Analytical Validation of Aptamer-Based Serum Vancomycin Monitoring Relative to Automated Immunoassays.

The practice of monitoring therapeutic drug concentrations in patient biofluids can significantly improve clinical outcomes while simultaneously minimizing adverse side effects. A model example of this practice is vancomycin dosing in intensive care units. If dosed correctly, vancomycin can effectively treat methicillin-resistant streptococcus aureus (MRSA) infections. However, it can also induce nephrotoxicity or fail to kill the bacteria if dosed too high or too low, respectively. Although undeniably important to achieve effectiveness, therapeutic drug monitoring remains inconvenient in practice due primarily to the lengthy process of sample collection, transport to a centralized facility, and analysis using costly instrumentation. Adding to this workflow is the possibility of backlogs at centralized clinical laboratories, which is not uncommon and may result in additional delays between biofluid sampling and concentration measurement, which can negatively affect clinical outcomes. Here, we explore the possibility of using point-of-care electrochemical aptamer-based (E-AB) sensors to minimize the time delay between biofluid sampling and drug measurement. Specifically, we conducted a clinical agreement study comparing the measurement outcomes of E-AB sensors to the benchmark automated competitive immunoassays for vancomycin monitoring in serum. Our results demonstrate that E-ABs are selective for free vancomycin─the active form of the drug, over total vancomycin. In contrast, competitive immunoassays measure total vancomycin, including both protein-bound and free drug. Accounting for these differences in a pilot study consisting of 85 clinical samples, we demonstrate that the E-AB vancomycin measurement achieved a 95% positive correlation rate with the benchmark immunoassays. Therefore, we conclude that E-AB sensors could provide clinically useful stratification of patient samples at trough sampling to guide effective vancomycin dose recommendations.

Novel and emerging concepts in the role of steroids in thyroid cancer promotion and progression.

Thyroid cancer (TC) is becoming more common all over the world. It is, however, frequently neglected from a scientific standpoint, as they rarely result in a fatal conclusion. The female gender is disproportionately affected, with a frequency of 3 to 5 times higher depending on the severity of the condition, which may or may not cause severe physical discomfort but has a significant influence on life quality. The breakdown of equilibrium between the multiple components that maintain cellular homeostasis may be the cause of the illnesses. On the contrary, excessive or uncontrolled exposure to different hormones, particularly steroids, has been shown to impact the development of thyroid illnesses. The goal of this review is to look at the function of steroids in the expansion and progression of thyroid malignancy (Ref. 54). Keywords: thyroid cancer, signaling, steroid hormone.

Shear Bond Strength of Orthodontic Brackets Bonded with a Self-Adhering Composite in Dry and Saliva-Contaminated Conditions.

OBJECTIVES: The purpose of this study was to evaluate the effect of saliva contamination on shear bond strength (SBS) of orthodontic brackets bonded by a self-adhering composite compared with a conventional adhesive. MATERIALS AND METHODS: This in vitro, experimental study investigated 40 human premolars. The teeth were randomly divided into four groups based on the adhesive type and bonding condition: (I) Vertise Flow composite without saliva contamination (VF), (II) Vertise Flow composite with saliva contamination (VF/S), (III) Transbond XT composite without saliva contamination (TXT), and (IV) Transbond XT composite with saliva contamination (TXT/S). After the preparation step, brackets were bonded to the buccal surface of the teeth, and samples were mounted in acrylic blocks, incubated at 37°C for 24 hours, and underwent thermocycling between 5- 55°C. Next, the SBS was measured by a universal testing machine. Data were analyzed by ANOVA and Tukey's test. P<0.05 was considered statistically significant. RESULTS: ANOVA showed a significant difference in SBS among the groups (P<0.001). The highest SBS was achieved in the TXT group (26.63±9.09 MPa), followed by TXT/S (13.69±4.23 MPa), VF/S (3.68±1.49 MPa), and VF (3.04±1.73 MPa). CONCLUSION: Saliva contamination did not have a significant effect on SBS of brackets bonded with Vertise Flow. However, it did not provide acceptable bond strength for orthodontic bracket bonding in the clinical setting.

The regulatory role of autophagy-related miRNAs in lung cancer drug resistance.

Autophagy is conserved cellular machinery that degrades un-usable proteins and cellular components and has a crucial role in the pathogenesis and drug resistance of various diseases such as lung cancer (LC). Multiple types of endogenous molecules (i.e. miRNAs) have been found to regulate multiple biological processes, such as autophagy. Dysfunction of these molecules is associated with the onset and progression of a variety of human malignancies. Several studies had shown that some miRNAs could mediate autophagy activity in LC cells, which would affect drug resistance as a major problem in LC therapy. Therefore, identifying the underlying molecular targets of miRNAs and their function in autophagy pathways could develop new treatment interventions for LC patients. In this review, we will summarize the interplay between miRNAs, autophagy, and drug resistance of LC patients, as well as the genes and molecular pathways that are involved.

The expression pattern of VISTA in the PBMCs of relapsing-remitting multiple sclerosis patients: A single-cell RNA sequencing-based study.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Dysregulated immune responses have been implicated in MS development. Growing evidence has indicated that inhibitory immune checkpoint molecules can substantially regulate immune responses and maintain immune tolerance. V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule that can suppress immune responses; however, its expression pattern in the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) has not thoroughly been studied. Herein, we evaluated Vsir expression in PBMCs of RRMS patients and characterized the expression pattern of the Vsir in the PBMCs of MS patients. Besides, we investigated the effect of fingolimod, IFNß-1α, glatiramer acetate (GA), and dimethyl fumarate (DMF) on Vsir expression in PBMCs of RRMS patients. Our results have shown that Vsir expression is significantly downregulated in the PBMCs of patients with RRMS. Besides, the single-cell RNA sequencing results have demonstrated that Vsir expression is downregulated in classical monocyte, intermediate monocytes, non-classical monocytes, myeloid DCs (mDC), Plasmacytoid dendritic cells (pDCs), and naive B-cells of PBMCs of MS patients compared to the control. In addition, DMF, IFNß-1α, and GA have significantly upregulated Vsir expression in the PBMCs of RRMS patients. Collectively, the current study has shed light on Vsir expression in the PBMCs of MS patients; however, further studies are needed to elucidate the significance of VISTA in the mentioned immune cells.

Evaluating the HLA-G (rs1063320) genetic variant and risk of human papillomavirus infection: a meta-analysis of 953 cases and 877 controls.

Human leukocyte antigen-G (HLA-G) has immune-modulatory functions. Although the role of genetic variant HLA-G (rs1063320) in susceptibility to human papillomavirus (HPV) infection has been widely considered, it is still a matter of discussion. In order to shed light on the issue, we, therefore, conducted a meta-analysis to evaluate the common impact of the HLA-G (rs1063320) variant on susceptibility to HPV infection. Subsequently, the distribution of genotypes, genotyping techniques and ethnicity groups was collected, and general analyses were performed. A total number of five studies with 953 cases and 877 controls were found to meet our criteria. The polymorphism of HLA-G (rs1063320) was evaluated. This is the first meta-analysis to explore the connection between the HLA-G 3' UTR + 3142C/G (rs1063320) genetic variant and the risk of HPV infection. Our results showed no association between the variant of HLA-G 3' UTR + 3142C/G (rs1063320) and susceptibility to HPV infection in studied target populations.Impact StatementWhat is already known on this subject? Human papillomavirus (HPV) is the most widespread sexually transmitted infection in both men and women all over the world. It is correlated with prominent load of diseases and malignancies, including anogenital warts and anogenital and oropharyngeal cancers. In recent years, several studies manifested that different SNPs located on special genes seems to influence HPV infection risk.What the results of this study add? Our findings disclosed no relation between the variant of HLA-G 3' UTR + 3142C/G (rs1063320) and vulnerability to HPV infection in the target individuals.What are the implications of these findings for clinical practice and/or further research? The findings in current survey may offer a basis for further study on HLA-G variant in future investigation.

The Effect of Personality Traits on Cognitive Behavioral Therapy Outcomes in Student Pharmacists with Rat Phobia: A Randomized Clinical Trial.

Background: Little is known about which personality traits determine the effectiveness of various types of cognitive-behavioral therapy (CBT) on animal phobia. The objective of the present study was to investigate a possible association between personality traits and the outcome of single- and multi-session CBT. Methods: The present randomized clinical trial was conducted from November 2018 to May 2019 in Shiraz, Iran. Forty female students with rat phobia, who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria, were systematically allocated into a single- and a multi-session therapy group (odd numbers one-session treatment, even numbers multi-session treatment). In both groups, the students were gradually exposed to rats as part of the treatment. Psychological measures (state-anxiety, rat phobia, and disgust questionnaires) were used to compare pre- and post-intervention outcomes. Multivariate analysis of covariance was used to assess which personality traits influenced the intervention outcome. The statistical analysis was performed using SPSS (version 20.0) and P values<0.05 were considered statistically significant. Results: Rat phobia was positively and significantly affected by conscientiousness (P=0.001) and agreeableness (P=0.003). Of these personality traits, only a higher degree of conscientiousness resulted in a further reduction of state anxiety after the intervention (P=0.005). There were no significant differences between the pre- and post-intervention outcomes. Conclusion: The outcome of single- and multi-session rat phobia therapies was associated with specific personality traits of the participants, namely conscientiousness and agreeableness. Both intervention methods had an equal effect on reducing rat phobia.

The Polymorphism of miR-146a (rs2910164) and Breast Cancer Risk: A Meta-Analysis of 17 Studies.

BACKGROUND: Single-Nucleotide Polymorphisms (SNPs) in genes responsible for coding microRNAs (miRNAs) are shown to be crucial in progression of Breast Cancer (BC). OBJECTIVE: The purpose of this meta-analysis is to obtain more definitive and reliable results due to the ambiguity and inconsistency of the previous findings in this regard. This study aimed at clarifying the association of mir14a polymorphisms with breast cancer. METHODS: We searched PubMed, EMBASE, Web of Science and Google Scholar databases for papers published before August 10, 2019. Afterward, genotypes' distribution, genotyping methods and ethnicity groups were extracted and Overall analyses were conducted. A total number of seventeen researches on 7676 subjects and 7476 controls were found to meet our criteria in this meta-analysis. RESULTS: Our observations confirmed the increased risk in breast cancer with rs 2910164 polymorphism in three genetic models: allele contrast fixed genetic model, Recessive fixed genetic model and CC vs. GG genetic model (P value 0.0109, 0.0404 and 0.0019, respectively). CONCLUSION: The rs2910164 polymorphism is associated with increased breast cancer risk. We suggest that more multicenter studies with larger samples investigate this matter to further clarify the association and verify our findings.

Anti-Breast Cancer Activities of 8-Hydroxydaidzein by Targeting Breast Cancer Stem-Like Cells.

PURPOSE: Cancer stem cells (CSCs) play an important role in various stages of cancer development and therapy refractoriness. 8-Hydroxydaidzein (8-OHD) has revealed anti-cancer activity in different tumors. Accordingly, we aimed to assess the effects of 8-OHD on the suppression of breast cancer stem-like cells (BCSCs). METHODS: The anti-proliferative and pro-apoptotic properties of 8-OHD were examined by MTS assay and flowcytometry. The expression levels of stemness markers and JAK2/STAT proteins were measured by quantitative real time-PCR (qRT-PCR) and western blotting, respectively. RESULTS: 8-OHD significantly decreased three out of six stemness markers and remarkably reduced viability and induced apoptosis of spheroidal and parental cells compared to controls. Further experiments using CD95L, as a death ligand, and ZB4 antibody, as an extrinsic apoptotic pathway blocker, showed that 8-OHD induced apoptosis through the intrinsic pathway, proposing a mechanism by which 8-OHD triggers apoptosis. Results of western blot analysis also revealed a marked decline in the phosphorylation of JAK2 and STAT proteins. CONCLUSION: Our study, for the first time, elucidated an anti-BCSC activity for 8-OHD via decreasing stemness markers, inducing toxicity and stimulating apoptosis in these cells and parental cells. Our results also suggested a novel mechanism by which 8-OHD induces apoptosis in BCSCs.

Therapeutic effects of simultaneous Photobiomodulation therapy (PBMT) and Meloxicam administration on experimental acute spinal cord injury: Rat animal model.

STUDY DESIGN: Application of Photobiomodulation therapy (PBMT) and meloxicam in acute spinal cord injury, functional recovery and histological evaluation. OBJECTIVE: Evaluation of the effect of simultaneous PBMT and meloxicam on treatment of acute experimental spinal cord injury and comparing it with the effect of application of each of them separately. SETTING: The study was conducted at the Department of Surgery & Radiology, Faculty of Veterinary Medicine and Institute of Biomedical Research, University of Tehran, Tehran, Iran. METHODS: Twenty four rats were used in this study. A compression injury was induced to the T8-T9 segment of the spinal cord of rats using a Fogarty embolectomy catheter. Rats were randomly divided into 4 groups including: Control group, PBMT (810 nm-200 mw-8 s-2 weeks) group, Meloxicam (1 mg/kg) group, and PBMT and Meloxicam (mixed) group. After inducing injury, hind limb performance of the rats was evaluated, using BBB test and then treatment intervention was performed and continued for 2 weeks. RESULTS: Four  weeks after injury induction, BBB test results were significantly higher in all treatment groups in comparison to control group, however, there were no significant differences among the treatment groups. In addition, histological findings revealed no significant difference between all 4 study groups. CONCLUSION: According to the results of this study we can conclude that simultaneous and separate application of PBMT and Meloxicam play an effective role in treatment of acute spinal cord injuries.

Association between apolipoprotein E polymorphism and nephropathy in Iranian diabetic patients.

Approximately one-third of diabetic patients develop evidence of nephropathy. Pathogenesis of diabetic nephropathy (DN) remains unclear; however, some genetic and metabolic risk factors have been determined for the development and progression of DN. In the recent genetic studies, polymorphism of apolipoprotein E (ApoE) gene has been reported as a risk factor for the development of DN; however, the results are inconsistent. The aim of the present study was to evaluate the association between ApoE polymorphism and nephropathy in Iranian patient with type 2 diabetes. A total of 197 patients with type 2 diabetes in two groups with and without nephropathy (n = 99 and n = 98, respectively) participated in this case-control study. ApoE genotype was determined by restriction fragment length polymorphism analysis. Biochemical factors of all patients were measured. The frequency of Apo ε4 allele was significantly (P <0.05) lower in DN patients (10.6%) than in diabetic patients without nephropathy (20.4%). No significant difference was observed between the groups regarding Apo ε2 and Apo ε3 allele frequencies. Serum level of total and low-density lipoprotein cholesterol in Apo ε2 carriers was lower than Apo ε3 and Apo ε4 carriers, but this difference was not statistically significant. Frequency of Apo ε4 allele is higher in diabetic patients without nephropathy than DN participants. Given to the result, it seems that Apo ε4 has a protective effect in diabetic patients against nephropathy.