The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP

BORIS expression in ovarian cancer precursor cells alters the CTCF cistrome and enhances invasiveness through GALNT14

High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy

Parenteral provision of micronutrients to pediatric patients: an international expert consensus paper

© 2020 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1002/jpen.1990INTRODUCTION:Micronutrients (vitamins and trace elements) are essential to all nutrition. For children and neonates who are dependent upon nutrition support therapies for growth and development, the prescribed regimen must supply all essential components. This paper aims to facilitate interpretation of existing clinical guidelines into practical approaches for the provision of micronutrients in pediatric parenteral nutrition. METHODS:An international, interdisciplinary expert panel was convened to review recent evidence-based guidelines and published literature to develop consensus- based recommendation on practical micronutrient provision in pediatric parenteral nutrition. RESULTS:The guidelines and evidence have been interpreted as answers to 10 commonly asked questions around the practical principles for provision and monitoring of micronutrients in pediatric patients CONCLUSION: Micronutrients are an essential part of all parenteral nutrition and should be included in the pediatric nutrition therapy care plan.Published versio

Effect of nocturnal hypoxemia on glycemic control among diabetic Saudi patients presenting with obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) is a prevalent disease that is associated with an increased incidence of type II diabetes mellitus (DM) if left untreated. We aimed to determine the association between glycosylated hemoglobin (HbA1c) levels and both nocturnal hypoxemia and apnea-hypopnea index (AHI) among a Saudi patients with OSA.MethodsA cross-sectional study that enrolled 103 adult patients diagnosed with DM and confirmed to have OSA by full night attended polysomnography between 2018 and 2021. Those who presented with acute illness, chronic obstructive pulmonary disease (COPD)/restrictive lung diseases causing sleep-related hypoxemia, or no available HbA1c level within 6 months before polysomnography were excluded from the study. Univariate and multivariate linear regression analyses between HbA1c levels and parameters of interest were tested.ResultsSixty-seven (65%) of the studied population had uncontrolled DM (HbA1c ≥7%). In univariate regression analysis, there was a significant positive association between HbA1c, and sleep time spent with an oxygen saturation below 90% (T90), female gender, and body mass index (BMI) (p<0.05) but not AHI, or associated comorbidities (p>0.05). In the multivariate analysis, HbA1c was positively associated with increasing T90 (p<0.05), and ODI (p<0.05), but not with AHI (p>0.05).ConclusionNocturnal hypoxemia could be an important factor affecting glycemic control in patients with OSA suffering from DM irrespective of the severity of both diseases

Construct validity, test–retest reliability, and responsiveness of the Arabic version of the upper limb functional index

Abstract Background The upper limb functional index (ULFI) is a widely used self-report outcome measure questionnaire with robust psychometric properties to assess the upper limb musculoskeletal disorders (UL-MSDs). This study aimed to investigate the psychometric properties of the Arabic version of ULFI (ULFI-Ar). Methods In this observational study, 139 patients (87 male, 52 females with mean age of 38.67 ± 13.04 year) with various UL-MSD’s, completed the ULFI-Ar, Disability of Arm, Shoulder, and Hand questionnaire (DASH-Arabic), and numeric pain rating scale (NPRS-Arabic). All participants determined the factor structure, and the construct validity. A subgroup of the participants determined test–retest reliability (n = 46) and responsiveness (n = 27). Results The ULFI-Ar construct validity obtained by the expletory factor analysis as one-factor structure, demonstrated an excellent test–retest reliability [intraclass correlation coefficient (ICC2:1) = 0.95], measurement error [standard error of measurement (SEM) = 4.43%; minimal detectable change at 90% confidence interval (MDC90) = 10.34%], medium internal responsiveness [Cohen’s d = 0.62 and standard response of mean (SRM) = 0.67], strong external responsiveness DASH-Arabic (r =—0.90; p < 0.001), and negative strong correlation with NPRS-Arabic (r =—0.75, p < 0.001). Conclusions The ULFI-Ar is a valid, reliable, and responsive self-report questionnaire to assess UL-MSDs in Arabic speaking patients

Total Salivary Fluoride Concentrations of Healthy Adult Subjects Following Toothbrushing with Different Formulations of Fluoridated Toothpastes With and Without Post-brushing Water Rinsing A Double Blinded Randomised Controlled Trial

Background: Caries prevalence has declined significantly since the introduction of fluoridated toothpastes. There have been a number of developments with regards to specific active fluoride ingredients but not enough evidence to support one over the other. Aim: To compare the salivary fluoride concentrations of different fluoride formulations in the form of toothpaste: fluoride-free (0 ppmF), sodium fluoride (1,450 ppmF), sodium monofluorophosphate (1,450 ppmF), sodium fluoride and monofluorophosphate combined (1,450 ppmF), stannous fluoride and sodium fluoride combined (1,450 ppmF) and amine fluoride (1,400 ppmF) with and without post-brushing water rinsing. Design: Study registered with ClilincalTrials.gov public database (NCT02740803). In vivo double-blinded randomised controlled trial measuring salivary fluoride concentrations following brushing with six toothpaste formulations. Power calculation was performed using PASS11.0 software and the total sample size of 120 was recruited in this study. Participants brushed with 1.0g of one of six different formulations of toothpastes either with or without water rinsing post-brushing. Participants were randomly assigned to groups using an online random team generator. Saliva was collected at six different times (baseline and at 1, 15, 30, 60 and 90 minute(s) post-brushing]. Samples were analysed using a fluoride ion-specific sensitive electrode connected to an ion analyser. Codes were broken after data analysis. Data analysis was performed using IBM SPSS 23 software. Results: Demographic characteristics were not significant variables (p>0.05). Time, toothpaste formulation and rinsing methods had significant effects (p<0.05). In general, amine fluoride toothpaste resulted in significantly higher salivary fluoride concentrations at 90 minutes than control groups, in both rinsing and non-rinsing groups. Sodium monofuorophosphate toothpaste did not result in significant difference compared to control group at any time point, in both rinsing and non-rinsing groups. Conclusion: The results of this study supports the current recommendation of no rinsing post-brushing. It also supports the previous literature in that amine fluoride resulted in significantly higher fluoride concentrations

Iso-Trapping Measurement Technique for Characterization of Self-Heating in a GaN HEMT

The temperature response of field-effect transistors (FETs) to instantaneous power dissipation has been shown to be significant at high frequencies, even though the self-heating process has a very slow time constant. This affects intermodulation at high frequencies. A major difficulty in characterizing the self-heating process in microwave FETs is to differentiate between the self-heating and charge-trapping rates. An iso-trapping measurement technique is proposed by which it becomes possible to characterize the self-heating process in an FET in isolation from the effect of the charge-trapping process in the FET. The results of iso-trapping measurements performed on a GaN high-electron-mobility transistor are presented, and used to successfully characterize the self-heating process