The Role of Prrx1 and Snai2 as Master Regulators of Fibroblast Identity

Mammalian development involves a complex system of regulatory signals and reactions, leading to the creation of distinct tissues with specific structures and functions controlled by various gene expression profiles. Tissue-specific gene expression is by controlled specific combinations of transcription factors and cofactors that dictate cell differentiation via activation and repression of genes in mammalian cells. Whole genome microarray analyses of fibroblasts have revealed candidate genes that may serve as master regulators of fibroblast identity, such as Prrx1 and Snai2, that activate downstream genes such as Bmp3, Twist, Shox2, Cfos, Slug, Sema3A, Spp1, and Col1a1. A previous study showed that Prrx1 and Snai2 play important roles in activating expression of fibroblast identity using somatic cell hybrids as model systems. Based on these results, we sought to examine the role of Prrx1 and Snai2 in affecting the phenotyope of liver-derived cells using hepatoma cells as a model system. Expression plasmids containing Prrx1 and Snai2 expression cassettes were transfected separately into Fg14 rat hepatoma cells using a standard transfection technique, then G418-resistant clones were selected (pooled and individually) and monitored for over-expression of Prrx1 and Snai2. RNA was extracted and used to synthesize cDNA. Quantitative real-time polymerase chain reaction (qPCR) was carried out using specific primer pairs and signals normalized to GAPDH mRNA levels. In addition, we observed alteration morphology and cell migration using Scratch Assays. qPCR analysis revealed that both Prrx1 and Snai2 were successfully over-expressed in pooled Fg14 transfectants and individual clones compared to non-transfected cells. Next we monitored expression of several genes known to be important in liver and fibroblast function. Results show that Snai2 activated several genes (Twist,Cfos,Shox2,and Bmp3) in Fg14 hepatoma cells. Although several other fibroblast genes (SEMA3A and Spp1) were relatively unaffected. Prrx1 overexpression resulted in activation of (Cfos,Twist,Shox2,Bmp3,and Col1a1) expression in Fg14 hepatoma, but (SEMA3A and Spp1) were unaffected. Based on these findings we hypothesized that overexpression of fibroblast-specific transcription factor Prrx1 and Snai2 would result in loss of hepatoma phenotype. We therefore monitored expression of a panel of liver-specific genes using qPCR analysis. Results show that several liver related genes are repressed by these transcription factors, leading to partial loss of the hepatic phenotype. We observed that the cells re-acquired a spindle-shaped morphology and more significantly an enhanced migration capability, which is reminiscent of parental fibroblast cells. In conclusion, these results suggest that candidate core Prrx1 and Snai2 serve as a useful starting point for studying transcriptional control of cell identity and reprogramming of mammalian cell types

Arabic translation and cultural adaptation of Liverpool Adverse Events Profile (LAEP) among a sample of epileptic older adults

Purpose: To validate and culturally adapt Liverpool Adverse Events Profile (LAEP) in Arabic among a sample of elderly patients with epilepsy.Methods: The face and content validity of the Arabic version of LAEP was ensured by a group of healthcare professionals. Undemented elderly patients (≥ 60 years) with seizure disorders, who are on a single antiepileptic drug (AED), were recruited from two tertiary care centers in Riyadh, Saudi Arabia. Factor analysis was performed to check the construct validity. The reliability was measured using Cronbach’s alpha method.Results: Seventy-four patients met the inclusion criteria and were interviewed. Most of the participants had generalized seizures (67.57 %), and were either illiterate or with elementary school education (62.16 %). Their mean age was 68.9 years, and 51.35 % were male. About two-thirds of the participants were on either carbamazepine or levetiracetam (66.22 %). Six factors were extracted from the Arabic version of LAEP. Cronbach’s alpha of the Arabic version of LAEP was 0.84. The mean overall LAEP score was 28.9.Conclusion: The Arabic version of LAEP demonstrates good validity and reliability. Similar studies should examine its validity and reliability among different epileptic patient populations.Keywords: Adverse drug event, Epilepsy, Older adults, Cronbach’s alpha, Liverpool Adverse Events Profile, Seizure disorders, Carbamazepine, Levetiraceta

Forensic Toxicology Laboratory Guidelines: Analytical Method Validation (Version 2.0)

Since postmortem forensic toxicology involves analyzing body fluids and organs from death cases, interpreting that information and studying the sudden unexpected and/or unexplained deaths as coroner’s cases or fall under the jurisdiction of the medical examiner. Reliable results and valid analytical data are an essential requirement for proper interpretation of forensic toxicology cases, especially when evaluating scientific studies and daily routine work, and when presenting any toxicological findings as criminal evidence. In contrast, the results of unreliable analyses can be disputed in court and can also lead to unfair legal judgments against the defendant, or can result in wrong treatment in cases of rehabilitation of patients. In order to establish strong evidence and make a correct decision, the lab is asked to give high quality data that are based on reliable analytical methods. For that reason, all new analytical methods used in forensic toxicology including the clinical diagnosis of causes of death require careful care during the development of the analytical method and during its application. This is also an urgent need in the context of quality management and accreditation, especially as those issues have become increasingly important in the science of poisons and drug analysis in recent years

ABCB1 variants C3435T and T129C are not associated with colorectal cancer risk

Background: Colorectal cancer (CRC) is one of the most prevalent cancers in Saudi Arabia that is highly characterized with poor survival rate and advanced metastasis. Many studies contribute this poor outcome to the expression of ABC transporters on the surface of cancer cells. Objectives: In this study, two ABCB1 variants, C3435T and T129C, were examined to evaluate their contribution to CRC risk. Methods: 125 subjects (62 CRC patients and 63 healthy controls) were involved. The DNA was isolated and analyzed with PCR-RFLP to determine the different genotypes. The hardy-Weinberg equilibrium was performed to determine genotype distribution and allele frequencies. Fisher\u2019s exact test (two-tailed) was used to compare allele frequencies between patients and control subjects. Results: The study showed that for SNP C3435T, the population of both CRC patients and controls were out of Hardy-Weinberg equilibrium. Genotype distribution for CRC patients was (Goodness of fit \u3c72 = 20, df= 1, P 640.05), whereas, for the controls the genotype distribution was (Goodness of fit \u3c72 = 21, df =1, P 640.05). For SNP T129C, all subjects showed normal (TT) genotype. Conclusion: There was no significant association between ABCB1 3435C>T and 129T>C polymorphisms with CRC risk

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Patterns in counselling services provided at Saudi Ministry of Health medication counselling clinics – Reasons for referrals and subjects discussed: A cross-sectional study

Background: Pharmacists provide medication counselling services to improve patient knowledge and their adherence to prescription instructions, and to achieve the best possible health-related outcomes. Our study aim was to describe the patterns of the reasons for referral to counselling and the subjects discussed between pharmacists and patients, and the possible associations related to the susceptible patient groups (chronic and elderly), in Saudi Ministry of Health (MOH) medication counselling clinics. Method: This was a descriptive cross-sectional study. An electronic data collection form was developed to document details about the medication counselling services that were provided to patients. The form consisted of three main areas: (1) patient demographics and counselling services characteristics; (2) reasons for referrals to the medication counselling clinics; and (3) the subjects that were discussed between pharmacists and patients in the counselling session. A comparison was conducted between chronic and non-chronic, and elderly and non-elderly patients. Results: From May 2020 to December 2021, a total of 36,672 counselling service sessions were provided to 28,998 patients. The greatest proportion of reasons for referrals to counselling was that patients had chronic diseases (50.84%), patients were added a new medication (33.69%) or patients received multiple medications (polypharmacy) (22.71%). The most frequent subject discussed during counselling was general knowledge about medication (85.62%), the duration of therapy (68.42%) and the action that patients should take if they missed a dose of their medication (44.51%). Patients with chronic diseases showed a significantly greater frequency of referral to counselling compared to patients without chronic disease, due to polypharmacy, medication use during Ramadhan, adverse drug reactions (ADRs), dosing/interactions, high-alert medication and suspected nonadherence (P < 0.001). This led to a significantly greater frequency of discussions with patients with chronic conditions about their general medication knowledge, the duration of their therapy, missed doses, ADRs, medication reconciliation and medication use during Ramadhan (P < 0.001). Elderly patients recorded significantly more referrals to counselling related to chronic diseases and polypharmacy than their younger counterparts (P < 0.001); however, there was no significant difference between the elderly and non-elderly in the patterns of subjects discussed that were related to polypharmacy and chronic disease consequences. A significant spike was also reported in the frequency of delivery of counselling services to caregivers for the elderly (P < 0.001). Conclusion: The current state of medication counselling services in Saudi MOH facilities indicates that chronic disease and polypharmacy are the most significant reasons for referral to counselling, and that the subjects discussed the most during counselling are general knowledge about medication, duration of therapy and missed doses. Patients with chronic diseases have a higher frequency of referral to counselling and discussion about polypharmacy and its consequences than those without chronic conditions. Elderly patients also show a high frequency of referral to counselling about chronic diseases and polypharmacy. Caregivers of elderly patients require more education to maximise counselling effectiveness as they attend the majority of elderly patient counselling sessions

Hemophagocytic Lymphohistiocytosis: Single-Center Series of 12 Cases from Saudi Arabia

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease that commonly appears in infancy, although it has been reported in adults. Chemoimmunotherapy-based treatments have improved the survival of patients with HLH; however, overall survival is still poor. We retrospectively analyzed the data of 12 HLH patients who were admitted between 2005 and 2014. All patients were Saudi Arabia in origin with a female predominance (75%) and a median age of onset of 9.5 months. The consanguinity rates were significantly high (75%) with a positive family history in 41% of cases. Of the 12 patients, nine were defined as primary HLH patients and three were confirmed to be secondary HLH patients. All patients fulfilled the 2004 diagnostic criteria for HLH and received HLH-2004 treatment. Six of these patients showed a good response to chemotherapy, while the remainder of the patients showed partial or no response to chemotherapy. Five patients in this cohort received stem cell transplant, and these patients are currently in remission. The mortality rate of this cohort is currently 50%. Genetic mutational analysis showed a positive STX11 mutation in five patients and a PRF1 ( perforin ) mutation in two patients. To the best of our knowledge, this is the first case series of HLH from Saudi Arabia

Image synthesis of apparel stitching defects using deep convolutional generative adversarial networks

In industrial manufacturing, the detection of stitching defects in fabric has become a pivotal stage in ensuring product quality. Deep learning-based fabric defect detection models have demonstrated remarkable accuracy, but they often require a vast amount of training data. Unfortunately, practical production lines typically lack a sufficient quantity of apparel stitching defect images due to limited research-industry collaboration and privacy concerns. To address this challenge, this study introduces an innovative approach based on DCGAN (Deep Convolutional Generative Adversarial Network), enabling the automatic generation of stitching defects in fabric. The evaluation encompasses both quantitative and qualitative assessments, supported by extensive comparative experiments. For validation of results, ten industrial experts marked 80% accuracy of the generated images. Moreover, Fréchet Inception Distance also inferred promising results. The outcomes, marked by high accuracy rate, underscore the effectiveness of proposed defect generation model. It demonstrates the ability to produce realistic stitching defective data, bridging the gap caused by data scarcity in practical industrial settings