Exploring the potential of predicted miRNAs on the genes involved in the expansion of hematopoietic stem cells.

A major challenge in therapeutic approaches applying hematopoietic stem cells (HSCs) is the cell quantity. The primary objective of this study was to predict the miRNAs and anti-miRNAs using bioinformatics tools and investigate their effects on the expression levels of key genes predicted in the improvement of proliferation, and the inhibition of differentiation in HSCs isolated from Human umbilical cord blood (HUCB). A network including genes related to the differentiation and proliferation stages of HSCs was constructed by enriching data of text (PubMed) and StemChecker server with KEGG signaling pathways, and was improved using GEO datasets. Bioinformatics tools predicted a profile from miRNAs containing miR-20a-5p, miR-423-5p, and chimeric anti-miRNA constructed from 5'-miR-340/3'-miR-524 for the high-score genes (RB1, SMAD4, STAT1, CALML4, GNG13, and CDKN1A/CDKN1B genes) in the network. The miRNAs and anti-miRNA were transferred into HSCs using polyethylenimine (PEI). The gene expression levels were estimated using the RT-qPCR technique in the PEI + (miRNA/anti-miRNA)-contained cell groups (n = 6). Furthermore, CD markers (90, 16, and 45) were evaluated using flow cytometry. Strong relationships were found between the high-score genes, miRNAs, and chimeric anti-miRNA. The RB1, SMAD4, and STAT1 gene expression levels were decreased by miR-20a-5p (P < 0.05). Additionally, the anti-miRNA increased the gene expression level of GNG13 (P < 0.05), whereas the miR-423-5p decreased the CDKN1A gene expression level (P < 0.01). The cellular count also increased significantly (P < 0.05) but the CD45 differentiation marker did not change in the cell groups. The study revealed the predicted miRNA/anti-miRNA profile expands HSCs isolated from HUCB. While miR-20a-5p suppressed the RB1, SMAD4, and STAT1 genes involved in cellular differentiation, the anti-miRNA promoted the GNG13 gene related to the proliferation process. Notably, the mixed miRNA/anti-miRNA group exhibited the highest cellular expansion. This approach could hold promise for enhancing the cell quantity in HSC therapy.

Saturated fatty acids inhibit unsaturated fatty acid induced glucose uptake involving GLUT10 and aerobic glycolysis in bovine granulosa cells.

Fatty acids have been shown to modulate glucose metabolism in vitro and in vivo. However, there is still a need for substantial evidence and mechanistic understanding in many cell types whether both saturated and unsaturated fatty acids (SFAs and UFAs) pose a similar effect and, if not, what determines the net effect of fatty acid mixes on glucose metabolism. In the present study, we asked these questions by treating granulosa cells (GCs) with the most abundant non-esterified fatty acid species in bovine follicular fluid. Results revealed that oleic and alpha-linolenic acids (UFAs) significantly increased glucose consumption compared to palmitic and stearic acids (SFAs). A significant increase in lactate production, extracellular acidification rate, and decreased mitochondrial activity indicate glucose channeling through aerobic glycolysis in UFA treated GCs. We show that insulin independent glucose transporter GLUT10 is essential for UFA driven glucose consumption, and the induction of AKT and ERK signaling pathways necessary for GLUT10 expression. To mimic the physiological conditions, we co-treated GCs with mixes of SFAs and UFAs. Interestingly, co-treatments abolished the UFA induced glucose uptake and metabolism by inhibiting AKT and ERK phosphorylation and GLUT10 expression. These data suggest that the net effect of fatty acid induced glucose uptake in GCs is determined by SFAs under physiological conditions.

Effects of Bacillus in Pectobacterium quorum quenching: A survey of two different acyl-homoserine lactonases.

Numerous functions in pathogenic Pectobacterium are regulated by quorum sensing (QS). Two different aiiA genes isolated from Bacillus sp. A24(aiiAA24) and Bacillus sp. DMS133(aiiADMS133) were used. Both genes encode acyl-homoserine lactonase (AiiA), which disrupts QS in Pectobacterium. To investigate the effect of different AiiAs on the inhibition of Pectobacterium carotovorum pathogenicity, two aiiA genes from different Bacillus strains were cloned and the resulting plasmids pME6863 (aiiAA24) and pME7080 (aiiADMS133) were transformed into P. carotovorum EMPCC cells. The effects of different lactonases on virulence features such as enzymatic activity, twitching and swimming motilities, and production of pellicle and biofilm formation were investigated. In EMPCC/pME6863, twitching and swimming motilities, and pellicle production were significantly reduced compared with EMPCC/pME7080. Quantitative real-time PCR (qRT-PCR) was used to measure virulence gene expression in transformed cells compared with expression levels in wild-type EMPCC. The expression of peh and hrpL genes was greatly reduced in EMPCC/pME6863 compared with EMPCC/pME7080. The sequence alignment and molecular dynamic modeling of two different AiiAA24 and AiiADMS133 proteins suggested that the replacement of proline 210 from AiiAA24 to serine in AiiADMS133 caused the reduction of enzyme activity in AiiADMS133.

Prevalence and incidence of multiple sclerosis in Isfahan, Iran between 1996 and 2021: A population-based study.

BACKGROUND: There has been no recent comprehensive epidemiological study on a large and stable population of multiple sclerosis (MS) in Isfahan. Therefore, we conducted this study to estimate the incidence and prevalence of MS in Isfahan province from 1996 to 2021. METHOD: In this population-based study, we utilized the dataset from the Vice-Chancellor's Office of Isfahan University of Medical Sciences, which registers all people diagnosed with MS (PDWM) in Isfahan province, excluding those residing in Kashan city. We measured crude incidence and prevalence of MS, separated by sex, and based on age of MS onset, as well as changes in age of MS onset during observation. RESULTS: A total of 9,909 PDWM were included in our study. The incidence during the time period of 1996-2000 was 5.4/100,000 (1.1/100,000 per year), which subsequently increased to 14.1 (2.8/100,000 per years) and 31.1 per 100,000 (6.2/100,000 per year) during 2001-2005 and 2006-2010, respectively. There was a further increase to 70.9/100,000 (14.2/100,000 per year) in 2011-2015, but it remained stable at 71.8/100,000 (12/100,000 per year) during the period of 2016-2021. In 2016, the age-standardized incidence rates of pediatric-onset, adult-onset, and late-onset MS were 1.8/100,000, 31.4/100,000, and 17.5/100,000, respectively. The prevalence of MS in 2021 was 183.9/100,000. The female/male new case ratio was 4.5 during 1996-2000, decreasing to 4.0, 3.9, 3.9, and 2.9 in the subsequent four five-year periods. The mean age of RRMS onset was 26.3 ± 8.1 between 1990 and 1999, 28.5 ± 8.3 during 2000-2009, and increased to 32.8 ± 9.6 in 2010-2019. CONCLUSION: This study shows that Isfahan has one of the highest incidence rate and prevalence ratio of MS in the region. We observed an increase in the incidence rate during the first decade, followed by stability in the last two five- and six-year periods. Further studies are needed to identify the reasons behind the change in incidence of MS in Iran.

Identification of Key Genes in Angiogenesis of Breast and Prostate Cancers in the Context of Different Cell Types.

INTRODUCTION: Angiogenesis involves the development of new blood vessels. Biochemical signals start this process in the body, which is followed by migration, growth, and differentiation of endothelial cells that line the inside wall of blood vessels. This process is vital for the growth of cancer cells and tumors. MATERIALS AND METHODS: We started our analysis by composing a list of genes that have a validated impact in humans with respect to angiogenesis-related phenotypes. Here, we have investigated the expression patterns of angiogenesis-related genes in the context of previously published single-cell RNA-Seq data from prostate and breast cancer samples. RESULTS: Using a protein-protein interaction network, we showed how different modules of angiogenesis-related genes are overexpressed in different cell types. In our results, genes, such as ACKR1, AQP1, and EGR1, showed a strong cell type-dependent overexpression pattern in the two investigated cancer types, which can potentially be helpful in the diagnosis and follow-up of patients with prostate and breast cancer. CONCLUSION: Our work demonstrates how different biological processes in distinct cell types contribute to the angiogenesis process, which can provide clues regarding the potential application of targeted inhibition of the angiogenesis process.

Evaluation of the impact of polypeptide-p on diabetic rats upon its cloning, expression, and secretion in Saccharomyces boulardii.

This study was designed to evaluate the effectiveness of recombinant polypeptide-p derived from Momordica charantia on diabetic rats. In this research, the optimized sequence of polypeptide-p gene fused to a secretion signal tag was cloned into the expression vector and transformed into probiotic Saccharomyces boulardii. The production of recombinant secretion protein was verified by western blotting, HPLC, and mass spectrometry. To assay recombinant yeast bioactivity in the gut, diabetic rats were orally fed wild-type and recombinant S. boulardii, in short SB and rSB, respectively, at two low and high doses as well as glibenclamide as a reference drug. In untreated diabetic and treated diabetic + SB rats (low and high doses), the blood glucose increased from 461, 481, and 455 (mg/dl), respectively, to higher than 600 mg/dl on the 21st day. Whereas glibenclamide and rSB treatments showed a significant reduction in the blood glucose level. The result of this study promised a safe plant-source supplement for diabetes through probiotic orchestration.

An update on the potential mechanism of gallic acid as an antibacterial and anticancer agent.

Drug resistance to antibacterial and anticancer drugs is one of the most important global problems in the treatment field that is constantly expanding and hinders the recovery and survival of patients. Therefore, it is necessary to identify compounds that have antibacterial and anticancer properties or increase the effectiveness of existing drugs. One of these approaches is using natural compounds that have few side effects and are effective. Gallic acid (GA) has been identified as one of the most important plant polyphenols that health-promoting effects in various aspects such as bacterial and viral infections, cancer, inflammatory, neuropsychological, gastrointestinal, and metabolic disease. Various studies have shown that GA inhibits bacterial growth by altering membrane structure, and bacterial metabolism, and inhibits biofilm formation. Also, GA inhibits cancer cell growth by targeting different signaling pathways in apoptosis, increasing reactive oxygen species (ROS) production, targeting the cell cycle, and inhibiting oncogenes and matrix metalloproteinases (MMPs) expression. Due to the powerful function of GA against bacteria and cancer cells. In this review, we describe the latest findings in the field of the sources and chemical properties of GA, its pharmacological properties and bioavailability, the antibacterial and anticancer activities of GA, and its derivatives alone, in combination with other drugs and in the form of nanoformulation. This review can be a comprehensive perspective for scientists to use medicinal compounds containing GA in future research and expand its clinical applications.

Multiple sclerosis is associated with worse COVID-19 outcomes compared to the general population: A population-based study.

BACKGROUND: We carried out the current study to compare COVID-19-related hospitalization and mortality rates between people living with multiple sclerosis (PLWMS) and MS-free controls from the Isfahan general population. METHOD: In this retrospective population-based study, we used available data from four datasets of Isfahan University of Medical Sciences from January 1, 2020, to August 22, 2021. Data on all PLWMS, SARS-CoV-2 polymerase chain reaction (PCR) and rapid antigen test, hospitalization, and death were included. We compared the odds of COVID-19-related hospitalization and mortality between PLWMS and the control group before and after adjustment for age and sex. We categorized all people into young (18-49 years) and old age (50-79 years) groups and compared the hospitalization rate between people with and without MS. RESULTS: In total, 829 PLWMS and 2494 MS-free controls with confirmed COVID-19 were included. Hospitalization rates among PLWMS and MS-free controls were 16.2% and 16.5% (crude OR= 0.978, 95%CI: 0.79, 1.21). In the adjusted model, PLWMS with COVID-19 had 56% increased odds of hospitalization (OR=1.56, 95%CI: 1.23, 1.97). During follow-up, there were 11 (1.3%) and 49 (2%) COVID-19-related deaths among PLWMS and MS-free controls, respectively. No significant difference between people with and without MS in COVID-19-related mortality rate was observed (crude OR= 0.678, 95%CI: 0.351, 1.31; adjusted OR=2.013, 95%CI: 0.95, 4.26). We found increased odds of hospitalization in young PLWMS compared to those without MS at the same age (OR=1.699, 95%CI: 1.289, 2.240). But, no difference between older people with and without MS was detected (OR=1.005, 95%CI: 0.662, 1.524). CONCLUSION: This study revealed higher odds of hospitalization and mortality due to COVID-19 among PLWMS in comparison to age- and sex-matched controls from the general population. Nevertheless, it remains unclear whether the elevated odds are directly associated with MS itself or if they are influenced by factors such as rituximab using, comorbidity, and disease severity.

Identification of a Novel ARSA Gene Mutation Through High-Throughput Molecular Diagnosis Method in Two Girls with Late Infantile Metachromatic Leukodystrophy.

Metachromatic leukodystrophy (MLD) is a rare leukoencephalopathy caused by pathogenic mutations in the ARSA gene. It manifests as severe motor symptoms, mental problems, and sometimes, seizures. We aimed to investigate the phenotypic manifestations and genetic causes of MLD in an Iranian family. We present the case of a 3-year-old girl who presented with hypotonia, muscular atrophy, and seizures. Neurological and neuromuscular examinations were performed to evaluate clinical characteristics. Whole exome sequencing (WES) was used to detect disease-causing variants. In silico analysis was performed to predict the pathogenicity of this variant. GROMACS software was utilized for molecular dynamic simulation (MDS). Neurological studies revealed marked slowing of motor conduction velocities and an increased motor unit action potential duration. Brain MRI scan revealed white matter abnormalities. By applying WES, we identified a novel homozygous missense variant (NM_000487.6, c.938G > C, p.R313P) in ARSA. Direct sequencing identified this homozygous variant in her asymptomatic younger sister, whereas both parents carried a heterozygous variant. This mutation has not been reported in genetic databases or in literature. In silico analysis predicted that any variation in this DNA position would cause disease, as it is highly conserved. The c.938G > C variant was classified as a pathogenic variant according to ACMG/AMP guidelines. MDS analysis indicated that c.938G > C had a significant impact on both the structure and stabilization of ARSA, ultimately resulting in impaired protein function. The identification of this variant expands the spectrum of ARSA gene mutations associated with MLD and highlights the importance of genetic testing for the diagnosis of MLD.

Comparison of Dextrose Prolotherapy and Triamcinolone Intraarticular Injection on Pain and Function in Patients with Knee Osteoarthritis - A Randomized Clinical Trial.

Background: The present study was performed to assess the therapeutic effects of combined intra and extraarticular dextrose prolotherapy on knee osteoarthritis and its comparison with intra- articular triamcinolone injection. Methods: In this study, 50 patients suffering from knee osteoarthritis were allocated into two groups as a double-blind randomized clinical trial. The first group received one session of dextrose prolotherapy as one intra-articular injection of 10cc dextrose 16% and periarticular intradermal injections of dextrose 12% at 4 points around the knee (2.5 cc at each point). The second group underwent therapy with one intra-articular injection of triamcinolone (40 mg). Results: Compared to pretreatment, both interventions caused significant improvement in pain (evaluated by VAS) and WOMAC (all its components) in 1 and 3 months postintervention (all with P-value < 0.005). In the first month, pain reduction was significantly better in corticosteroid group (P-Value 0.002 and 0.048 respectively). In third month post intervention, improvements in VAS and WOMAC components were significantly greater in prolotherapy group. Conclusions: Both methods of corticosteroid and dextrose prolotherapy (combined intra and extraarticular technique) are effective on pain and function of patients with knee osteoarthritis. Compared to corticosteroid, prolotherapy method was associated with less pain reduction in short- term, but its effects were more persistent and in midterm examinations (3 months), it was more effective than corticosteroid.

Work-Life Balance and Mental Health Outcomes for Generation Z in Germany.

OBJECTIVE: Mental health can be negatively affected if work and private life demands are not balanced. This study proposes exploring work-life balance (WLB) as a predictor of Generation Z's mental health outcomes. METHODS: A cross-sectional online study was conducted to collect data on mental health outcomes and WLB from a sample of Generation Z (N = 134). Three regression models were calculated to examine the predictive effect of WLB on stress, anxiety, and depressive symptoms. RESULTS: The results show a strong statistically significant association between all three mental health outcomes. The regression model suggests work-life balance as a predictor of stress (ß =.-0.404 P = 0.001, R2 = 0.16) and anxiety (ß = .-256 P = 0.001, R2 = 0.06). CONCLUSION: WLB must be considered a significant factor in mental health problems among Generation Z.

Intravaginal Isoniazid (INH) and Sublingual Misoprostol Versus Sublingual Misoprostol Alone for First-Trimester Induced Abortion: A Randomized Controlled Trial.

Background: This study aimed to compare sublingual misoprostol alone or combined with vaginal Isoniazid (INH) for first-trimester abortion. Methods: In this randomized controlled trial, 80 pregnant women with missed abortion candidates for first-trimester abortion were randomly assigned to two groups. The first group received 800 µg sublingual misoprostol every three hours maximum for three doses and the second group received 1500 mg vaginal INH followed by the same dose of misoprostol. Vaginal sonography was performed after 24 hours on both groups to observe any retained product of conception. In case of no response or incomplete abortion, the second course of misoprostol (with the same dose) was administered. The abortion (complete or incomplete) rate was reported within 48 hours after the first dose of misoprostol. Results: The rate of successful intervention (either complete or incomplete) abortion within 48 hours of misoprostol administration was 75% in both groups and was not significantly different (P value = 1). Also, hospitalization duration, abortion time, total misoprostol dosage, and the rate of side effects were similar in the two groups. Five patients in the misoprostol group and three in the misoprostol plus isoniazid group underwent emergent D&C because of heavy bleeding. Conclusion: A combined regimen of sublingual Misoprostol plus vaginal Isoniazid with the prescribed dosage has similar efficacy to sublingual misoprostol alone in first-trimester abortion.

Implementation Challenges for a Multisite Advance Care Planning Pragmatic Trial: Lessons Learned.

BACKGROUND/PROBLEM: Advance care planning (ACP) pragmatic trials are needed. PROPOSED SOLUTION: We determined key system-level activities to implement ACP interventions for a cluster-randomized pragmatic trial. We identified patients with serious illness from 50 primary care clinics across three University of California health systems using a validated algorithm. If patients lacked documented ACP within the last 3 years, they were eligible for an intervention: (Arm 1) an advance directive (AD); (Arm 2) AD + PREPAREforYourCare.org; (Arm 3) AD + PREPARE + lay health navigator outreach. Triggered by an appointment, we mailed and sent interventions through automated electronic health record (EHR) messaging. We collaborated with patients/caregivers, clinicians, payors, and national/health system leader advisors. We are currently finalizing 24 months follow-up data. OUTCOMES/METHODS: We used the Consolidated Framework for Implementation Research (CFIR) and Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to track secular trends and implementation efforts. KEY MESSAGE/RESULTS: Required multisite, system-level activities: 1) obtaining leadership, legal/privacy, and EHR approvals; 2) standardizing ACP documentation; 3) providing clinician education; 3) validating an automated serious illness identification algorithm; 4) standardizing ACP messaging with input from over 100 key advisors; 5) monitoring secular trends (e.g., COVID); and 6) standardizing ACP workflows (e.g., scanned ADs). Of 8707 patients with serious illness, 6883 were eligible for an intervention. Across all arms, 99% received the mailed intervention, 78.3% had an active patient portal (64.2% opened intervention), and 90.5% of arm three patients (n = 2243) received navigator outreach. LESSONS LEARNED: Implementing a multisite health system-wide ACP program and pragmatic trial, with automated EHR-based cohort identification and intervention delivery, requires a high level of multidisciplinary key advisor engagement, standardization, and monitoring. These activities provide guidance for the implementation of other large-scale, population-based ACP efforts.

Effectiveness of BBIBP-CorV vaccine in preventing SARS-CoV2 infection and severe outcomes in people living with multiple sclerosis: A population-based study.

BACKGROUND: The objective of the present study was to estimate the effectiveness of the BBIBP-CorV vaccine (VE) in preventing SARS-CoV-2 infection, related hospitalization, and death among people living with multiple sclerosis (PLWMS). METHODS: In this population-based retrospective observational study, data on all PLWMS, vaccination, SARS-CoV-2 tests, hospitalization, and deaths were collected in Isfahan, Iran between February 9, 2021, and November 4, 2021. We estimated the hazard ratio between vaccinated (partially and fully) and unvaccinated groups using the Andersen-Gill extension of the Cox proportional hazards model. We also performed Cox proportional hazards analysis to identify risk factors for breakthrough infection and COVID-19-related hospitalization in fully-immunized group. RESULTS: Of the 9869 PLWMS, 1368 were in partially-vaccinated group, 4107 were in the fully-vaccinated group, and 3794 were in the unvaccinated group. In the partially-vaccinated group, the estimated VE against COVID-19 infection was 39.3% (16%, 56.1%), hospitalization was 64.9% (1.3%, 87.5%), and mortality was 92.7% (88.8%, 100%). The respective results for the fully-vaccinated group were 63.9% (56%, 70.3%), 75.7% (57.5%, 86.1%), and 100%. Progressive MS was independently associated with a greater risk of breakthrough infection (HR=1.952, 95%CI: 1.174-3.246, p = 0.010). Older adults (≥50 years vs. 18-49 years, HR=3.115, 95%CI: 1.145-8.470, p = 0.026) and those on rituximab (HR=7.584; 95% CI: 1.864-30.854; p = 0.005) were at an increased risk of COVID-19-related hospitalization. CONCLUSION: This study showed that two doses of the BBIBP-CorV vaccine can effectively prevent COVID-19 infection and hospitalization among PLWMS. Old PLWMS and those who treating with rituximab are at increased risk of hospitalization after receiving two doses of the vaccine.

The success of vaginal birth by use of trans-labial ultrasound plus vaginal examination and vaginal examination only in pregnant women with labor induction: a comparative study.

BACKGROUND: Predicting the success of vaginal delivery is an important issue in preventing adverse maternal and neonatal outcomes. Thus, this study aimed to compare the success rate of vaginal birth by using trans-labial ultrasound and vaginal examination, and vaginal examination only in pregnant women with labor induction. METHODS: This was a comparative study including 392 eligible pregnant women with labor induction attending to a teaching hospital affiliated with Iran University of Medical Sciences from April to October 2018 in Tehran, Iran. Women were randomly assigned to two groups; the trans-labial ultrasound plus vaginal examination (group A), and the vaginal examination only (group B). Women were included in the study if they satisfied the following criteria: singleton pregnancy, 37 to 42 weeks of gestational age, fetal head presentation, a living fetus with no abnormalities, uncomplicated pregnancy, and no previous cesarean section or any uterine surgery. We used a partograph for both groups to assess the fetal head position and the fetal head station. In group 1, the Angle of Progression (AoP) and Rotation Angle (RA) were also assessed. Finally, the success and progression of vaginal delivery in two groups were compared by predicting the duration of delivery and mode of delivery. RESULTS: The findings showed that 8.68% of women in the trans-labial plus vaginal examination group delivered by cesarean section, while 6.13% in the vaginal examination only group delivered by cesarean section (P = 0.55). In women with cesarean section in positive fetal head stations, Angle of Progression (AoP) was significantly decreased ranging from 90 to 135 degrees compared to women who delivered vaginally (135-180 degrees; P <  0.001). In addition, the Rotation Angle (RA) was significantly decreased in women with cesarean section ranging from 0 to 30 degrees compared to women who delivered vaginally (60-90degrees; P <  0.001). Further analysis indicated that a higher risk of cesarean section was associated with vaginal examination only as compared to trans-labial ultrasound plus vaginal examination (HR: 8.65, P <  0.001). CONCLUSION: Angle of Progression (AoP) and Rotation Angle (RA) indexes might be useful parameters to predict labor progression and successful vaginal delivery among women undergoing labor induction.

Telephone Outreach Enhances Recruitment of Underrepresented Seriously Ill Patients for an Advance Care Planning Pragmatic Trial.

BACKGROUND: Patients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals. OBJECTIVE: To assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California. DESIGN: Retrospective cohort study PATIENTS: Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone. MAIN MEASURES: Effect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)). RESULTS: Across the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively). CONCLUSIONS: Phone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.

Comparison of the effect of oral and vaginal misoprostol on labor induction: updating a systematic review and meta-analysis of interventional studies.

OBJECTIVES: This study is aimed to compare the effect of oral misoprostol with vaginal misoprostol to induce labor as a systematic review and meta-analysis. METHODS: Electronic databases including PubMed [Medline], Scopus, Web of science, Embase, Ovid, Cochrane library, and ClinicalTrials.gov were searched using the relevant keywords. All RCTs comparing the effect of oral vs vaginal misoprostol on labor induction were considered. The Cochrane Risk of Bias checklist was used for assessing quality of included RCTs. All statistical analyses were completed using STATA (Version 16) and Revman (Version 5). RESULTS: Thirty-three RCTs with 5162 patients (1560 in oral and 2602 in vaginal groups) were included in this meta-analysis. Labor induction length did differ significantly between the two routes of misoprostol administration [Standardized Mean Difference: 0.40 h, 95% confidence interval (CI) 0.34, 0.46; I2: 66.35%; P = 0.04]. In addition, the risk of neonatal death, tachysystole, uterine hyperstimulation, preeclampsia, non-FHR and abortion was lower in the oral misoprostol group and the risk of hypertonus, PROM, oxytocin need and cesarean fever was higher in this group than the vaginal misoprostol group. CONCLUSIONS: Based on results of this meta-analysis, it can be inferred that currently, clinical specialists can decide to use this drug orally or vaginally on a case-by-case basis, depending on the condition of the pregnant mother and the baby.

Introducing photo-crosslinked bio-nanocomposites based on polyvinylidene fluoride/poly(glycerol azelaic acid)-g-glycidyl methacrylate for bone tissue engineering.

As a glycerol-based polyester, poly(glycerol azelaic acid) (PGAz) has shown great potential for biomedical applications, such as tissue engineering. However, it tends to show low mechanical strength and a relatively fast biodegradation rate, limiting its capability of mimicking and supporting a broad range of hard tissues such as bone. Moreover, the typical thermal curing process of poly(glycerol-co-diacids) is one of their drawbacks. To overcome these limitations, glycidyl methacrylate (GMA) moieties were first grafted on the backbone of PGAz herein to achieve a UV-curable PGAz-g-GMA (PGAG) resin. Then polyvinylidene fluoride (PVDF), nano-hydroxyapatite, and Cloisite Na+ nanoclay were used to fabricate photo-crosslinked PGAG/PVDF nanocomposites with efficient properties to mimic various hard tissues. Our results demonstrated that all nanocomposites possessed a semi-crystalline structure with noticeable PVDF ß-phase fraction. The scaffolds yielded Young's modulus, ultimate tensile strength, and elongation at break of 15-24 MPa, 13-15 MPa, and 50-65%, respectively that could meet the requirements for supporting cancellous bone tissue. The presence of nanofillers improved the hydrophilicity and slightly accelerated the biodegradation rate of the scaffolds. Additionally, it was illustrated that the scaffolds had no noticeable in vitro cytotoxicity, and mouse fibroblast L929 cells and osteoblast MG-63 cells attached to and proliferated on their surface desirably. Our findings indicate that the PGAG/PVDF blend and its nanocomposites could be high-potential candidates for a range of hard tissues, specifically cancellous bones.

Assessing Representativeness of Seriously Ill Patient Survey Responders in a Pragmatic Clinical Trial.

Objective: Pragmatic trials often implement an intervention across a population of patients but require information unavailable at the population level that must be reported by a subset of patients. In this pragmatic clinical trial, we compared characteristics of seriously ill patients with those who completed a survey evaluating advance care planning across 3 academic health systems. Methods: A deliberate process including health system and external stakeholders and patients was used to design materials for and the approach to seriously ill patients. We developed a survey and conducted a multistep process to identify seriously ill primary care patients. We evaluated the relationships of age, gender, race and ethnicity, and vulnerability using the social vulnerability index in this population, and explored the representativeness of survey respondents compared with the underlying seriously ill population in terms of age, race and ethnicity, and vulnerability measured. Results: About 5% (8707 patients) of the primary care population was classified as seriously ill, 5351 were mailed a survey and 1100 provided survey responses. Hispanic and Black patients were younger than White patients, and Black and Hispanic patients were more vulnerable than White and Asian patients and patients of other races. Representativeness was high across age and race and ethnicity, although White and Hispanic patients were more likely to respond than Black and Asian patients and patients of other races. Vulnerability in the surveyed sample was nearly identical to the population. Conclusions: A tailored survey and recruitment strategy yielded a representative sample of seriously ill, largely older, primary care respondents in the context of a pragmatic clinical trial.

Comparison of the outcomes of normal vaginal delivery with and without spinal anesthesia in mothers admitted to the maternity ward of Firoozabadi Hospital.

Introduction and Objective: The study of the methods of controlling labor pain is very important. One of the methods of pain relief is spinal anesthesia. Due to the different opinions about the effects of spinal anesthesia on the delivery process and maternal and fetal consequences, this study aimed to evaluate the effects of spinal anesthesia and compare it with normal vaginal delivery without spinal anesthesia. Methods: In this retrospective cohort study, 120 mothers, who were admitted to the maternity ward of Firoozabadi Hospital for delivery, were examined. The patients who met the inclusion criteria were divided into two groups of 60 people, one group receiving spinal anesthesia and one without spinal anesthesia, and then, were evaluated in terms of clinical variables and complications of the mother and fetus. Data were analyzed using SPSS statistical software. Results: The mean age of the mothers was 26.6 ± 5.9 years. Five mothers (4.2%) who received spinal anesthesia underwent emergency cesarean section and a significant difference was shown between the two groups (P = 0.02). The mean duration of the active phase of labor did not show a statistically significant difference between the two groups (P = 0.2), but the duration of the second phase of labor was significantly longer in the mothers who received spinal anesthesia (P = 0.008). Conclusion: Spinal anesthesia can be used as a low-complication method in vaginal delivery to reduce pain.