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Background CervixCheck, Manitoba's cervical cancer screening program, conducted a pilot study to assess whether screening participation could be improved in unscreened women by offering a mailed self-sampling kit for human papillomavirus (hpv) testing instead of a Pap test. Methods In a prospective cohort study design, a sample of unscreened women (n = 1052) who had been sent an invitation letter from CervixCheck in the past but who did not respond were randomized to either an intervention group or a control group. The intervention group received a mailed hpv self-sampling kit; the control group received no additional communication. Returned hpv self-sampling swabs were analyzed by a provincial laboratory. After 6 months, screening participation in the two study groups was compared using a logistic regression model adjusted for age and area of residence (urban or rural). Secondary outcomes included hpv positivity, specimen inadequacy, compliance with follow-up, and time to colposcopy. Results Screening participation was significantly higher in the intervention group than in the control group (n = 51, 9.6%, vs. n = 13, 2.5%; odds ratio: 4.7; 95% confidence interval: 2.56 to 8.77). Geographic area of residence (urban or rural) and age were not statistically significant. Conclusions The study demonstrated that hpv self-sampling kits can enhance screening participation in unscreened non-responder women in the setting of an organized screening program. Next steps should include additional research to determine the best implementation strategy for hpv self-sampling in Manitoba. [ABSTRACT FROM AUTHOR]

Methyl tertiary-butyl ether is a synthetic compound that was developed as a technological solution to a technology-derived problem created by air pollution from vehicle emissions. Methyl tertiary-butyl ether was added to gasoline with the intent to reduce air emissions, making the fuel burn cleaner. Unfortunately, use of this air-saving gasoline additive has created one of the most threatening and widespread environmental problems for the nation's drinking water supply. In this work, degradation of methyl tertiary-butyl ether in aqueous solution using the solar ultraviolet and TiO2nano particles was investigated. Factors that affect photocatalytic removal of methyl tertiary-butyl ether, such as pH, TiO2, and methyl tertiary-butyl ether concentrations, were studied and optimum conditions were determined using the Taguchi method for designing the experiments. Results showed that the best conditions for the removing of methyl tertiary-butyl ether in the ultraviolet/TiO2process are 2 g/l nano TiO2and 50 ppm methyl tertiary-butyl ether, which leads to more than 88% removal of methyl tertiary-butyl ether in 120 min. [ABSTRACT FROM PUBLISHER]

Background Although the concept that an initial course of immune-suppression facilitates subsequent immune-modulation (such as Th1 to Th2 deviation) is attractive for several autoimmune diseases, such a mechanism for serial-combination therapy has never been formally demonstrated. Recently, brief mitoxantrone induction-chemotherapy followed by immune-modulation with glatiramer acetate (GA) was significantly more effective at reducing multiple sclerosis disease activity than with GA alone. Objective To examine whether the benefit of initial immune suppression with mitoxantrone before GA treatment is associated with more efficient immune modulation. Methods IgG1/IgG4 GA-reactive antibody profiles, previously established as markers of GA-induced Th2 immune-deviation, were prospectively measured in vivo in patients treated with GA alone or with mitoxantrone induction therapy followed by GA. Results Significant and sustained increase in IgG4 antibodies (and the anticipated reversal of the IgG1/IgG4 ratio) was seen in patients treated with GA alone. Combination therapy resulted in lesser IgG4 induction (and no reversal of IgG1/IgG4 ratio). Thus, the enhanced efficacy of mitoxantrone--GA combination regimen was associated with decreased, rather than increased, efficiency of shifting the GA-reactive IgG1/IgG4 antibody profile. Conclusion These results provide important insights into mechanisms of combination therapy and therapeutic strategies for autoimmune diseases. [ABSTRACT FROM AUTHOR]

Dowex 1-X8, as a quaternary ammonium resin, on which CI- ⇒ Cl- is replaced by dichromate and bisulfate ions (DDB), can be used as a stable and efficient oxidizing reagent for oxidative selection between benzylic alcohols according to their structures. [ABSTRACT FROM AUTHOR]

Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL-6 plasma level and cardiac biomarker NT-proBNP, HS-CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL-6 and NT-proBNP plasma levels were measured by the ELISA. Also, HS-CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL-6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL-6 with DAS-28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = -0.270), in the patients. Also, IL-6 plasma level positively correlated with HS-CRP (p = 0.021, r = 0.297) and NT-proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL-6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL-6 with various variables of CVD, IL-6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objectives: We conducted a systematic review and meta-analysis to evaluate the association between neighborhood socioeconomic status (n-SES) and the risk of incidence and mortality in colorectal cancer (CRC)., Setting: A comprehensive literature search was performed using PubMed/MEDLINE, ISI Web of Science and Scopus without any limitation until October 11, 2023. Inclusion criteria consisted of observational studies in adult subjects (≥18 years) which provided data on the association between n-SES and CRC-related incidence and mortality. Relative risk (RR) and 95 % confidence interval (CI) were pooled by employing a random-effects model. We employed validated methods to assess study quality and publication bias, utilizing the Newcastle-Ottawa Scale for quality evaluation, subgroup analysis to find possible sources of heterogeneity, Egger's regression asymmetry and Begg's rank correlation tests for bias detection and sensitivity analysis., Results: Finally, 24 studies (21 cohorts and 3 cross-sectional studies) from seven different countries with 1678,582 participants were included. The analysis suggested that a significant association between lower n-SES and an increased incidence of CRC (RR=1.11; 95 % CI: 1.08, 1.14; I 2 =64.4 %; p<0.001; n=46). The analysis also indicated a significant association between lower n-SES and an increased risk of mortality of CRC (RR=1.21; 95 % CI: 1.16, 1.26; I 2 =76.4 %; p<0.001; n=23). Furthermore, subgroup analysis revealed that there was a significant association between lower n-SES and an increased risk of incidence of CRC in colon location (RR=1.06; 95 % CI: 1.02, 1.10; I2=0.0 %; p=0.001; n=8), but not rectal location. In addition, subgroup analysis for covariates adjustment suggested that body mass index, smoking, physical activity, alcohol intake, or sex adjustment may influence the relationship between n-SES and the risk of incidence and mortality in CRC., Conclusion: Lower n-SES was found to be a contributing factor to increased incidence and mortality rates associated with CRC, highlighting the substantial negative impacts of lower n-SES on cancer susceptibility and health outcomes., Competing Interests: Declaration of Competing Interest Faramarz Jalili, Mohammad Hajizadeh, Sanaz Mehrabani, Seyed Mojtaba Ghoreishy, Felicity MacIsaac: No conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The present systematic review and dose-response meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of citrus flavonoids supplementation (CFS) on endothelial function. Relevant RCTs were identified through comprehensive searches of the PubMed, ISI Web of Science, and Scopus databases up to May 30, 2023. Weighted mean differences and their corresponding 95% confidence intervals (CI) were pooled utilizing a random-effects model. A total of eight eligible RCTs, comprising 596 participants, were included in the analysis. The pooled data demonstrated a statistically significant augmentation in flow-mediated vasodilation (FMD) (2.75%; 95% CI: 1.29, 4.20; I 2  = 87.3%; p < 0.001) associated with CFS compared to the placebo group. Furthermore, the linear dose-response analysis indicated that each increment of 200 mg/d in CFS led to an increase of 1.09% in FMD (95% CI: 0.70, 1.48; I 2  = 94.5%; p < 0.001). The findings from the nonlinear dose-response analysis also revealed a linear relationship between CFS and FMD (P non-linearity  = 0.903, P dose-response  <0.001). Our findings suggest that CFS enhances endothelial function. However, more extensive RTCs encompassing longer intervention durations and different populations are warranted to establish more precise conclusions., (© 2024 John Wiley & Sons Ltd.)

Aflatoxins (AFs) are inevitable environmental contaminants that are detrimental to human and animal health. AFs interfere with metabolic processes, metabolizing into different hydroxylated derivatives in the liver, as well as mechanistically induce ROS accumulation, S-phase arrest, DNA damage, and cell apoptosis. Chronic consumption of aflatoxin-contaminated foods can adversely affect the male reproductive system, cause testicular damage, prevent testosterone synthesis, decline sperm quality, and cause infertility. Oxidative stress is the fundamental pathogenesis of aflatoxin-induced reproductive toxicity. The overproduction of reactive oxygen substances can cause testicular failure and disturb the process of spermatogenesis. Mitochondria are susceptible to being impaired by oxidative stress, and its damage is associated with infertility. AFs also disturb the process of spermatogenesis by disrupting the regulation of genes related to the progression of the cell cycle such as cyclins and inducing genes related to apoptosis, thereby weakening fertility and negatively affecting the testicular endocrine potential by suppressing androgen synthesis. Additionally, AFs downregulate ERα expression, potentially negatively impacting spermatogenesis by enhancing the apoptotic mechanism. In this review, we provide new insights into the genotoxic and cytotoxic effects of AFB1 on the male reproductive system with a focus on the cell cycle and apoptosis destruction of testicular tissue., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: People with disabilities (PWD) have different health service needs and different factors affect the utilization of these services. Therefore, the aim of this present study was to identify determinants of inpatient healthcare utilization among PWDs in Iran., Methods: This research was a secondary data analysis of a cross-sectional study. The present study used data gathered for 766 PWDs (aged 18 years and older) within the Iranian Society with Disabilities (ISD) between September and December 2020. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals in order to identify determinants of inpatient healthcare utilization among PWDs., Results: Data for 766 people with disabilities were analyzed. A large number of participants were over 28 years of age (70.94%), male (64.36%), and single (54.02%). In the present study, more than 71% of participants had no history of hospitalization during the last year. In this study, males [aOR 2.11(1.14-3.91), participants with Civil Servants health insurance coverage [aOR 3.44 (1.16 - 10.17)] and individuals in the 3th quartile of disability severity [aOR 2.13 (1.01 - 4.51)] had greater odds of inpatient healthcare utilization compared to the other groups. The value of the concentration index (C) for inpatient healthcare utilization was - 0.084 (P.value = 0.046). The decomposition analysis indicated that gender was the greatest contributor (21.92%) to the observed inequality in inpatient healthcare utilization among participants., Conclusion: Our findings suggested that the likelihood of hospitalization among the study participants could be significantly influenced by factors such as gender, the health insurance scheme, and the degree of disability severity. These results underscore the imperative for enhanced access to outpatient services, affordable insurance coverage, and reduced healthcare expenditures for this vulnerable population. Addressing these issues has the potential to mitigate the burden of hospitalization and promote better health outcomes for disadvantaged individuals., (© 2024. The Author(s).)

The prevalence of hyperlipidemia has increased dramatically worldwide. It is a major public health threat, characterized by the presence of an abnormal lipid profile, primarily with elevated serum total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) levels, and reduced high-density lipoprotein (HDL) level. Genetic factors, dietary and lifestyle habits play important roles in hyperlipidemia. It can increase the risk of chronic metabolic disorders, such as obesity, cardiovascular disease, and type II diabetes. The main objective of the present study was to evaluate the effect of urazine derivatives on serum triglyceride, cholesterol, LDL, HDL, and nitric oxide (NO) levels in high-fat diet (HFD)-induced hyperlipidemic rats. Synthetic compounds were prepared and confirmed by spectroscopic methods. Then, 88 male Sprague-Dawley rats were divided into 11 groups: control, HFD-treated group, HFD plus atorvastatin-treated group, and HFD plus 8 synthetic compounds-treated groups. The body weight, triglyceride, cholesterol, LDL, HDL, and NO levels were measured. The data with p < 0.05 were considered significant. The results indicated that HFD significantly increased cholesterol, triglyceride, and LDL levels and decreased NO concentration and HDL level compared to the control group (p < 0.05). However, HFD plus urazine derivatives significantly decreased NO, cholesterol, and triglyceride levels and increased HDL levels compared to the HFD-treated group (p < 0.05). Urazine derivatives may improve liver dysfunction in HFD-induced hyperlipidemic rats by modulation of detoxification enzymes and their anti-oxidant effects and also blood lipid profile., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The Health Sector Evolution Plan (HSEP) was set up in Iran's health system to respond to some of the main problems in hospitals and other health sectors. We aimed to compare the effect of the HSEP on teaching hospital performance before and after the implementation of the HSEP through the interrupted time series (ITS) analysis., Methods: With a cross-sectional design, data collection was performed in 17 teaching hospitals affiliated with the Kermanshah University of Medical Sciences (KUMS). We used the existing data on three indicators of hospitalization rate (per 10,000 population), Emergency Department Visits (EDVs) (per 10,000 population), and in-hospital mortality (per 10,000 population). The monthly data from 2009 to 2019 was analyzed by the ITS method 60 months before and 61 months after the HSEP., Results: We found a non-statistically significant decrease in the monthly trend of hospitalization rate relative to the period before the HSEP implementation (-0.084 per 10,000 population [95%CI: -0.269, 0.101](. There was a statistically significant increase in the monthly trend of EDVs rate compared to before the HSEP implementation (1.07 per 10,000 population [95%CI: 0.14, 2.01]). Also, a significant decrease in the monthly trend of in-hospital mortality compared to before the HSEP implementation [-0.003 per 10,000 population (95%CI: -0.006, -0.001)] was observed., Conclusion: Our study demonstrated a significant increasing and decreasing trend for EDVs and in-hospital mortality following the HSEP implementation, respectively. Regarding the increase in hospitalization rate and EDVs after the implementation of HESP, it seems that there is a need to increase investment in healthcare and improve healthcare infrastructure, human resources-related indicators, and the quality of healthcare., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Soltani, Rezaei, Kazemi-Karyani, Azimi, Jalili, Roshani, Najafi, Bagheri and Salimi.)

Previous studies have advocated that collagen peptide supplementation (CPS) can positively affect cardiovascular health. However, the widespread impact of CPS on CVD-related markers is not fully resolved. Consequently, the current systematic review and meta-analysis aimed to assess the efficacy of CPS on CVD-related markers. A systematic search in the Scopus, PubMed and ISI Web of Science databases were completed to identify relevant randomised, placebo-controlled trials (RCT) published up to November 2021. Mean Differences were pooled using a random-effects model, while publication bias, sensitivity analyses and heterogeneity were assessed using previously validated methods. Twelve RCT, comprising of a total of eleven measured markers, were selected for the quantitative analysis. Pooled data revealed that CPS significantly decreased fat mass (-1·21 kg; 95 % CI: -2·13, -0·29; I 2 = 0·0 %; P = 0·010) and increased fat-free mass, based on body mass percentage (1·49 %; 95 % CI: 0·57, 2·42; I 2 = 0·0 %; P = 0·002). Moreover, collagen peptide supplementation led to a significant decrease in serum LDL (-4·09 mg/dl; 95 % CI: -8·13, -0·04; I 2 = 93·4 %; P = 0·048) and systolic blood pressure (SBP) (-5·04 mmHg; 95 % CI: -9·22, -0·85; I 2 = 98·9 %; P = 0·018). Our analysis also indicated that CPS did not affect glycemic markers. Our outcomes indicate that CPS reduces fat mass, LDL and SBP while increasing fat-free mass. Future investigations with longer CPS duration are needed to expand on our results.

Health-related concerns about cyanobacteria-laden sludge of drinking water treatment plants (DWTPs) have been raised in the past few years. Microscopic taxonomy, shotgun metagenomic sequencing, and microcystin (MC) measurement were applied to study the fate of cyanobacteria and cyanotoxins after controlled sludge storage (stagnation) in the dark in a full-scale drinking water treatment plant within 7 to 38 days. For four out of eight dates, cyanobacterial cell growth was observed by total taxonomic cell counts during sludge stagnation. The highest observed cell growth was 96% after 16 days of stagnation. Cell growth was dominated by potential MC producers such as Microcystis , Aphanocapsa , Chroococcus , and Dolichospermum . Shotgun metagenomic sequencing unveiled that stagnation stress shifts the cyanobacterial communities from the stress-sensitive Nostocales (e.g., Dolichospermum ) order towards less compromised orders and potential MC producers such as Chroococcales (e.g., Microcystis ) and Synechococcales (e.g., Synechococcus ). The relative increase of cyanotoxin producers presents a health challenge when the supernatant of the stored sludge is recycled to the head of the DWTP or discharged into the source. These findings emphasize the importance of a strategy to manage cyanobacteria-laden sludge and suggest practical approaches should be adopted to control health/environmental impacts of cyanobacteria and cyanotoxins in sludge., Competing Interests: The authors declare no conflict of interest.

Cardiovascular disease (CVD) is a major concern for health with high mortality rates around the world. CVD is often associated with partial or full occlusion of the blood vessel network. Changes in lifestyle can be useful for management early-stage disease but in the advanced stage, surgical interventions or pharmacological are needed to increase the blood flow through the affected tissue or to reduce the energy requirements. Regeneration medicine is a new science that has provided many different options for treating various diseases, especially in CVD over the years. Stem cell therapy, gene therapy, and tissue engineering are some of the powerful branches of the field that have given patients great hope in improving their condition. In this review, we attempted to examine the beneficial effects, challenges, and contradictory effects of angiogenesis in vivo, and in vitro models' studies of CVD. We hope that this information will be able to help other researchers to design new effective structures and open new avenues for the treatment of CVD with the help of angiogenesis and regeneration medicine in the future., Competing Interests: None declared., (©2022 The Authors.)

Freshwater bodies and, consequently, drinking water treatment plants (DWTPs) sources are increasingly facing toxic cyanobacterial blooms. Even though conventional treatment processes including coagulation, flocculation, sedimentation, and filtration can control cyanobacteria and cell-bound cyanotoxins, these processes may encounter challenges such as inefficient removal of dissolved metabolites and cyanobacterial cell breakthrough. Furthermore, conventional treatment processes may lead to the accumulation of cyanobacteria cells and cyanotoxins in sludge. Pre-oxidation can enhance coagulation efficiency as it provides the first barrier against cyanobacteria and cyanotoxins and it decreases cell accumulation in DWTP sludge. This critical review aims to: (i) evaluate the state of the science of cyanobacteria and cyanotoxin management throughout DWTPs, as well as their associated sludge, and (ii) develop a decision framework to manage cyanobacteria and cyanotoxins in DWTPs and sludge. The review identified that lab-cultured-based pre-oxidation studies may not represent the real bloom pre-oxidation efficacy. Moreover, the application of a common exposure unit CT (residual concentration × contact time) provides a proper understanding of cyanobacteria pre-oxidation efficiency. Recently, reported challenges on cyanobacterial survival and growth in sludge alongside the cell lysis and cyanotoxin release raised health and technical concerns with regards to sludge storage and sludge supernatant recycling to the head of DWTPs. According to the review, oxidation has not been identified as a feasible option to handle cyanobacterial-laden sludge due to low cell and cyanotoxin removal efficacy. Based on the reviewed literature, a decision framework is proposed to manage cyanobacteria and cyanotoxins and their associated sludge in DWTPs.

In the current paper, we produce a new metal-organic framework (MOF) based on Zr metal, [Zr-UiO-66-PDC-SO 3 H]FeCl 4 , via an anion exchange method, which is fully characterized by FT-IR, SEM with elemental mapping and EDX, FE-SEM and TEM. Furthermore, the use of [Zr-UiO-66-PDC-SO 3 H]FeCl 4 as a porous catalyst was examined for the one-pot synthesis of novel dihydrobenzo[ g ]pyrimido[4,5- b ]quinoline derivatives by reaction of 6-amino-1,3-dimethylpyrimidine-2,4(1 H ,3 H )-dione, 2-hydroxynaphthalene-1,4-dione and various aldehydes at 100 °C with good to excellent yields., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Neurodegenerative diseases are questions that modern therapeutics can still not answer. Great milestones have been achieved regarding liver, heart, skin, kidney and other types of organ transplantations but the greatest drawback is the adequate supply of these organs. Furthermore, there are still a few options available in the treatment of neurodegenerative diseases. With great advances in medical science, many health problems faced by humans have been solved, and their quality of life is improving. Moreover, diseases that were incurable in the past have now been fully cured. Still, the area of regenerative medicine, especially concerning neuronal regeneration, is in its infancy. Presently allopathic drugs, surgical procedures, organ transplantation, stem cell therapy forms the core of regenerative therapy. However, many times, the currently used therapies cannot completely cure damaged organs and neurodegenerative diseases. The current review focuses on the concepts of regeneration, hurdles faced in the path of regenerative therapy, neurodegenerative diseases and the idea of using peptides, cytokines, tissue engineering, genetic engineering, advanced stem cell therapy, and polyphenolic phytochemicals to cure damaged tissues and neurodegenerative diseases.

Conventional processes (coagulation, flocculation, sedimentation, and filtration) are widely used in drinking water treatment plants and are considered a good treatment strategy to eliminate cyanobacterial cells and cell-bound cyanotoxins. The diversity of cyanobacteria was investigated using taxonomic cell counts and shotgun metagenomics over two seasons in a drinking water treatment plant before, during, and after the bloom. Changes in the community structure over time at the phylum, genus, and species levels were monitored in samples retrieved from raw water (RW), sludge in the holding tank (ST), and sludge supernatant (SST). Aphanothece clathrata brevis, Microcystis aeruginosa, Dolichospermum spiroides , and Chroococcus minimus were predominant species detected in RW by taxonomic cell counts. Shotgun metagenomics revealed that Proteobacteria was the predominant phylum in RW before and after the cyanobacterial bloom. Taxonomic cell counts and shotgun metagenomic showed that the Dolichospermum bloom occurred inside the plant. Cyanobacteria and Bacteroidetes were the major bacterial phyla during the bloom. Shotgun metagenomics also showed that Synechococcus , Microcystis , and Dolichospermum were the predominant detected cyanobacterial genera in the samples. Conventional treatment removed more than 92% of cyanobacterial cells but led to cell accumulation in the sludge up to 31 times more than in the RW influx. Coagulation/sedimentation selectively removed more than 96% of Microcystis and Dolichospermum . Cyanobacterial community in the sludge varied from raw water to sludge during sludge storage (1-13 days). This variation was due to the selective removal of coagulation/sedimentation as well as the accumulation of captured cells over the period of storage time. However, the prediction of the cyanobacterial community composition in the SST remained a challenge. Among nutrient parameters, orthophosphate availability was related to community profile in RW samples, whereas communities in ST were influenced by total nitrogen, Kjeldahl nitrogen (N- Kjeldahl), total and particulate phosphorous, and total organic carbon (TOC). No trend was observed on the impact of nutrients on SST communities. This study profiled new health-related, environmental, and technical challenges for the production of drinking water due to the complex fate of cyanobacteria in cyanobacteria-laden sludge and supernatant., Competing Interests: The authors declare no conflict of interest.

In this work, a novel molecularly imprinted electrochemical sensor (MIES) has been fabricated based on electropolymerization of a molecularly imprinted polymer (MIP) onto a glassy carbon electrode (GCE) modified with gold-palladium alloy nanoparticles (AuPd NPs)/polydopamine film (PDA)/multiwalled carbon nanotubes-chitosan-ionic liquid (MWCNTs-CS-IL) for voltammetric and impedimetric determination of cholestanol (CHO). Modifications applied to the bare GCE formed an excellent biocompatible composite film which was able to selectively detect CHO molecules. Modifications applied to the bare GCE were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (SEM). Under optimal experimental conditions, the sensor was able to detect CHO in the range of 0.1-60 pM and 1-50 pM by EIS and DPV, respectively. Moreover, the sensor showed high sensitivity, selectivity, repeatability, reproducibility, low interference and good stability towards CHO determination. Our records confirmed that the sensor was successfully able to the analysis real samples for determination of CHO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Polycystic ovary syndrome (PCOS) is one of the prevalent endocrine-metabolic disorders. It is proposed that oxidative stress contributes to PCOS susceptibility and its metabolic associations. The current study aimed to investigate the influence of GPx1 (rs1050450), MnSOD (rs4880), and Catalase (rs1001179) variants with PCOS susceptibility, for the first time., Methods: In a case-control study, 350 Kurdish female volunteers (175 PCOS patients and 175 healthy controls) from Western Iran were studied. Genotyping for GPx1 and MnSOD were done using PCR-RFLP and for CAT the allele-specific PCR method was used., Results: The percentage of patients suffering from hirsutism, acne, and acanthosis among patients with PCOS were 44.6%, 30.3%, and 14.9%, respectively. Distribution of alleles among patients suffering from PCOS versus healthy women was 'Pro' (69.1% vs 68.8%) and 'Leu' (31.4% vs 31.2%) for Gpx1, 'Ala' (61.43% vs 56.57%) and 'Val' (38.57% vs 43.43%) for MnSOD, and 'C' (83.43% vs 84.57%) and 'T' (16.57% vs 15.43%) for CAT., Conclusion: GPx1 (rs1050450), MnSOD (rs4880), and CAT (rs1001179) variants might not be a risk factor for PCOS., (© 2018 Wiley Periodicals, Inc.)

Opioids bind to specific receptors that are located in the central nervous system (CNS) and many other organs such as cardiovascular tissue. Morphine binds to opioid receptors and can induce oxidative stress under some certain conditions. Thymoquinone (TQ) has shown many therapeutic effects such as anti-inflammatory, antioxidant and immunomodulatory ones. Considering the oxidative effects of morphine, antioxidant effects of TQ and effects of oxidative damage in various types of biomolecules, the present study was conducted to determine the effect of morphine plus TQ on the expression of apoptotic genes in the heart of male mice. Hence we used real-time PCR to identify alterations in mRNA expression of genes involved in apoptotic pathway, including p53, Bax and Bcl-2 between the morphine-treated and TQ plus morphine-treated mice. Serum nitric oxide (NO) (Griess assay) and total antioxidant capacity (TAC) were analyzed and compared. In the morphine group, compared to control group, a significant increase in P53 and Bax mRNA expression and a significant decrease in Bcl-2 mRNA expression were observed (p &lt; 0.01). In TQ plus morphine groups, NO was decreased (P &lt;0 .001) and TAC levels were increased significantly (P &lt; .001). Interestingly, TQ (9 and 18 mg/kg) plus morphine caused a significant decrease in p53 and Bax and a significant increase in Bcl2 mRNA expression, compared to morphine-treated group (p &lt; 0.01). Collectively, the results of this study indicated that TQ, as an antioxidant, can improve the apoptotic effects induced by morphine in the heart tissue of mice.

: Human mesenchymal stem cells (hMSCs) are being increasingly pursued as potential therapies for immune-mediated conditions, including multiple sclerosis. Although they can suppress human Th1 responses, they reportedly can reciprocally enhance human Th17 responses. Here, we investigated the mechanisms underlying the capacity of hMSCs to modulate human Th1 and Th17 responses. Human adult bone marrow-derived MSCs were isolated, and their purity and differentiation capacity were confirmed. Human venous peripheral blood mononuclear cells (PBMC) were activated, alone, together with hMSC, or in the presence of hMSC-derived supernatants (sups). Cytokine expression by CD4+ T-cell subsets (intracellular staining by fluorescence-activated cell sorting) and secreted cytokines (enzyme-linked immunosorbent assay) were then quantified. The contribution of prostaglandin E2 (PGE2) as well as of myeloid cells to the hMSC-mediated regulation of T-cell responses was investigated by selective depletion of PGE2 from the hMSC sups (anti-PGE2 beads) and by the selective removal of CD14+ cells from the PBMC (magnetic-activated cell sorting separation). Human MSC-secreted products could reciprocally induce interleukin-17 expression while decreasing interferon-γ expression by human CD4+ T cells, both in coculture and through soluble products. Pre-exposure of hMSCs to IL-1β accentuated their capacity to reciprocally regulate Th1 and Th17 responses. Human MSCs secreted high levels of PGE2, which correlated with their capacity to regulate the T-cell responses. Selective removal of PGE2 from the hMSC supernatants abrogated the impact of hMSC on the T cells. Selective removal of CD14+ cells from the PBMCs also limited the capacity of hMSC-secreted PGE2 to affect T-cell responses. Our discovery of a novel PGE2-dependent and myeloid cell-mediated mechanism by which human MSCs can reciprocally induce human Th17 while suppressing Th1 responses has implications for the use of, as well as monitoring of, MSCs as a potential therapeutic for patients with multiple sclerosis and other immune-mediated diseases., Significance: Although animal studies have generated a growing interest in the anti-inflammatory potential of mesenchymal stem cells (MSCs) for the treatment of autoimmune diseases, MSCs possess the capacity to both limit and promote immune responses. Yet relatively little is known about human-MSC modulation of human disease-implicated T-cell responses, or the mechanisms underlying such modulation. The current study reveals a novel prostaglandin E2-dependent and myeloid cell-mediated mechanism by which human MSCs can reciprocally regulate human Th17 and Th1 responses, with implications for the use of MSCs as a potential therapeutic for patients with multiple sclerosis and other immune-mediated diseases., (©AlphaMed Press.)

Left atrial appendage aneurysms (LAAA) are extremely rare. This condition is usually diagnosed incidentally or after the occurrence of thrombotic events or cardiac tachyarrhythmias in the second to fourth decades of life. It can predispose to hazardous adverse events, including atrial fibrillation, myocardial infarction, and systemic thromboembolism. We report a case of LAAA in a 68-year-old woman presenting with atypical chest pain, exertional dyspnea, and episodes of sudden-onset palpitation. Aneurysmectomy with the patient under cardiac arrest with cardiopulmonary bypass was performed. In addition, we explore the diagnosis, management, and prognosis of this entity through a meticulous literature review., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Congenital lesions of the mitral valve are relatively rare and are associated with a wide spectrum of cardiac malformations. The surgical management of congenital mitral valve malformations has been a great challenge., Objectives: The aim of this study was to evaluate the early and intermediate-term outcome of congenital mitral valve (MV) surgery in children and to identify the predictors for poor postoperative outcomes and death., Patients and Methods: In this retrospective study, 100 consecutive patients with congenital MV disease undergoing mitral valve surgery were reviewed in 60-month follow-up (mean, 42.4 ± 16.4 months) during 2008 - 2013. Twenty-six patients (26%) were under one-year old. The mean age and weight of the patients were 41.63 ± 38.18 months and 11.92 ± 6.12 kg, respectively. The predominant lesion of the mitral valve was MV stenosis (MS group) seen in 21% and MR (MR group) seen in 79% of the patients. All patients underwent preoperative two-dimensional echocardiography and then every six months after surgery., Results: Significant improvement in degree of MR was noted in all patients with MR during postoperative and follow-up period in both patients with or without atrioventricular septal defect (AVSD) (P = 0.045 in patients with AVSD and P = 0.008 in patients without AVSD). Decreasing trend of mean gradient (MG) in MS group was statistically significant (P = 0.005). In patients with MR, the mean pulmonary artery pressure (PAP) had improved postoperatively (P < 0.001). Although PAP in patients with MV stenosis was reduced, this reduction was not statistically significant (P = 0.17). In-hospital mortality was 7%. Multivariate analysis demonstrated that age (P < 0.001), weight (P < 0.001), and pulmonary stenosis (P = 0.03) are strong predictors for mortality. Based on the echocardiography report at the day of discharge from hospital, surgical results were optimal (up to moderate degree for MR group and up to mild degree for MS group) in 85.7% of patients with MS and in 76.6% of patients with MR. Age (P = 0.002) and weight (P = 0.003) of patients are strong predictors for surgical success in multivariate analysis., Conclusions: Surgical repair of the congenital MV disease yields acceptable early and intermediate-term satisfactory valve function and good survival at intermediate-term follow-up. Strong predictors for poor surgical outcome and death were age smaller than 1 year, weight smaller or equal than 6 kg, and associated cardiac anomalies such as pulmonary stenosis.

Background: Tracheal stenosis, which has received more emphasis recently, is a common post intubation complication and may develop due to different reasons. One important reason is the endotracheal tube cuff pressure. Therefore, this study sought to examine the accuracy of diagnostic test for palpation and minimal occlusive volume techniques to measure the endotracheal tube cuff pressure., Materials and Methods: In this cross sectional study, the accuracy of diagnostic tests for palpation and minimal occlusive volume techniques to measure the endotracheal tube cuff pressure was assessed in 101 patients aged over 18 years who had undergone open heart surgery and post-surgical mechanical ventilation in the ICU., Results: In the palpation technique, the cuff pressure of 27 patients (26.7%) was reported to be out of the permissible range and for the rest of them (74 patients, 73.3%) it was within the permissible range. Then, the cuff pressure was checked by the standard method using a manometer and after comparing the results it was found that the cuff pressure of 92 patients (91.1%) was not in the permissible range and only nine patients (8.9%) had a cuff pressure within the permissible range (20-30 cm H2O). In minimal occlusive volume method compared with the standard method, 22 patients (21.7%) had cuff pressure within the permissible range of 20-30 cm H2O, and 79 of them (78.2%) had cuff pressure out of the permissible range and higher than the upper limit., Conclusion: This study recommends that the best way to measure the endotracheal tube cuff pressure is to use a cuff manometer, and when it is not available, the minimal occlusive volume would be a better alternative compared to the palpation technique to keep the cuff pressure within a proper range to avoid tracheotomy complications such as tracheal stenosis.

Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy., Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity., Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort., Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments., (© 2014 American Neurological Association.)

Introduction: Excessive fibrinolysis contributes to post-cardiopulmonary bypass bleeding. Tranexamic Acid (TXA) and Caproamin Fides are synthetic lysine analogues that inhibit plasminogen-fibrin binding. The present study aimed to compare TXA and Caproamin Fides versus placebo in patients undergoing elective coronary artery revascularization., Methods: We analyzed perioperative data of 300 adult patients undergoing coronary artery revascularization. Patients were randomly allocated to receive TXA (n=100), Caproamin Fides (n=100) or placebo (n=100) during perioperative time. Mediastinal bleeding during the first 24 hours post-operation, transfusion requirement and post-surgical complications were assessed., Results: Most descriptive and intra-operative parameters were well comparable between the 3 study groups. Except for mean number of packed red blood cell (PRBC) units transfused during ICU stay (P=0.01), patients in the Caproamin Fides and TXA groups did not show any statistically significant differences regarding transfusion of blood products during peri-operative period. There was no evidence of a significant difference in mediastinal blood loss during the first 24 hours post-operation between the patients receiving TXA or placebo, while patients in the Caproamin Fides group had significantly lower mediastinal bleeding than the other 2 groups (Caproamin Fides vs. placebo, P=0.002, <0.001 and <0.001 at 6, 12 and 24 hours post-operation; Caproamin Fides vs. TXA, P=0.009, 0.003, <0.001 at 6, 12 and 24 hours post-operation). The incidence of postoperative complications were comparable between Caproamin Fides and TXA groups (P>0.05)., Conclusion: In conclusion, Caproamin Fides seems to be superior to TXA regarding the blood saving effects in patients undergoing coronary artery revascularization.

Objective: To define changes in phenotype and functional responses of reconstituting T cells in patients with aggressive multiple sclerosis (MS) treated with ablative chemotherapy and autologous hematopoietic stem cell transplantation (HSCT)., Methods: Clinical and brain magnetic resonance imaging measures of disease activity were monitored serially in patients participating in the Canadian MS HSCT Study. Reconstitution kinetics of immune-cell subsets were determined by flow cytometry, whereas thymic function was assessed using T-cell receptor excision circle analyses as well as flow cytometry measurements of CD31+ recent thymic emigrants (RTEs). Functional assays were performed to track central nervous system-autoreactive antigen-specific T-cell responses, and the relative capacity to generate Th1, Th17, or Th1/17 T-cell responses., Results: Complete abrogation of new clinical relapses and new focal inflammatory brain lesions throughout the 2 years of immune monitoring following treatment was associated with sustained decrease in naive T cells, in spite of restoration of both thymic function and release of RTEs during reconstitution. Re-emergence as well as in vivo expansion of autoreactive T cells to multiple myelin targets was evident in all patients studied. The reconstituted myelin-specific T cells exhibited the same Th1 and Th2 responses as preablation myelin-reactive T cells. In contrast, the post-therapy T-cell repertoire exhibited a significantly diminished capacity for Th17 responses., Interpretation: Our results indicate that diminished Th17 and Th1/17 responses, rather than Th1 responses, are particularly relevant to the abrogation of new relapsing disease activity observed in this cohort of patients with aggressive MS following chemoablation and HSCT., (Copyright © 2013 American Neurological Association.)

Salinity stress is of great importance in arid and semi-arid areas of the world due to its impact in reducing crop yield. Under salinity stress, the amount of 1-aminocyclopropane-1-carboxylate (ACC), a precursor for ethylene production in plants, increases. Here, we conducted research under the hypothesis that isolated ACC deaminase-producing Pseudomonas fluorescens and Pseudomonas putida can alleviate the stressful effects of salinity on canola (Brassica napus L.) growth. The experiments were conducted in the Soil and Water Research Institute, Tehran, Iran. Seven experimental stages were conducted to isolate and characterize ACC deaminase-producing Pseudomonas fluorescens strains and to determine factors enhancing their growth and, consequently, their effects on the germination of canola seeds. Under salinity stress, in 14% of the isolates, ACC deaminase activity was observed, indicating that they were able to utilize ACC as the sole N-source. Bacterial strains differed in their ability to synthesize auxin and hydrogen cyanide compounds, as well as in their ACC deaminase activity. Under salinity stress, the rate of germinating seeds inoculated with the strains of ACC deaminase-producing Pseudomonas fluorescens and Pseudomonas putida, and seedling growth was significantly higher. These results indicate the significance of soil biological activities, including the activities of plant growth-promoting bacteria, in the alleviation of soil stresses such as salinity on plant growth.

Objectives: To determine (i) whether serum inflammatory markers TNFalpha, IL-1beta. IL-6, and leptin are increased in post-poliomyelitis syndrome (PPS) compared to healthy controls; and (ii) whether an association exists between elevated inflammatory markers and clinical parameters in PPS. The cause of PPS is unknown, but abnormal inflammatory responses have been implicated in several small studies., Methods: Serum inflammatory markers were measured (by Luminex) in 51 PPS patients and 26 normal controls. Clinical parameters assessed included disease duration, muscle strength (Medical Research Council sumscore), fatigue (Fatigue Severity Scale and Multidimensional Fatigue Inventory), and pain (visual analog scale scores)., Results: In PPS, TNFalpha levels, as well as IL-6 and leptin were significantly increased compared to controls (Wilcoxon rank-sum test, p=0.03 for TNFalpha, p=0.03 for IL-6, p=0.01 for leptin). The elevated TNFalpha levels in PPS were associated with increased pain due to illness (Spearman correlation coefficient r=0.36, 95% C.I. 0.09 to 0.57) and specifically, with muscle pain (r=0.38, 95% C.I. 0.11 to 0.59). There were no correlations between inflammatory markers in PPS and joint pain, muscle strength, fatigue, or disease duration., Conclusions: Serum TNFalpha, IL-6 and leptin levels are abnormally increased in PPS patients. Elevated TNFalpha levels appear to be specifically associated with increased muscle pain.

Objective: To assess safety and immune modulation by BHT-3009, a tolerizing DNA vaccine encoding full-length human myelin basic protein, in patients with multiple sclerosis (MS)., Design: The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving placebo were crossed over into an active arm after treatment unblinding., Setting: The trial was conducted at 4 academic institutions within North America. Patients Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous 2 years., Interventions: BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9 after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg)., Main Outcome Measures: The primary outcome measures were safety and tolerability of BHT-3009. Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI, relapses, and analysis of antigen-specific immune responses., Results: BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon-gamma-producing, myelin-reactive CD4+ T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays. We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone., Conclusion: In patients with MS, BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI.

Glatiramer acetate (GA) therapy of patients with multiple sclerosis (MS) represents a unique setting in which in vivo Th2 deviation of T cells is consistently observed and associated with clinical benefit in a human autoimmune disease. We postulated that APCs are important targets of GA therapy and demonstrate that treatment of MS patients with GA reciprocally regulates the IL-10/IL-12 cytokine network of monocytes in vivo. We further show that Th1- or Th2-polarized GA-reactive T cells isolated from untreated or treated MS patients mediate type 1 and 2 APC differentiation of human monocytes, based on their ability to efficiently induce subsequent Th1 and Th2 deviation of naive T cells, respectively. These observations are extended to human microglia, providing the first demonstration of type 2 differentiation of CNS-derived APCs. Finally, we confirm that the fundamental capacity of polarized T cells to reciprocally modulate APC function is not restricted to GA-reactive T cells, thereby defining a novel and dynamic positive feedback loop between human T cell and APC responses. In the context of MS, we propose that GA therapy results in the generation of type 2 APCs, contributing to Th2 deviation both in the periphery and in the CNS of MS patients. In addition to extending insights into the therapeutic mode of action of GA, our findings revisit the concept of bystander suppression and underscore the potential of APCs as attractive targets for therapeutic immune modulation.

A susceptible strain of Heligmosomoides polygyrus was selected for 15 generations with increasing doses of ivermectin (0-6 mg/kg). A passage strain was developed, parallel with the ivermectin-selected strain, to control for changes due to rapid passage from mouse to mouse. The LD50s of the 8th and 15th generations of the ivermectin-selected strain were 1.5 times that of the susceptible strain. The LD50 of the passage strain at generations 8 and 15 remained similar to that of the susceptible strain. Ivermectin efficacy was lower against the LA stage than against the adult stage in the susceptible strain, the Ivermectin-selected strain and the passage strain at generation 8.