferation of a plasma cell in the bone marrow that produces a monoclonal immunoglobulin. the immune checkpoint inhibitors against programmed death-1/programmed death-1 ligand and cytotoxic T-lymphocyte antigen 4 axis have demonstrated appropriate anticancer activity in several solid tumors and liquid cancers, and are rapidly transforming the practice of medical oncology. However, in a high percentage of patients, the efficacy of immune checkpoints blockade remains limited due to innate or primary resistance. Moreover, the malignancies progress in many patients due to acquired or secondary resistance, even after the clinical response to immune checkpoints' blockade. the evidence shows that multiple tumor-intrinsic and tumor-extrinsic factors and alterations in signaling pathways are involved in primary and secondary resistance to immune checkpoints blockade. Improved identification of intrinsic and extrinsic factors and mechanisms of resistance or response to immune checkpoints blockade may not only provide novel prognostic or predictive biomarkers but also guide the optimal combination/sequencing of immune checkpoint blockade therapy in the clinic. Here, we review the underlying biology and role of immune checkpoints blockade in patients with MM. Furthermore, we review the host and tumor-related factor effects on immune checkpoints blockade in MM immunotherapy.Tabriz University of Medical SciencesTabriz University of Medical Science