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The novel putative target to the eradication of Acinetobacter baumannii persister cells
No full textBackground: Bacterial persister cells are dormant, slow-growing or growth-arrested phenotypic variants of normal cells in bacterial populations and are suggested that occurrence of the persisters leads to the recalcitrance and relapse of different chronic infections. Acinetobacter baumannii associated-infections are often correlated with high rates of drug-tolerant persisters, triggering a leading human health concern. Methods: In our study, mqsR (as the toxin) and mqsA (as antitoxin) were considered as novel antimicrobial targets and silencing with antisense peptide nucleic acid (PNA) assay to eradicate the A. baumannii persister cells. Firstly, mqsR/A genes were molecularly evaluated. The functionality was assessed by normal and stress conditions in A. baumannii persister cells. Results: Expression of mqsR significantly increased the under stress. A high expression of mqsR TA type II system was detected in A. baumannii persister cells. The mqsR gene fully silenced by PNA and A. baumannii persisters is eradicated. Conclusions: Antisense mqsR-PNA in 15 and 20 μM concentrations could eradicate A. baumannii persister cells. Moreover, it is proposed that other TA loci in A. baumannii are surveyed by antisense PNA to detect their functionality. However, conferring to importance of persisters in human infections, ex vivo, in vivo, preclinical and clinical settings could be highlighted. © 202
Demographic aspects, clinical characteristics, and therapeutic approaches in geriatric psoriasis: A study from a tertiary center
No full textGeriatric psoriasis, due to its unusual clinical manifestations and higher rates of systemic complications in this age group, is a challenging issue for dermatologists. Therefore, we aimed to provide an overview of the epidemiological, clinical, and therapeutic consequences among patients aged over 60 years with psoriasis in a referral center in Iran. This cross-sectional study was conducted on 156 patients over 60 years with the definitive diagnosis of psoriasis that were referred to our center between 2015 and 2019. By reviewing the recorded files of the patients, baseline characteristics including demographics, underlying comorbidities, age of disease onset, clinical type of the disease, clinical manifestations, and therapeutic approaches were extracted. The most common clinical feature was plaque type (73.1) followed by pustular type (10.9). The most frequent involved zone was the lower extremities (84.6). Most of the patients were treated topically (87.1), while as the most frequent systemic approaches, methotrexate and acitretin were considered for 74.4 and 60.3, respectively. A significantly higher mean age at disease onset was found in female patients compared to male patients. The plaque type was more prevalent in men than in women. Also, the chance of nail involvement was 2.43 times higher in men than in women (p = 0.011, 95CI: 1.22�4.84). The disease duration was significantly longer in patients suffering from plaque compared to those without this feature. Conversely, those with palmoplantar type experienced shorter disease duration. Psoriatic arthritis was also revealed in patients of lower ages. As in other societies, in our society, clinical characteristics, disease involvement patterns, as well as considered treatment approaches, can be influenced by demographic characteristics. © 2022 Wiley Periodicals LLC
Cost-effectiveness of fixed-dose combination pill (Polypill) in primary and secondary prevention of cardiovascular disease: A systematic literature review
No full textBackground A significant proportion of cardiovascular disease (CVD) morbidity and mortality could be prevented via the population-based and cost-effective interventions. A fixed-dose combination treatment is known as the polypill for the primary and secondary prevention of CVD has come up in recent years. Purpose In order to provide recommendations for future economic evaluations, this systematic review aimed to review and assess the quality of published evidence on the cost-effectiveness of polypill in primary and secondary prevention of CVD, to identify the key drivers that impact the cost-effectiveness Methods A systematic review of literature, following the PRISMA guidelines, was undertaken in the electronic databases. Two researchers identified the relevant studies according to inclusion and exclusion criteria. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to quality assessment of included studies. ICERs value adjusted to 2020 United States Dollar using consumer price index (CPI) and purchasing power parity (PPP). Finally, data were summarized via a narrative synthesis. Results In total, 24 articles were identified based on the determined inclusion criteria. All studies met more than 50 of the CHEERS criteria. Adjusted incremental cost-effectiveness ratios varied from 24 to 31000(2020 US dollar) among the studies. The polypill resulted in the improved adherence and quality of life, at a price equal to or lower than multiple monotherapies. This price is typically below the commonly accepted thresholds or cost saving in both, primary and secondary prevention of CVD. The main identified cost-effectiveness drivers were the polypill price, adherence, age, CVD risk, and drug combination. Conclusions This systematic review found that the polypill seemed to be a cost-effective intervention in primary and secondary prevention of CVD. However, it is necessary to conduct more economic evaluation studies based on the long-term clinical trials with large populations. Also, studies should consider how the polypill interacts with other primary and secondary preventive strategies as a complementary health strategy. © 2022 Jahangiri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Treatment of EAE mice with Treg, G-MDSC and IL-2: A new insight into cell therapy for multiple sclerosis
No full textBackground: This study investigates the therapeutic and protective effects of Tregs, myeloid-derived suppressor cells (MDSCs) and IL-2 on multiple sclerosis (MS) disease model. Materials & methods: C57BL/6 mice were immunized to develop an experimental autoimmune encephalomyelitis (EAE) model. We then investigated effects of pre- and post-treatment EAE mice with Tregs, MDSCs and IL-2 on inflammation and demyelination in brain tissue, and on the number of Treg, granulocytic-MDSC and Th-17 cells in spleen. Results: Pre- and post-treatment of EAE mice by Tregs, MDSCs and IL-2 resulted in no weight change, reduced Th-17 cells and suppression of pathological properties. Conclusion: Pre- and post-treatment of immunized mice by Tregs, MDSCs and IL-2 prevent EAE induction. Plain language summary This study investigates the therapeutic and protective effects of suppressive immune cells and pivotal cytokines on multiple sclerosis disease model. In this study, mice were immunized to develop experimental autoimmune model. We then investigated effects of pre- and post-treatment model mice with suppressive immune cells and pivotal cytokines on immunomodulatory and pro-inflammatory cells. Pre- and post-treatment of model mice resulted in no weight change, reduced pro-inflammatory cells and suppression of undesired pathological properties. © 2022 Future Medicine Ltd
A Systematic Review on the Economic Evaluations Evidence of Enhanced External Counter-Pulsation (EECP) for Managing Chronic Stable Angina
No full textBackground: Chronic Stable Angina (CSA) does not respond to clinical interventions always. Therefore, enhanced external counter pulsation (EECP) has been approved by the Food and Administration Drug (FDA) as an effective technology. This study aimed to synthesize evidence on the economic evaluation of EECP in managing CSA through a systematic approach. Methods: In this systematic review study, PubMed/Medline, Cochrane Library, Web of Sciences, Scopus, National Institute for Health Research Journals Library, and the University of York Centre for Review and Dissemination (CRD) were searched. The targeted population was people who suffered from CSA, and the main therapeutic intervention was EECP. The comparators were not limited to any particular ones. Outcomes were changes in the Canadian Cardiovascular Society grading of angina pectoris, quality of life, and any other investigated relevant outcomes in the retrieved studies. The quality of studies was assessed through Philips et al and Joanna Briggs Institute Critical Appraisal tools. We synthesized data through a narrative approach. Results: We retrieved 7821 studies; among which 3 studies were included in the final phase. Two studies were systematic reviews and the Markov model economic evaluation. Another study was a partial economic evaluation. Conclusion: All studies only considered direct costs. EECP is a cost-effective technology in managing CSA, however, the sensitivity analysis of the studies showed the cost-effectiveness ratio is varied considerably and further studies are needed to extrapolate its economic value. © 2022. Medical Journal of the Islamic Republic of Iran. All Rights Reserved
Antimicrobial resistance in Vibrio cholerae O1/O139 clinical isolates: a systematic review and meta-analysis
No full textObjectives: Vibrio cholerae O1/O139 is responsible for cholera epidemics that remains a huge public health menace across the globe. Furthermore, an increasing resistance rate among V. cholerae strains has been reported around the world. Therefore, the objective of this meta-analysis was to evaluate the weighted pooled resistance (WPR) rates in clinical V. cholerae O1/O139 isolates based on different years, areas, antimicrobial susceptibility testing, and resistance rates. Research design and methods: We searched the studies in PubMed, Scopus, Embase, and Web of Science (until January 2020). Statistical analyses were conducted using STATA software (ver. 14.0). Results: A total of 139 studies investigating 24,062 V. cholerae O1/O139 isolates were analyzed. The majority of the studies originated in Asia (n = 102). The WPR rates were as follows: azithromycin 1, erythromycin 36, ciprofloxacin 3, cotrimoxazole 79, doxycycline 7, and tetracycline 20. There was increased resistance to cotrimoxazole, ciprofloxacin, and tetracycline during the 1980�2020 years. Conclusions: Temporal changes in antibiotic resistance rate found in this study demonstrated the critical continuous surveillance of antibiotic resistance. Also, ciprofloxacin, azithromycin, gentamicin, cephalexin, imipenem, ofloxacin, and norfloxacin were found to be the best antibiotics against V. cholera, with the highest and the lowest effectiveness resistance rate. © 2022 Informa UK Limited, trading as Taylor & Francis Group
Statistical modeling optimization for antibiotics decomposition by ultrasound/electro-Fenton integrated process: Non-carcinogenic risk assessment of drinking water
No full textThe present work proposes an ultrasound (US) assisted electro-Fenton (EF) process for eliminating penicillin G (PNG) and ciprofloxacin (CIP) from aqueous solutions and the process was further optimized by response surface methodology (RSM)- Box-Behnken design (BBD). The impact of pH, hydrogen peroxide (H2O2) concentration, applied voltage, initial pollutant concentration, and operating time were studied. The capability application of the electro-Fenton (EF) and US processes was compared separately and in combination under the optimum conditions of pH of 4, a voltage of 15 V, the initial antibiotic concentration of 20.7 mg/L, H2O2 concentration of 0.8 mg/L, and the operating time of 75 min. The removal efficiency of PNG and CIP using the sono-electro-Fenton (SEF) process, as the results revealed, was approximately 96 and 98, respectively. The experiments on two scavengers demonstrated that �OH contributes significantly to the CIP and PNG degradation by SEF, whereas �O�2 corresponds to only a negligible amount. The total organic carbon (TOC) and chemical oxygen demand (COD) analyses were used to assess the mineralization of CIP and PNG. The efficiency of COD and TOC removal was reached at 73.25 and 62.5 for CIP under optimized operating circumstances, and at 61.52 and 72 for PNG, respectively. These findings indicate that a sufficient rate of mineralization was obtained by SEF treatment for the mentioned pollutants. The reaction kinetics of CIP and PNG degradation by the SEF process were found to follow a pseudo-first-order kinetic model. In addition, the human health risk assessment of natural water containing CIP and PNG that was purified by US, EF, and SEF processes was done for the first time. According to the findings, the non-carcinogenic risk (HQ) caused by drinking purified water by all three systems was calculated in the acceptable range. Thus, SEF is a proper system to remove various antibiotics in potable water and reduces their human health risks. © 202
Anesthesia and analgesia for common research models of adult mice
No full textAnesthesia and analgesia are major components of many interventional studies on laboratory animals. However, various studies have shown improper reporting or use of anesthetics/analgesics in research proposals and published articles. In many cases, it seems �anesthesia� and �analgesia� are used interchangeably, while they are referring to two different concepts. Not only this is an unethical practice, but also it may be one of the reasons for the proven suboptimal quality of many animal researches. This is a widespread problem among investigations on various species of animals. However, it could be imagined that it may be more prevalent for the most common species of laboratory animals, such as the laboratory mice. In this review, proper anesthetic/analgesic methods for routine procedures on laboratory mice are discussed. We considered the available literature and critically reviewed their anesthetic/analgesic methods. Detailed dosing and pharmacological information for the relevant drugs are provided and some of the drugs� side effects are discussed. This paper provides the necessary data for an informed choice of anesthetic/analgesic methods in some routine procedures on laboratory mice. © 2022, The Author(s)
Cuscuta epithymum Murr. crude extract pre-conditioning protects C6 cells from L-glutamate-induced neurotoxicity
No full textBackground: Cuscuta epithymum Murr. (C. epithymum), as an herbal medicine, has played an anti-cancerous role in various studies; however, its possible neuroprotective effects have been neglected. Here, we aimed to investigate the protective effects of C. epithymum seeds crude extract and different fractions on rat glioblastoma cells (C6) in L-glutamate oxidative condition. Methods: Initially, the total phenolic content of C. epithymum crude extract and the fractions (all produced by maceration method) was determined. Subsequently, C6 cells were pre-treated with the various concentrations of crude extract and fractions 24 h before L-glutamate exposure. Likewise, C6 cells were treated with the same concentrations of crude extract and fractions 24 h after exposure to L-glutamate. The cell viability and morphology were compared in crude extract and fractions groups, then superoxide dismutase (SODs) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) levels were measured. The flow cytometry test was used to study C. epithymum crude extract's effects on the cell cycle and also to quantify the apoptosis, necrosis, and live cells population in different groups. Results: C. epithymum crude extract and fractions (hexanoic, dichloromethanolic, and methanolic) had concentration-dependent cytotoxicity (IC50:126.47, 2101.96, 140.97, and 218.96 µg/ml, respectively). The crude extract and methanolic fraction contained phenolic compounds (55.99 ± 2.795 and 50.80 ± 2.969 mg gallic acid/g extract), while in hexanoic and dichloromethanolic fractions, the phenolic content was undetectable. In the cell viability assay, in comparison to fractions, the crude extract showed a more protective effect against glutamate-induced oxidative condition (P < 0.0001). The crude extract increased the SODs activity (P < 0.001) and decreased MDA and ROS levels (P < 0.0001) in comparison to the glutamate group. The crude extract significantly increased the population of cells in G1 (from 63.04 to 76.29) and decreased the percentage of cells in G2 (from 11.56 to 6.7) and S phase (from 25.4 to 17.01). In addition, it decreased the apoptotic and necrotic cell populations (from 34 to 17.1) and also increased the percentage of live cells (from 66.8 to 83.4 percent) in the flow cytometry test. Conclusion: C. epithymum crude extract plays a neuroprotective role by activating the defense mechanisms in cell against the oxidative condition. © 2022, The Author(s)
HIV testing among incarcerated people with a history of HIV-related high-risk behaviours in Iran: Findings from three consecutive national bio-behavioural surveys
No full textBackground: Incarcerated people are at a disproportionate risk of contracting HIV. We estimated the prevalence and correlates of HIV testing among incarcerated people with a history of HIV-related high-risk behaviours in Iran. Methods: Data for this analysis were obtained from three consecutive nationwide bio-behavioural surveillance surveys of a random sample of incarcerated people in 2009 (n = 5953), 2013 (n = 5490), and 2017 (n = 5785). History of testing for HIV in the last 12 months was the primary outcome variable. HIV testing was examined among those with a history of HIV-related high-risk behaviours (i.e., having multiple sex partnerships, injection drug use practices, or a history of having a tattoo). The outcome variable was divided into three categories: Never tested for HIV, ever tested for HIV inside the prison in the last 12 months, and ever tested for HIV outside the prison in the last 12 months. We used multivariable multinomial logistic regression models to examine factors associated with HIV testing. Results: Overall, 8,553 participants with a history of HIV-related high-risk behaviors with valid responses to the HIV testing question were included in the analysis. Although HIV testing inside prison has increased (23 2009, 21.5% 2013, and 50.3% 2017: P-value < 0.001), the prevalence of HIV testing outside prison has decreased (7.7% 2009, 7.5% 2013, 4.1% 2017: P-value < 0.001) over time. Our multivariable multinomial regression model showed older age (Relative-risk ratio RRR: 1.24, 95% Confidence Intervals CI: 1.05, 1.47), history of the previous incarceration (RRR: 1.46, 95% CI: 1.24, 1.71), currently receiving methadone maintenance therapy inside prison (RRR: 2.09, 95% CI: 1.81, 2.43), having access to condoms inside prison (RRR: 1.42, 95% CI: 1.20, 1.68) and sufficient HIV knowledge (RRR: 1.74, 95% CI: 1.47, 2.05) were significantly associated with an increased probability of having an HIV test in the last 12 months inside prison. Conclusion: HIV testing among high-risk Iranian prisoners has increased from 2009 to 2017. However, HIV testing remains considerably low, and half of the incarcerated people with a history of HIV-related high-risk behaviours had never tested for HIV inside prison. Evidence-based programs are needed to optimize HIV testing inside and outside prisons and identify those at greater risk of HIV. © 2022, The Author(s)