Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients

Genetics of grain yield and its components in wheat under heat stress

Heat stress is a matter of a great concern for the wheat crop. Heat stress usually either hastens crop development or shortens the grain filling duration, which severely reduces grain yield. Being a complex trait, understanding the genetics and gene interactions of stress tolerance are the two primary requirements for improving yield levels. Genetic analysis through generation mean analysis helps to find out the nature of gene actions involved in a concerned trait by providing an estimate of main gene effects (additive and dominance) along with their digenic interactions (additive × additive, additive × dominance, and dominance × dominance). In the present investigation, we elucidated the inheritance pattern of different yield contributing traits under heat stress using different cross combinations which could be helpful for selecting a suitable breeding strategy. Thus six generations of five crosses were sown normal (non-stress, TS) and late (heat stress, LS) in a randomized block design with three replications during two crop seasons. The model was not adequate for late sown conditions indicating the expression of epistatic genes under stress conditions. The traits i.e. Days to heading (DH), Days to anthesis (DA), Days to maturity (DM), Grain filling duration (GFD), Grain yield (GY), Thousand grain weight (TGW), Grain weight per spike (GWS) and Heat susceptibility index (HSI) under heat stress conditions were found under the control of additive gene action with dominance × dominance interaction, additive gene action with additive × dominance epistatic effect, dominance gene action with additive × additive interaction effect, additive and dominance gene action with dominance × dominance interaction effect, additive gene action with additive × dominance epistatic effect, additive gene action with additive × additive interaction effect and dominance gene action with additive × additive interaction effect, respectively

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

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

Neural Fractional Order PID Controllers Design for 2-Link Rigid Robot Manipulator

The robotic manipulator is considered one of the complex systems that include multi-input, multi-output, non-linearity, and highly coupled. The uncertainty in the parameters and external disturbances have a negative influence on the performance of the system. Therefore, the controllers that will be designed for these systems must be able to deal with these complexities and difficulties. The Proportional, Integral, and Derivative (PID) controller is known to be simple and well robust, while the neural network has a solid ability to map complex functions. In this paper, we propose six control structures by combining the benefits of PID controller with integer and fractional order and the benefits of neural networks to produce hybrid controllers for a 2-Link Rigid Robot Manipulator (2-LRRM) handling with the problem of trajectory tracking. The Gorilla Forces Troops Optimization algorithm (GTO) was used to tune the parameters of the proposed controller schemes to minimize the Integral of Time Square Error (ITSE). In addition, the robustness of the performance of the suggested control systems is tested by altering the initial position, external disturbances and parameters and carried out using MATLAB. The best performance of the proposed controllers was the Neural Network Fractional Order Proportional Integral Derivative Controller (NNFOPID)

Sunscreen behaviors among Libyan society survey

Sunscreen products are available in wide scale for consumers, the topical use products act by either absorbing or scattering the UV radiation. Excessive UV radiation exposure have been shown to be associated with a series of dermatologic disorders, which symptoms may appear instantly, or even developed few years later in life. The objective of this study is to assess the behaviors, application and use- base of sunscreen. A questionnaire-based study was conducted in Tripoli province, Libya. The questionnaire included four broad categories, developed to explore and highlight the main behaviors during the use and application of sunscreen. Questionnaire circulated inside dermatology follow-up clinics and outside hospital. Respondent characteristics pattern reported as a percentages. Data were analyzed from 385 participants who had complete information regarding behaviors and use of sunscreen at Libyan society. With at least 70% of participants using and applying sunscreen, the majority of users were female 87.8%, and their age ranges from 20 to29 years, with frequent use more than 2 times per week. Whereas 57% of participants applied sunscreen as personal protection of their skin. In this survey, the questionnaire-based study provided valuable information about the behaviors and habits of applying sunscreen products. The majority of participants applied sunscreen to protect their skin, the market drives the users about the type of sunscreen and most of the participants gave the medical counsel and recommendation low attention

The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank.

Coronavirus Disease 2019 (COVID-19) manifestations range from mild to severe life-threatening symptoms, including death. COVID-19 susceptibility has been associated with various factors, but studies in Qatar are limited. The objective of this study was to investigate the correlation between COVID-19 susceptibility and various sociodemographic and lifestyle factors, including age, gender, body mass index, smoking status, education level, dietary patterns, supplement usage, physical activity, a history of bariatric surgery, diabetes, and hypertension. We utilized logistic regression to analyze these associations, using the data of 10,000 adult participants, aged from 18 to 79, from Qatar Biobank. In total, 10.5% ( = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR] = 0.55; 95% CI: 0.44-0.68 and OR = 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction in the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥ 30 kg/m), a history of bariatric surgery, and higher adherence to the modern dietary pattern-characterized by the consumption of foods high in saturated fat and refined carbohydrates-were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.Qatar National Research Fund (QNRF) grant number RRC02-0807-210,022 to A.A.S. The funding source (QNRF) had no role in study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the article for publication. Institutional Review Board Statement This study was approved by Qatar University IRB (QU-IRB 1779-E/22, 11 October 2022) and QBB IRB (EX-2021-QF-QBB-RES-ACC-00065-0181, 25 October 2022)

Exposure to Methylmercury at Juvenile Stage Worsens Autism-like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain

Autism spectrum disorder (ASD) is a multifaceted developmental condition that first appears in infancy. The condition is characterized by recurrent patterns in behavior and impairments in social and vocalization abilities. Methylmercury is a toxic environmental pollutant, and its derivatives are the major source of organic mercury to human beings. Inorganic mercury, which is released from a variety of pollutants into oceans, rivers, and streams, is transformed into methylmercury by bacteria and plankton in the water, which later builds up in fish and shellfish, and then enters humans through the consumption of fish and shellfish and increases the risk of developing ASD by disturbing the oxidant–antioxidant balance. However, there has been no prior research to determine the effect of juvenile exposure of methylmercury chloride on adult BTBR mice. Therefore, the current study evaluated the effect of methylmercury chloride administered during the juvenile stage on autism-like behavior (three-chambered sociability, marble burying, self-grooming tests) and oxidant–antioxidant balance (specifically Nrf2, HO-1, SOD-1, NF-kB, iNOS, MPO, and 3-nitrotyrosine) in the peripheral neutrophils and cortex of adult BTBR and C57BL/6 (B6) mice. Our results show that exposure to methylmercury chloride at a juvenile stage results in autism-like symptoms in adult BTBR mice which are related to a lack of upregulation of the Nrf2 signaling pathway as demonstrated by no significant changes in the expression of Nrf2, HO-1, and SOD-1 in the periphery and cortex. On the other hand, methylmercury chloride administration at a juvenile stage increased oxidative inflammation as depicted by a significant increase in the levels of NF-kB, iNOS, MPO, and 3-nitrotyrosine in the periphery and cortex of adult BTBR mice. This study suggests that juvenile exposure to methylmercury chloride contributes to the worsening of autism-like behavior in adult BTBR mice through the disruption of the oxidant–antioxidant balance in the peripheral compartment and CNS. Strategies that elevate Nrf2 signaling may be useful to counteract toxicant-mediated worsening of ASD and may improve quality of life