Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.

The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.

Use of co-production to explore food insecurity in adults with severe mental illness living in Northern England: a mixed-methods study.

BACKGROUND: People living with severe mental illness experience premature mortality from diet-related preventable illnesses. Yet, little research focuses on food insecurity with adults with severe mental illness. This coproduced study aimed to understand the experiences of adults with severe mental illness and food insecurity and strategies to help. METHODS: Following a pragmatism philosophical foundation, we undertook a mixed-methods study involving a survey (online and paper versions) and one-to-one semi-structured interviews (online and telephone) during March 7 to Dec 16, 2022. We recruited participants via existing severe mental illness service user groups and social media in Northern England. Eligible participants were adults (≥18 years) self-reporting a diagnosis of severe mental illness. Ethics approval was obtained from Teesside University and the Health Research Authority (Reference: 22/NR/0010; IRAS ID: 306281), with informed consent given. The target sample size, accounting for a typical survey response rate for people with severe mental illness of 10-20%, was 135. A target sample of 20 interviews was agreed to capture a range of views. Food insecurity was defined as the lack of financial resources needed to ensure someone has reliable access to enough food to meet their dietary, nutritional, and social needs. It is sometimes called food poverty. Quantitative data were analysed using descriptive statistics and binary logistic regression and qualitative data using thematic analysis. FINDINGS: 135 participants completed the survey (mean age 44·67 years [SD 14·1]). Participants were predominantly male (53%, n=72), white (87%, n=117), and from the Yorkshire region (50%, n=68). Overall, prevalence of food insecurity was 50·4% (n=68). Discussion across 13 interviews found food insecurity being a long-rooted experience, including familial and intergenerational experiences of food insecurity: "I grew up… with this insecurity around food" (P002). Recommendations for tackling food insecurity centred on food banks, increasing accessibility, and reducing stigma: "I would like to get more information on where the centres are..." (P006) and "I was referred to, erm, a foodbank … but it's still the stigma that's attached to it." (P002). INTERPRETATION: We found a higher prevalence of food insecurity in this study than in the general population (being 15%), yet limited research with adults with severe mental illness perpetuates food insecurity intergenerational injustices. Food insecurity should be eliminated. However, in the meanwhile, there should be widespread easy access to food banks offering nutritional foods. Limitations of this research include not reaching target sample size and a lack of ethnic diversity. FUNDING: National Institute of Health and Care Research (NIHR) Research for Patient Benefit.

Measuring the association between the opening of a new multi-national restaurant with young people's eating behaviours.

Out-of-home eating (takeaway, take-out and fast-foods) is associated with intakes of higher energy and fat, and lower intakes of micronutrients, and is associated with excess weight gain. In 2017, a unique opportunity arose to measure the association between the opening of a new multi-national fast-food restaurant (McDonald's) and consumption of fast-food on young people aged 11-16. This study uses a repeated cross-sectional design to explore group level change over time with respect to out-of-home eating behaviours of young people. Two secondary schools in Redcar and Cleveland agreed to participate and facilitated the completion of a questionnaire on their pupils eating behaviours at three timepoints a) prior to the new restaurant opening, b) three months post-opening and c) nine months post opening. Reported frequency of visits to McDonald's showed a statistically significant increase in visits between 3 and 9 months of the restaurant opening. This research asks and explores the question of whether the introduction of a new multi-national fast-food restaurant influences eating habits of young people attending schools near the new outlet.

TLR3 stimulation improves the migratory potency of adipose-derived mesenchymal stem cells through the stress response pathway in the melanoma mouse model.

BACKGROUND: Mesenchymal stem cells (MSCs) are utilized as a carrier of anti-tumor agents in targeted anti-cancer therapy. Despite the improvements in this area, there are still some unsolved issues in determining the appropriate dose, method of administration and biodistribution of MSCs. The current study aimed to determine the influence of toll-like receptor 3 (TLR3) stimulation on the potential of MSCs migration to the neoplasm environment in the mouse melanoma model. METHODS AND RESULTS: Adipose-derived MSCs (ADMSCs) were isolated from the GFP+ transgenic C57BL/6 mouse and treated with different doses (1 µg/ml and 10 µg/ml) of polyinosinic-polycytidylic acid, the related TLR3 agonist, at various time points (1 and 4 h). Following the treatment, the expression of targeted genes such as α4, α5, and ß1 integrins and TGF-ß and IL-10 anti-inflammatory cytokines was determined using real-time PCR. In vivo live imaging evaluated the migration index of the intraperitoneally (IP) injected treated ADMSCs in a lung tumor-bearing mouse (C57BL/6) melanoma model (n = 5). The presented findings demonstrated that TLR3 stimulation enhanced both migration of ADMSCs to the tumor area compared with control group (n = 5) and expression of α4, α5, and ß1 integrins. It was also detected that the engagement of TLR3 resulted in the anti-inflammatory behavior of the cells, which might influence the directed movement of ADMSCs. CONCLUSION: This research identified that TLR3 activation might improve the migration via the stimulation of stress response in the cells and depending on the agonist concentration and time exposure, this activated pathway drives the migratory behavior of MSCs.

Fluoride Exposure in Community Prevention Programmes for Oral Health Using Nail Clippings and Spot Urine Samples: A Systematic Review and Meta-Analysis.

Due to practical difficulties in quantifying fluoride exposure in populations, practical and accurate biomarkers can play a major role in the surveillance of fluoride. Among different fluoride biomarkers, spot urine and nail clippings have gained more attention due to their ease of acquisition. However, there is no robust consensus about the accuracy of these biomarkers for the estimation of fluoride exposure. This systematic review and meta-analysis aimed to synthesise evidence on the association between fluoride exposure and the fluoride concentration of spot urine and nail clippings. This review was conducted and reported using the PRISMA Statement. Nine databases (Medline, CINAHL, Web of Science, Scopus, ScienceDirect, Sage Journals Online, Campbell Collaboration, Cochrane Collaboration, and Embase); search engines (Google and Google Scholar); and grey literature were searched up to September 2022. All screening, data extraction, and quality assessments were conducted in duplicate. All experimental and observational research studies that reported the correlation between fluoride exposure and fluoride concentrations of spot urine and/or nail clippings were included. The Mixed-Methods Appraisal tool was used to assess the methodological quality of the included studies. A random effect meta-analysis was carried out to determine the relationship between fluoride exposure and fluoride concentration of biomarkers (i.e., spot urine and nail clippings). Forty-four studies met the inclusion criteria. A total of 694,578 participants were included in this review. Twenty-five studies were included in the meta-analysis. The primary meta-analysis showed a moderate correlation of 0.674 (95% confidence interval [CI]: 0.623-0.725, n = 25) between fluoride intake and fluoride concentration of spot urine and a strong correlation of 0.938 (95% CI: 0.520-1.355, n = 11) between fluoride intake and the fluoride concentration of nail clippings in all age groups. The findings of secondary meta-analyses showed a strong positive correlation between fluoride intake and fluoride/creatinine ratio of spot urine in children (0.929; 95% CI: 0.502-0.991; n = 2). In conclusion, spot urine and nail clippings have the potential to be employed as non-invasively obtained biomarkers in populations. However, due to the scarcity of high quality, relevant studies, more research is needed to establish the validity of these biomarkers.

Trends in cocirculation of oncogenic HPV genotypes in single and multiple infections among the unvaccinated community.

Cocirculation of multiple human papillomavirus (HPV) infections with low, probably high, and high-risk genotypes are to be associated with various grades of infections and cancer progression. The oncogenic high-risk HPVs are distributed and cocirculated throughout the world. This study was investigated to identify HPV genotypes related to genital disorders in unvaccinated women. The subjects were referred from clinics to a molecular lab for HPV testing in Iran as a low-coverage vaccinated country. HPVs DNAs of cervical scrapping and genital tissue specimens of 1,133 un-vaccinated women were genotyped using an in vitro diagnostic line probe (reverse hybridization) assay. In addition, phylogenetic trees were constructed on 100 MY09/MY11 polymerase chain reaction (PCR) amplicons of common genotypes of HPV L1 gene by Sanger sequencing. The mean age of the population study was 32.7 ± 8.0 and the mean age of HPV-positive cases was 31.6 ± 7.8. HPV DNA was detected in 57.8% (655/1133) of women subjects and 42.2% (478/1133) of cases were undetected. Among 655 HPV-positive cases, 639 subjects (56.4%) were related to defined genotypes and 16 subjects (1.4%) were untypeable. The highest prevalence rate of HPV genotypes was identified in the 25-34 years. The top 6 dominant HPVs in single and multiple genotypes were HPV6 (284/655 [43.4%]), HPV16 (111/655 [16.9%]), HPV31 (72/655 [11%]), HPV53 (67/655 [10.2%]), HPV11 (62/655 [9.5%]), and HPV52 (62/655 [9.5%]). Moreover, single, multiple and untypeable HPV genotypes were diagnosed as follows: 1 type (318/655 [48.5%]), 2 types (162/655 [24.8%]), 3 types (83/655 [12.7%]), 4 types (42/655 [6.5%]), more than 5 types (34/655 [5.3%]), and 1.4% un-typeable subjects. The sequenced partial L1 gene of HPV genotypes (GenBank databases under the accession numbers: MH253467-MH253566) confirmed and determined the cocirculated HPV genotypes' origins and addressed helpful insights into the future viral epidemiology investigations. Multiple HPV infections and cocirculation of various oncogenic HPV genotypes among the normal population (women and men) with asymptomatic forms are still challenging in unvaccinated communities. The preventive and organized surveillance programs for HPV screening are needed to be considered and compiled by health policy makers of low or unvaccinated countries.

The nutritional quality of food parcels provided by food banks and the effectiveness of food banks at reducing food insecurity in developed countries: a mixed-method systematic review.

BACKGROUND: Research indicates that food parcels provided by food banks are nutritionally poor. Food insecurity and the use of food banks are both rising, with detrimental effects on the dietary intake and health of users. This mixed-method systematic review aims to investigate the current nutritional adequacy of pre-packaged food parcels and whether using food banks reduces the food insecurity and improves the dietary intake of their users. METHODS: A mixed-method systematic literature review, restricted to articles published from 2015, was conducted using eight electronic databases, four grey literature databases and eight relevant websites. Quantitative findings, investigating the nutritional quality of food parcels and/or their impact on dietary intake or food insecurity, were presented narratively. Qualitative findings reporting the views of food bank users regarding food from food banks underwent thematic synthesis. These independent syntheses were integrated using configurative analysis and presented narratively. RESULTS: Of 2189 articles, 11 quantitative and 10 qualitative were included. Food parcels were inconsistent at meeting nutritional requirements and often failed to meet individual needs, including cultural and health preferences. Using food banks improved food security and dietary quality of users, allowing otherwise unachievable access to food. However, food insecurity remained, and is explained by limited food variety, quality and choice. The mixed-method findings support interventions to ensure consistent, adequate nutrition at food banks, including catering for individual needs. CONCLUSIONS: Food banks are a lifeline for those severely food insecure. However when used alone, food banks struggle to eliminate the heightened food insecurity of their users. Efforts to improve the nutritional quality of food parcels could improve the experiences and diet-related outcomes of those requiring food banks.

Mapping the evidence for monitoring fluoride exposure in community prevention programmes for oral health using nail clippings and spot urine samples: a scoping review.

BACKGROUND: There is an increased interest in identifying practical and accurate biomarkers for fluoride exposure. Due to the narrow 'dose-gap' between the benefit of caries reduction and the risk of dental fluorosis, monitoring of fluoride exposure is vital when introducing any fluoridation programme for the prevention of dental caries. This scoping review aimed to ascertain the nature and extent of the available evidence on how spot urine and nail clippings are used to measure fluoride intake/exposure, by using a unique approach of mapping the studies according to population, setting, type of study design, methodology and analytical approach in community prevention programmes. METHODS: Multiple relevant databases were searched up to July 2021 for any study designs, including randomised controlled studies, quasi-experimental studies, surveys, retrospective and prospective cohort studies, case studies, phenomenological studies, and expert opinions. RESULTS: The search retrieved 9,222 studies of which 155 met the inclusion criteria. A high proportion of the studies (25.2%) originated from Latin America and the Caribbean continent subregion. However, per country, China recorded the highest number, followed by India and Mexico. The majority (62.6%) employed a cross-sectional study design, and 65.8% combined participants from different age groups. Of the included studies, 82.6% used spot urine samples as a biomarker for assessing fluoride intake/exposure. Water fluoride concentration was reported in 66.5% of the studies with 46.6% of all included studies reporting a water fluoride concentration of > 1.2 mg/L. The methods used in assessing oral hygiene and dietary intake were not reported in 72.3% and 71.0% of the included studies, respectively. Only 35.5% of the included studies assessed the relationship between fluoride exposure and excretion. CONCLUSIONS: This review revealed a large variability in the way in which spot urine samples and/or nail clippings are used to measure fluoride exposure in different settings and situations. Particularly, there are inconsistencies in the methodologies and the analytical approaches used in assessing fluoride exposure. Therefore, there is a need for more rigorous primary research studies using standardised approaches to determine the suitability of spot urine samples and nail clipping as biomarkers for monitoring fluoride exposure.

The possible role of maternal and placental vitamin D receptor polymorphisms and haplotypes in pathogenesis of preeclampsia.

Purpose: Vitamin D deficiency may be a main causative agent in the pathogenesis of preeclampsia (PE). The actions of the active form of vitamin D are mediated via the vitamin D receptor (VDR), which is expressed in numerous organs including placenta. Therefore, we evaluated the potential relationship between maternal and placental VDR polymorphisms and the predisposition to PE in an Iranian population.Methods: This case-control study surveyed 152 PE and 160 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal and placental VDR Fok1 rs2228570, Bsm1 rs1544410, Taq1 rs731236, and Apa1 rs7975232 polymorphisms.Results: The maternal but not placental VDR FokI Ff genotype, was significantly lower in PE women (P = .02 and P = .06, respectively). The maternal and placental VDR FokI polymorphism was associated with lower PE risk in the dominant model (Ff+ff vs. FF) and these genotypes could decrease PE risk (OR, 0.5 [95% CI, 0.3-0.8], P = .007 and OR, 0.5 [95% CI, 0.3-0.9], P = .02, respectively). The haplotype analysis revealed that the maternal and placental TABf haplotype may lead to decreased risk of PE. In addition, the placental TABF haplotype was associated with higher risk of PE. No relationship was observed between PE susceptibility and the maternal and placental VDR Bsm1, Taq1 and Apa1 polymorphisms. There was also no relationship between the maternal and placental VDR polymorphisms and PE severity.Conclusions: the maternal and placental VDR FokI variant was associated with decreased risk of PE in the dominant model.

Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia.

The current study examined the effects of BAX and BCL2 polymorphisms and methylation as well as mRNA expression on susceptibility to PE. After delivery, the placentas were collected from 92 women with PE, as well as 106 normotensive pregnant women. The BAX rs4645878 and BCL2 rs2279115 polymorphisms were genotyped by the PCR-RFLP method. Methylation-specific PCR (MSP) was used for analysis of promoter methylation. mRNA expression was assayed by Quantitative RT-PCR. In addition, in silico analysis was performed by bioinformatics tools. There was no relationship between PE and placental BAX rs4645878 and BCL2 rs2279115 polymorphisms. The groups were not significantly different regarding the promoter methylation of BAX gene. Nonetheless, the MM status of BCL2 promoter had a significantly higher frequency in the PE group and was associated with 2.7-fold higher risk of PE (OR = 2.7, 95% CI = 1.3-5.6; P = 0.01). The relative mRNA expression of BCL2 was decreased in the placentas of PE women (P < 0.0001). The expression of BAX gene was not significantly different between the two groups. There was no association between placental BAX rs4645878 and BCL2 rs2279115 polymorphisms and mRNA expression levels. In silico analysis indicated that BAX rs4645878 and BCL2 rs2279115 polymorphisms were located in the core recognition site of different transcription factors and these substitutions of wild allele resulted in the loss and/ or change of these binding sites and subsequently may alter BCL2 and BAX expression. This study showed that the BAX and BCL2 polymorphisms and BAX promoter methylation were not associated with PE risk. The BCL2 promoter methylation was associated with lower BCL2 expression and higher PE susceptibility.

The effect of miR-146a rs2910164 and miR-149 rs2292832 polymorphisms on preeclampsia susceptibility.

Preeclampsia (PE) is a gestational disorder and genetic and epigenetic alterations can affect its pathogenesis. Some evidences showed that the altered expression of miRNAs in the placentas complicated by PE. The blood samples from 219 PE and 242 normotensive pregnant women and placental tissue samples from 111 PE and 119 normotensive women were collected. MiR-146a and miR-149 polymorphisms were genotyped in blood samples and placentas using PCR-RFLP method. The frequencies of maternal miR-146a rs2910164 GC and CC genotypes did not differ between PE and control groups. However, the miR-146a rs2910164 G/C polymorphism was associated with an increased risk of PE in dominant (OR 1.5, 95% CI 1-2.1; P = 0.04) and allelic (OR 1.4, 95% CI 1-1.9; P = 0.04) but not recessive models. Moreover, the maternal GC and CC genotypes were associated with a 1.9- and 3.4-fold increased risk of severe PE (OR 1.9, 95% CI 1.1-3.2; P = 0.02 and OR 3.4, 95% CI 1.3-9; P = 0.01, respectively) and miR-146a rs2910164 polymorphism could increase risk of severe PE in dominant and recessive models (OR 2.1, 95% CI 1.3-3.4; P = 0.004 and OR 2.6, 95% CI 1-6.7; P = 0.04). The placental miR-146a rs2910164 polymorphism was associated with PE susceptibility in dominant (OR 1.8, 95% CI 1.1-3; P = 0.03) and allelic models (OR 1.7, 95% CI 1.1-2.5; P = 0.02). The frequencies of maternal and placental miR-149 rs2292832 genotypes were not different between two groups and these genotypes were not associated with PE or severe PE risk. In conclusion, according to logistic regression analysis the maternal/placental miR-146a rs2910164 G/C polymorphism was associated with PE and/or severe PE risk.

The association of pri-miRNA- 26a1 rs7372209 polymorphism and Preeclampsia susceptibility.

MicroRNAs (miRNAs) are a class of noncoding small RNAs which regulate gene expression through post-transcriptional repression or degradation of messenger RNA. They play very important roles in various biological processes including growth, differentiation, and proliferation, as well as apoptosis, angiogenesis, and metabolism. Therefore, in the present study, we evaluated the possible effect of functional rs7372209C/T polymorphism in the 5'- region of pri-miRNA- 26a1gene on preeclampsia(PE) susceptibility. This case-control study was conducted on 219 PE women and 204 unrelated healthy controls. The amplification refractory mutation system-polymerase chain reaction method was used for rs7372209C/T genotyping. The pri-miRNA- 26a1 rs7372209CT genotype was associated with decreased PE risk (OR, 0.5 [95% CI, 0.3-0.8], P = 0.001). The frequency of rs7372209TT genotype did not differ between two groups. In addition, the pri-miRNA- 26a1 rs7372209 polymorphism was associated with lower risk of PE in dominant model (CT+TT vs CC) (OR, 0.5 [95% CI, 0.4-0.8], P = 0.002). Although there was no significant difference between mild and severe PE women according to rs7372209CT genotype, the differences between mild and severe PE groups with controls remained significant. The frequency of pri-miRNA-26a1 rs7372209CT genotype was not different between late-onset PE and early onset PE groups. The present study showed for the first time that the pri-miRNA- 26a1 rs7372209 polymorphism was associated with lower risk of mild and severe PE in the dominant model and this polymorphism could be a protective factor for PE susceptibility.

Experimental validation and computational modeling of anti-influenza effects of quercetin-3-O-α-L-rhamnopyranoside from indigenous south African medicinal plant Rapanea melanophloeos.

BACKGROUND: Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking. METHODS: MDCK cells were exposed to Q3R and 100CCID50/100 µl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R. RESULTS: The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of - 10.81, - 10.47, - 9.52, - 9.24 and - 8.78 Kcal/mol, respectively. CONCLUSIONS: Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

Relationships between Dicer 1 polymorphism and expression levels in the etiopathogenesis of preeclampsia.

Preeclampsia (PE) is a pregnancy-specific complication which is a major cause of maternal and fetal morbidity and mortality. Recent studies have shown the aberrant expression of microRNAs (miRNAs) in the placenta of patients with PE. Dicer1 is a key enzyme in the generation of small noncoding RNAs including miRNAs. The aim of this study is to investigate the relationship between maternal and placental Dicer1 rs3742330 polymorphism and placental Dicer1 mRNA expression in PE and normotensive pregnant women. The blood and placenta of PE pregnant and normotensive pregnant women were collected after delivery. Dicer1 rs3742330 polymorphism was genotyped using PCR-RFLP method. The mRNA expression levels were measured using quantitative real time PCR. The maternal Dicer1 rs3742330 polymorphism was not associated with PE or PE severity; however, the placental Dicer1 rs3742330 AG genotype was associated with two fold higher risk of PE and three fold higher risk of severe PE (P = 0.018 and P = 0.005, respectively). The relative mRNA expression of Dicer1 gene in the placenta did not differ between the two groups. In addition, the relative mRNA expression of Dicer1 gene was significantly lower in the placenta of women with rs3742330 AG+GG genotypes in the total population (P = 0.028) and PE women (P = 0.004), but not in the control group. In conclusion, there was a relationship between placental but not maternal Dicer1 rs3742330 polymorphism and PE. There was no difference in Dicer1 mRNA expression between the PE and control groups; however, it was significantly lower in the placenta of women with rs3742330 AG+GG genotypes.

Hypomethylation of the miRNA-34a gene promoter is associated with Severe Preeclampsia.

PURPOSE: PE is a pregnancy-specific complication, which genetic and epigenetic factors play key roles in its pathogenesis. DNA methylation is a main epigenetic alteration with important roles in gene regulation. Micro RNAs (miRNAs) as another member of epigenetic machinery regulate the gene expression and involve in different biological pathways including apoptosis and placental development. Therefore, the present study performed to assess the association between miRNA-34a promoter methylation and PE susceptibility. METHODS: The placenta of 104 PE pregnant women and 119 normotensive pregnant women were collected after delivery. The methylation status of the miRNA-34a promoter was assessed using Methylation Specific PCR (MSP). RESULTS: The frequency of the hemi-methylated (MU) miR-34a promoter was significantly lower in PE women compared to the controls (17.3 vs. 29.4%) (OR, 0.45 [95% CI, 0.2-0.9], P = 0.016). The overall methylation rate was 23.1% in PE women and 41.2% in the control group and was significantly lower in PE women (OR, 0.4 [95% CI, 0.2-0.8], P = 0.004). The frequency of hemi-methylated (MU) and overall methylated (MU+MM) promoter of miR-34a gene was significantly lower in severe PE but not in mild PE women compared to the controls [(OR, 0.3 [95% CI, 0.1-0.8], P = 0.02) and (OR, 0.3 [95% CI, 0.1-0.7], P = 0.009), respectively]. There was an association between hemi-methylated (MU) and overall methylated (MU+MM) promoter and late onset PE [(OR, 0.4 [95% CI, 0.2-0.9], P = 0.03) and (OR, 0.4 [95% CI, 0.2-0.8], P = 0.01), respectively]. CONCLUSIONS: An association was found between hypo-methylation of the miR-34a promoter and PE and PE severity.

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility.

PURPOSE: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. METHODS: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1-2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4-6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC-GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4-8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 - 2], P = 0.01). CONCLUSIONS: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC-GG combined genotype and C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.

Use of physical restraint: Nurses' knowledge, attitude, intention and practice and influencing factors.

AIMS AND OBJECTIVES: To investigate the knowledge, attitude, intention and practice of nurses towards physical restraint and factors influencing these variables. BACKGROUND: A literature review showed a lack of studies focused on the intention of nurses regarding physical restraint throughout the world. Considering that very little research on physical restraint use has been carried out in Malaysia, assessment of nurses' knowledge, attitude, intention and practice is necessary before developing a minimising programme in hospitals. DESIGN: A cross-sectional study was used. METHODS: A questionnaire to assess the knowledge, attitude, intention and practice was completed by all nurses (n = 309) in twelve wards of a teaching hospital in Kuala Lumpur. RESULTS: Moderate knowledge and attitude with strong intention to use physical restraint were found among the nurses. Less than half of nurses considered alternatives to physical restraint and most of them did not understand the reasons for the physical restraint. Nurses' academic qualification, read any information source during past year and nurses' work unit showed a significant association with nurses' knowledge. Multiple linear regression analysis found knowledge, attitude and intention were significantly associated with nurses' practice to use physical restraint. CONCLUSION: This study showed some important misunderstandings of nurses about using physical restraint and strong intention regarding using physical restraint. Findings of this study serve as a supporting reason for importance of educating nurses about the use of physical restraint. RELEVANCE TO CLINICAL PRACTICE: Exploring the knowledge, attitude, intention and current practice of nurses towards physical restraint is important so that an effective strategy can be formulated to minimise the use of physical restraints in hospitals.

From balance to imbalance: disruption of plasma glutathione concentration in micropapillary thyroid carcinoma.

BACKGROUND: Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. MATERIALS AND METHODS: Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. RESULTS: The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01). CONCLUSION: These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC.

Food insecurity in adults with severe mental illness living in Northern England: A co-produced cross-sectional study.

AIM: This study aimed to explore food insecurity prevalence and experiences of adults with severe mental illness living in Northern England. METHODS: This mixed-methods cross-sectional study took place between March and October 2022. Participants were adults with self-reported severe mental illness living in Northern England. The survey included demographic, health, and financial questions. Food insecurity was measured using the US Department of Agriculture Adult Food Security measure. Quantitative data were analysed using descriptive statistics and binary logistic regression; and qualitative data using content analysis. RESULTS: In total, 135 participants completed the survey, with a mean age of 44.7 years (SD: 14.1, range: 18-75 years). Participants were predominantly male (53.3%), white (88%) and from Yorkshire (50.4%). The food insecurity prevalence was 50.4% (n = 68). There was statistical significance in food insecurity status by region (p = 0.001); impacts of severe mental illness on activities of daily living (p = 0.02); and the Covid pandemic on food access (p < 0.001). The North West had the highest prevalence of food insecurity (73.3%); followed by the Humber and North East regions (66.7%); and Yorkshire (33.8%). In multivariable binary logistic regression, severe mental illness' impact on daily living was the only predictive variable for food insecurity (odds ratio = 4.618, 95% confidence interval: 1.071-19.924, p = 0.04). CONCLUSION: The prevalence of food insecurity in this study is higher than is reported in similar studies (41%). Mental health practitioners should routinely assess and monitor food insecurity in people living with severe mental illness. Further research should focus on food insecurity interventions in this population.