Investigating the sequential patterns of methamphetamine use initiation in Iran

BACKGROUND: Methamphetamine (MA) remains one of the most commonly used amphetamine-type stimulants, accounting for the second most widely-used substance after marijuana. Due to increased use of MA, a wide variety of research has focused on the patterns of MA use initiation among adolescents. Nevertheless, there are few data available for people who use MA. The present study set out to assess the sequential patterns of substance use initiation in patients with MA use disorders in Iran. MATERIALS AND METHODS: This cross-sectional study described substance initiation patterns for 302 patients who used MA admitted to hospitals and psychiatric centers of Shiraz University of Medical Sciences. The study was conducted between April 2015 and June 2016. After obtaining informed consents, participants were interviewed by trained interviewers using face-to-face, semi-structured interviews. The collecting data were analyzed using the chi square tests and one-way analysis of variance (ANOVA) tests to compare the relationship between qualitative and quantitative variables, respectively. RESULTS: Out of 302 participants enrolled in the study, 16 (5.3%) and 286 (94.7%) were female and male, respectively. The mean age of participants in the study was 37.29 years. The mean age of onset of MA use was found to be 15.9 years. 46.1% of the patients started MA use before 15 years. 77.2% of the patients who used MA had family members with a history of substance use. 93.71% of the patients who used MA started substance use with tobacco, alcohol, or opium, as the most frequent substances. Tobacco, as the first substance or starting substance, exhibited the most widely-used substance (69.53% of the cases). Tobacco-alcohol-cannabis-opium-heroin-MA sequencing was significantly related to the early onset of the substance use. Early-onset substance use was significantly higher in those with lower income, primary education, and family history of substance use. No significant relationship was found between employment status with the age of onset of substance use, and different substance use with marital status. CONCLUSION: Tobacco, alcohol and opium can be considered as the main sequencing substances for initiation to MA use. Standardized measures to decrease and control access to main starting and sequencing substances, including tobacco, alcohol, and opium, can greatly help decrease the early onset of the MA use, develop suitable prevention, and establish early intervention strategies

Ralstonia pickettii bloodstream infection in the patient with Guillain-Barre syndrome under plasmapheresis

Ralstonia pickettii is a rare Gram-negative opportunistic bacterium that causes rare infections such as bacteremia, neonatal sepsis, endocarditis, and meningitis in hospitalized or immunocompromised patients. In this study, we identified and reported bloodstream infection caused by R. pickettii in a 15 -year-old boy patient with an autoimmune disease, Guillain-Barré syndrome, under plasmapheresis and intravenous immune globulin (IVIG) therapy. He was referred for admission to the neurology center of the teaching hospital of Shiraz, Iran for inability to walk, and lower extremity muscle weakness. After he was treated with plasmapheresis once during hospitalization, and after severe fever besides shivering blood cultures using BACT/ALERT®3D instrument were positive for R. pickettii. According to antibiotic susceptibility test reports, Ciprofloxacin (5 μg) was prescribed. Fortunately, after starting antibiotic treatment, blood culture results reported no growth after 5 days. Indeed, the patient was infected with nosocomial hepatitis A and URSOBIL (300 mg/BID/Po) was administered. Hence, after reporting the infection occurrence to the hospital infection control unit, initial and possible measures such as device infection control, replacement of potentially polluted plasmapheresis fluids, disinfecting the environment and replacing old sterile washing water with new sources were carried out in plasmapheresis unit. In conclusion, R. pickettii is a rare nosocomial infection that is responsible for the contamination of medical equipment, especially in hemodialysis, plasmapheresis devices and sterile solutions. Also, it is suggested that the role and importance of rare environmental bacteria as the causative agents of human infections should not be ignored in medical centers

Development and biological assessment of MMAE-trastuzumab antibody-drug conjugates (ADCs)

Background: Trastuzumab, a humanized monoclonal antibody targeting Human Epidermal growth factor Receptor 2 (HER2), is a therapeutic option used for the treatment of patients with HER2-overexpressing breast cancers. The primary purpose of the present study was to establish a trastuzumab-based antibody drug conjugate (ADC) to enhance the biopharmaceutical profile of trastuzumab. Methods: In this study, trastuzumab was linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) through a peptide linker. Following conjugation, MMAE-trastuzumab ADCs were characterized using SDS-PAGE, UV/VIS, and cell-based ELISA. The inhibitory effects of the ADCs were measured on MDA-MB-453 (HER2-positive cells) and HEK-293 (HER2-negative cells) using in vitro cell cytotoxicity and colony formation assays. Results: Our findings showed that approximately 3.4 MMAE payloads were conjugated to trastuzumab. MMAE-trastuzumab ADCs produced six bands, including H2L2, H2L, HL, H2, H, and L in non-reducing SDS-PAGE. The conjugates exhibited the same binding ability to MDA-MB-453 as unconjugated trastuzumab. The MTT assay showed a significant improvement in the trastuzumab activity following MMAE conjugation, representing a higher antitumor activity as compared with unconjugated trastuzumab. Furthermore, ADCs were capable of potentially inhibiting colony formation in HER2-positive cells, as compared with trastuzumab. Conclusion: MMAE-trastuzumab ADCs represent a promising therapeutic strategy to treat HER2-positive breast cancer

Key Regulatory miRNAs and their Interplay with Mechanosensing and Mechanotransduction Signaling Pathways in Breast Cancer Progression

According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (∼22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells