Ralstoniapickettii 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.

Toxoplasma gondii infection in domestic and wild felids as public health concerns: a systematic review and meta-analysis.

Felidae as definitive hosts for Toxoplasma gondii play a major role in transmission to all warm-blooded animals trough oocysts dissemination. Therefore the current comprehensive study was performed to determine the global status of T. gondii infection in domestic and wild felids aiming to provide comprehensive data of interest for further intervention approaching the One Health perspective. Different databases were searched by utilizing particular key words for publications related to T. gondii infecting domestic and wild feline host species, worldwide, from 1970 to 2020. The review of 337 reports showed that the seroprevalence of T. gondii in domestic cats and wild felids was estimated in 37.5% (95% CI 34.7-40.3) (I2 = 98.3%, P < 0.001) and 64% (95% CI 60-67.9) (I2 = 88%, P < 0.0001), respectively. The global pooled prevalence of oocysts in the fecal examined specimens from domestic cats was estimated in 2.6% (95% CI 1.9-3.3) (I2 = 96.1%, P < 0.0001), and that in fecal samples from wild felids was estimated in 2.4% (95% CI 1.1-4.2) (I2 = 86.4%, P < 0.0001). In addition, from 13,252 examined soil samples in 14 reviewed studies, the pooled occurrence of T. gondii oocysts was determined in 16.2% (95% CI 7.66-27.03%). The observed high rates of anti-T. gondii antibodies seroprevalence levels and oocyst excretion frequency in the felids, along with soil (environmental) contamination with oocysts may constitute a potential threat to animal and public health, and data will result of interest in further prophylaxis programs.

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.

Pediculosis capitis among school-age students worldwide as an emerging public health concern: a systematic review and meta-analysis of past five decades.

Pediculosis by Pediculus humanus capitis is still an important health issue in school-age students worldwide. Although pediculicidal agents effectively kill head lice, the re-infestation rate is still high. This study was conducted to provide a summary of evidence about the prevalence of pediculosis capitis among school-age students worldwide. Different databases including MEDLINE/PubMed, Scopus, and Web of Science were searched for publications related to pediculosis capitis in school-age students from 1977 to 2020. All peer-reviewed original research articles describing pediculosis capitis among school-age students were included. Statistical heterogeneity of the different years among studies was assessed using the standard chi squared and I2 tests. Due to the significant heterogeneity, a random effect model was adopted to estimate the pooled, continent, and gender-specific prevalence of pediculosis. Two hundred and one papers met the inclusion criteria of this review and entered into the meta-analysis including 1,218,351 individuals. Through a random effect model, the prevalence of pediculosis capitis among school students was estimated as 19% (CI 95% = 0.18-0.20%, I2 = 99.89%). The prevalence of pediculosis capitis among boys was 7% (CI 95% = 0.05-0.10) compared to 19% (CI 95% = 0.15-0.24) in girls. The highest prevalence was in Central and South America (33%, CI 95% = 0.22-0.44, I2 = 99.81%) and the lowest was in Europe (5%, CI 95% = 4-6, I2 = 99.28%). Relatively high pediculosis capitis prevalence among school-age students observed in this study emphasizes the need for implementing screening and prophylaxis tailored to the local context.

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.

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.

Global Prevalence and Device Related Causes of Needle Stick Injuries among Health Care Workers: A Systematic Review and Meta-Analysis.

Background: Healthcare workers (HCWs) suffer more than 2 million occupational needle-stick injuries (NSIs) annually. Goal: To determine the global prevalence and causes of NSIs among HCWs. Methods: In this systematic review and meta-analysis, three databases (PubMed, Web of science, and Scopus) were searched for reports from January 1, 2000 to December 31, 2018. The random effects model was used to determine the prevalence of NSIs among HCWs. Hoy et al.'s instrument was employed to evaluate the quality of the included studies. Findings: A total of 87 studies performed on 50,916 HCWs in 31 countries worldwide were included in the study. The one-year global pooled prevalence of NSIs among HCWs was 44.5% (95% CI: 35.7, 53.2). Highest prevalence of NSIs occurred in the South East Asia region at 58.2% (95%, CI: 36.7, 79.8). By job category, prevalence of NSIs was highest among dentists at 59.1% (95% CI: 38.8, 79.4), Hypodermic needles were the most common cause of NSIs at 55.1% (95% CI: 41.4, 68.9). Conclusion: The current high prevalence of NSIs among HCWs suggests need to improve occupational health services and needle-stick education programs globally.