Interaction of Per- and Polyfluoroalkyl Substances with Estrogen Receptors in Rainbow Trout (Oncorhynchus mykiss): An In Silico Investigation.

Fresh water sources, including lakes, such as the Great Lakes, are some of the most important ecosystems in the world. Despite the importance of these lakes, there is increasing concern about the presence of per- and polyfluoroalkyl substances (PFAS)─among the most prevalent contaminants of our time─due to the ability of PFAS to bioaccumulate and persist in the environment, as well as to its linkages to detrimental human and animal health effects. In this study, PFAS exposure on rainbow trout (Oncorhynchus mykiss) is examined at the molecular level, focusing on the impact of PFAS binding on the alpha (α) and beta (ß) estrogen receptors (ERs) using molecular dynamics simulations, binding free energy calculations, and structural analysis. ERs are involved in fundamental physiological processes, including reproductive system development, muscle regeneration, and immunity. This study shows that PFAS binds to both the estrogen α and estrogen ß receptors, albeit via different binding modes, due to a modification of an amino acid in the binding site as a result of a reorientation of residues in the binding pocket. As ER overactivation can occur through environmental toxins and pollutants, this study provides insights into the influence of different types of PFAS on protein function.

Analysis of circulating osteoclast and osteogenic precursors in patients with Gorham-Stout disease.

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients. METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin). RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN. CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.

Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.

BACKGROUND: Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer. METHODS: Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder. RESULTS: High SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047). CONCLUSION: Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.

Media use, dietary intake, and diet quality of adolescents in Saudi Arabia.

BACKGROUND: Excessive media use can affect diet of adolescents, but relevant data in Saudi Arabia are lacking. The present study aimed to explore the association between media use, dietary intake, and diet quality among adolescents. METHODS: This cross-sectional study included data of 631 adolescents (ages 11-18 years) who were randomly recruited from 16 schools located in two main cities in the Western region of Saudi Arabia (Madinah and Jeddah). Envelopes including a questionnaire were sent home to collect sociodemographic data. Students then completed the short-form food frequency questionnaire to assess diet quality. Data on media use, anthropometrics, and 24-h dietary recalls were also collected. RESULTS: A high proportion of adolescents (86.2%) exceeded media use recommendations of ≤2 h per day. Significantly higher proportions of younger adolescents, males, and non-Saudis reported media use within the recommendation compared to their peers. Media use predicted lower diet quality score (B = -0.67 [95% CI: -1.09 to -0.28]) and lower intake of calcium, zinc, vitamin D, and vitamin C (B = -104 [95% CI: -203 to -5.24], B = -2.13 [95% CI: -4.15 to -0.11], B = -23.5 [95% CI: -41.3 to -5.65], B = -24.0 [95% CI: -45.1 to -2.96], respectively). CONCLUSION: Interventions to limit media use are urgently needed for adolescents in Saudi Arabia to improve diet quality and overall nutritional health. IMPACT: Excessive media use can affect diet of adolescents, but relevant data are lacking in Saudi Arabia. The majority of adolescents exceed the recommendations for media use. Media use was negatively associated with diet quality and intake of calcium, zinc, vitamin D, and vitamin C. This study will inform public health entities and policy makers to draw evidence-based, culturally tailored recommendations and develop nutrition interventions to enhance diet quality and nutritional status of adolescents. Findings of this study highlight the urgency to develop intervention programs and policies that aim to limit media use among adolescents.

Estimation of diversity and combining abilities in Helianthus annuus L. under water stress and normal conditions.

Sunflower cannot produce high yields under water-limiting conditions. The aim of the present study was to prevent the impediments on yield and to develop varieties with high-yield potential under water scarce conditions. For achieving this objective, it is necessary to detect parents with desirable traits that mainly depend on the action of genes controlling the trait under improvement, combining ability, and genetic makeup of the parents. Heterosis can also be used to pool the desirable genes from genetically divergent varieties and these divergent parents could be detected by molecular studies. Ten tolerant and five susceptible tester lines were selected, crossed, and tested for genetic diversity using simple sequence repeat primers. We identified two parents (A-10.8 and G-60) that showed maximum (46.7%) genetic dissimilarity. On an average 3.1 alleles per locus were detected for twenty pair of primers. Evaluation of mean values revealed that under stress conditions the mean performances of the genotypes were reduced for all traits under study. Parent A-10.8 was consistent as a good general combiner for achene yield per plant under both non-stress and stress conditions. Line A-10.8 in the hybrid A-10.8 x G-60 proved to be a good combiner as it showed negative specific combining ability (SCA) effects for plant height and internodal length and positive SCA effects for head weight, achene yield per plant, and membrane stability index. Valuable information on gene action, combining ability, and heterosis was generated, which could be used in further breeding programs.

Role of Toll-like receptor 2 (-196 to -174) polymorphism in susceptibility to pulmonary tuberculosis in Pakistani population.

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide. Pakistan ranks sixth on the list of 22 high-burden tuberculosis countries in the world. The transitions from infection to clinical disease are very few signifying that host-defence factors could lead to the development of active disease. Toll-like receptor (TLR) 2 polymorphisms have been associated with regulation of TLR expression and development of active TB. In this study, blood samples of 187 subjects including 100 healthy and 87 TB positive were collected from three districts of Pakistan. DNA was extracted from blood and TLR 2 (-196 to -174del) polymorphism was analysed by polymerase chain reaction (PCR). The results suggest that the frequency of -196 to -174del/del polymorphism of TLR2 was significantly higher in TB-positive patients compared with healthy. Results revealed that (-196 to -174del) polymorphism may increase the susceptibility to TB in healthy population of Pakistan. Moreover, males with heterozygous genotype (I/D) are more prone to TB than females with the same genotype. The occurrence of TB infection has been found positively associated with the age, suggesting that the population within the range of 21-45 years is more susceptible to Mycobacterium tuberculosis than other age groups studied. A significant association is also observed between smoking and the chances of developing TB, confirming that smoking strongly promotes its incidence.

Innovative surgical precision: The electronic pen needle holder based on neurophysiological principles.

Background: The electronic pen needle holder (EPNH) was developed to enhance surgical precision, reduce operative time, and improve patient outcomes. By integrating microergonomics, penization, and electronics with surgical instruments, the EPNH aims to provide surgeons with a tool that minimizes hand strain and maximizes control during delicate procedures. Methods: The EPNH was ergonomically designed to fit the surgeon's hand, using titanium for its strength and biocompatibility. It was manufactured through industrial-grade 3D printing, and its mechanical properties were verified using finite element analysis. A force-sensitive resistor and vibratory mechanism were integrated to provide real-time feedback and assistance during surgeries. Results: Testing by 10 neurosurgeons demonstrated significant precision, control, and efficiency improvements. The EPNH reduced hand strain and fatigue, allowing longer, more comfortable operation times. The time required for suturing tasks has decreased by 40% compared to traditional needle holders. Surgeons reported high satisfaction with the EPNH's performance and usability. Conclusion: The EPNH represents a major advancement in surgical instrument design, offering enhanced precision, reduced hand strain, and increased efficiency. Its innovative features and ergonomic design make it a valuable tool for improving surgical outcomes and transforming microsurgical practices.

Comparative Study on the Chemical Composition and Biological Activities of the Essential Oils of Lavandula angustifolia and Lavandula x intermedia Cultivated in Lebanon.

The phytochemical profile of essential oils is influenced by genetic and paragenetic factors. In this research, we studied the essential oils of Lavandula angustifolia and Lavandula x intermedia cultivated in Lebanon. The latter is a cross hybrid between Lavandula angustifolia and Lavandula latifolia and is also known as lavandin and Lavandula hybrida. Specifically, the chemical composition and biological activities (antibacterial, antioxidant, anticancer, and hemolytic) of the essential oils were assessed. GC-MS results showed marked differences in the chemical compositions of the oils. For example, linalool was more abundant in L. x intermedia (44.15%) than in L. angustifolia (32%), while an opposite trend was observed for the percentages of 1,8-cineole (8.6% in L. angustifolia and 4.0% in L. x intermedia). FTIR analysis confirmed the richness of both oils in monoterpenes and sesquiterpenes. In terms of antioxidant activity, L. angustifolia essential oil demonstrated significantly better activity (IC50= 5.24 ± 1.20 mg/mL) compared to L. x intermedia oil in the DPPH radical scavenging assay. MTT cell viability assays revealed that L. angustifolia essential oil was a slightly more potent antiproliferative agent than L. x intermedia oil on human colorectal (HCT-116) and human breast (MCF-7) cancer cells. The antibacterial activity of the essential oils was tested against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Serratia marcescens. Both oils showed good antibacterial activities with MIC values of 0.174 and 0.169 mg/mL for L. angustifolia and L. x intermedia oils, respectively. MBC determinations revealed that the antibacterial activity was bactericidal against all bacteria, except Staphylococcus aureus. Furthermore, both essential oils did not exhibit notable hemolytic activity on red blood cells. Overall, Lebanese L. angustifolia and L. x intermedia essential oils have promising industrial and medicinal values.

Enhancing orthodontic treatment control with fish scale-derived hydroxyapatite nanoparticles: Insights from an animal model study.

Objectives: This study investigates the impact of injected fish-scale-derived hydroxyapatite nanoparticles (FsHA-NPs) on orthodontic tooth movement (OTM) and the width of the periodontal ligament (PDL) space. Materials and Methods: Twenty-six Wistar rats underwent mesial orthodontic traction with a force of 50 g for 21 days. Following the application of the orthodontic appliance, the rats were randomly divided into two groups: a control group, which received a 0.3 µg saline injection, and the experimental FsHA group, which received 100 mg/0.3 ml of FsHA-NPs after thorough characterisation. Injections were administered immediately after appliance application and repeated at 7 and 14 days. Statistical analysis was conducted with a significance level of P ≤ 0.05. Result: The experimental group exhibited a significant reduction in OTM at 7-, 14-, and 21-day post-force application. Additionally, a reduction in PDL width was observed in the mesiocervical and disto-apical regions of the mesial and distal roots of the first molar. Conclusion: FsHA-NPs derived from biowaste fish scales exhibit promising potential as biomaterials for enhancing control over OTM. This study underscores the viability, accessibility, and safety of FsHA-NPs as a locally injectable material for orthodontic applications.

Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE.

BACKGROUND: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC. PATIENTS AND METHODS: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively. RESULTS: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D. CONCLUSIONS: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2. TRIAL REGISTRATION: NCT03812796 (registered 23rd January 2019).

Knowledge, attitude, and perception of robotic-assisted surgery among the general population in Saudi Arabia: a cross-sectional study.

Minimally invasive surgery (MIS) has revolutionized surgical practices, with robotic-assisted surgery (RAS) significantly advancing. However, the understanding and acceptance of RAS vary, impacting its widespread adoption. This study aims to assess Saudi Arabians' attitudes and comprehension of RAS, which is crucial for promoting its integration into surgical procedures. A cross-sectional study was conducted in various Saudi Arabian cities. A total of 1449 participants were included, while participants with cognitive issues were excluded. Demographic information, knowledge, technology experience, attitudes, and perceptions about RAS were collected using an online self-administered questionnaire. Data were analyzed using descriptive and inferential statistics. Of the participants, 51.1% demonstrated awareness of RAS, mainly through social media (36.9%). Factors influencing awareness included gender, education, income, occupation, computer literacy, and technology comfort. Gender disparities were evident in attitudes and perceptions toward RAS. Concerns about RAS included robot malfunction (62.0%), surgical errors (45.4%), and surgeon competency (44.7%). 36.4% of the participants believe RAS is faster, 29.9% believe RAS is less painful, and 25.3% believe RAS has fewer complications. Positive perceptions encompassed the belief that robot-using surgeons are more skilled (44.5%) and hospitals offering RAS are better (54.3%). Notably, 47.7% expressed willingness to consider RAS as a treatment option. The study underscores the significance of promoting awareness and informed decisions to ensure the successful integration of RAS in surgical practices. Addressing concerns and misconceptions and enhancing public comprehension are pivotal for facilitating informed decision-making and fostering RAS acceptance within Saudi Arabia's surgical landscape.

Comparing machine learning screening approaches using clinical data and cytokine profiles for COVID-19 in resource-limited and resource-abundant settings.

Accurate screening of COVID-19 infection status for symptomatic patients is a critical public health task. Although molecular and antigen tests now exist for COVID-19, in resource-limited settings, screening tests are often not available. Furthermore, during the early stages of the pandemic tests were not available in any capacity. We utilized an automated machine learning (ML) approach to train and evaluate thousands of models on a clinical dataset consisting of commonly available clinical and laboratory data, along with cytokine profiles for patients (n = 150). These models were then further tested for generalizability on an out-of-sample secondary dataset (n = 120). We were able to develop a ML model for rapid and reliable screening of patients as COVID-19 positive or negative using three approaches: commonly available clinical and laboratory data, a cytokine profile, and a combination of the common data and cytokine profile. Of the tens of thousands of models automatically tested for the three approaches, all three approaches demonstrated > 92% sensitivity and > 88 specificity while our highest performing model achieved 95.6% sensitivity and 98.1% specificity. These models represent a potential effective deployable solution for COVID-19 status classification for symptomatic patients in resource-limited settings and provide proof-of-concept for rapid development of screening tools for novel emerging infectious diseases.

Utilisation of the health belief model to study the behavioural intentions relating to obesity management among university students: a cross-sectional study.

BACKGROUND: Overweight and obesity are excessive fat accumulations linked with many health problems, including heart diseases, type 2 diabetes and cancer. Multiple studies have demonstrated that beliefs about overweight, obesity and self-efficacy play essential roles in the success of interventions for obesity management. OBJECTIVES: This study aimed to identify the perceptions of university students of overweight and obesity using the health belief model (HBM) and to analyse their association with the body mass index (BMI) categories of the students. DESIGN: A cross-sectional questionnaire-based study and a multistage sampling technique were used to ensure the recruitment of students from selected colleges of Jazan University-Saudi Arabia. SETTING: Six colleges of Jazan University were randomly selected to ensure equal representation of health sciences, sciences and humanities colleges. PARTICIPANTS: A total of 579 students completed an online survey between January and April 2023. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were demographic characteristics and HBM constructs. Secondary outcome measures were behavioural intentions relating to obesity management. RESULTS: This study demonstrated that gender and self-reported family history of obesity were significantly correlated with the BMI categories of the students (p <0.001). Students in the underweight category showed the highest mean score for perceived severity (3.62 ±0.08). Perceived self-efficacy in exercise and diet was significantly associated with BMI categories, with adjusted ORs of 2.82 (2.10 to 3.79) and 1.51 (1.09 to 2.09), respectively. Perceived barriers to healthy eating and regular physical activity were significantly related to the behavioural intentions of obesity management. Multivariate logistic regression showed that perceived severity, perceived cues to action, perceived barriers and self-efficacy in dieting and exercise were significant predictors of behavioural intentions for the management of obesity. CONCLUSION: This study underscores the need for tailored health promotion strategies that consider the perceptions and beliefs of people about the management of obesity.

A one-health approach to design an mRNA-based vaccine candidate against the lumpy skin disease virus as an alternative to live-attenuated vaccines.

OBJECTIVE: Recently, lumpy skin disease (LSD) has been spread over the Asian, European, and Middle Eastern regions making it a significant hazard to the chain of cattle production, milk production, and human milk consumption, requiring prompt attention. Lumpy skin disease virus has high morbidity and low fatality rates, but its infections have led to terrible economic and agricultural consequences. Although live-attenuated vaccines have been commercialized, farmers in different regions have not taken them well because of the allergic responses against the vaccines. The study aims to develop an mRNA-based vaccine candidate for LSDV, using immunoinformatic approaches to minimize allergenicity and homology while maximizing immunogenic potential. MATERIALS AND METHODS: The study used extensive immunoinformatic approaches to shortlist five proteins from the LSDV genome that belong to the transmembrane region and are crucial in early viral interaction with host cells. The B-cell and T-cell-specific epitopes were chosen based on non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. The construct's stability, hydrophilicity, and antigenic potential were analyzed using the instability index, Grand Average of Hydropathicity (GRAVY) index, and antigenicity, respectively. RESULTS: We selected a total of 34 epitopes, consisting of 12 B-cell-specific epitopes and 22 T-cell-specific epitopes. These epitopes were chosen based on their characteristics such as non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. Specifically, 11 epitopes were selected for Major Histocompatibility Complex-I, and another 11 epitopes were chosen for Major Histocompatibility Complex-II. The inclusion of the RS09 adjuvant enhanced the immunogenic potential of the vaccine. The instability index was found to be 38.60. Additionally, the GRAVY index, indicating hydrophilicity, was calculated as -0.151. Furthermore, the antigenicity value of 0.6073 confirmed its potential to elicit an immune response. Further supporting its immunogenic potential, strong immune stimulation was observed, with IgM+IgG titers reaching 6,000 (arbitrary units) and IFNg titers measuring 400,000 ng/mL. These results provide additional evidence of the vaccine's ability to stimulate a robust immune response. CONCLUSIONS: The study results indicate that the developed mRNA-based vaccine candidate for LSDV has high immunogenic potential and could serve as an effective alternative to live-attenuated vaccines. Further experimental validations are required to test its efficacy. The study also highlights the potential of the One-Health approach to tackle non-zoonotic diseases that have significant consequences for the environment and humanity.

Reported Symptoms and Associated Factors of Carpal Tunnel Syndrome in Qassim Region: A Cross-Sectional Study.

Background Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, occurring through compression of the median nerve as it passes under the transverse carpal ligament. Symptoms include nocturnal pain and paresthesias confined to the thumb, middle, and index fingers. Objective The purpose of this study is to determine the prevalence of CTS symptoms and the associated risk factors in Qassim Province, Kingdom of Saudi Arabia. Materials and methods A total of 314 participants were recruited from Qassim Province using an online survey, which included demographic questions and the Boston Carpal Tunnel Questionnaire (BCTQ). The association between categorical variables was assessed using the Chi-square test or Fisher's exact test, as appropriate. Additionally, an independent t-test was performed to compare quantitative variables. A p-value of less than 0.05 was considered statistically significant. Result The prevalence of CTS in the Qassim population was found to be 19.7%. The most significant risk factors for CTS were age, chronic illnesses, and employment status (p < 0.001). The most frequently reported symptoms included daytime pain and weakness (82.3%), while obesity emerged as the most prevalent chronic disease (21%). The mean symptom severity score (SSS) was significantly higher for individuals who were awoken from pain (t = -5.89; p < 0.001) and for those who experienced awakening due to numbness and tingling (t = -5.59; p < 0.001). Conclusion According to our sampled cohort, 19.7% of individuals had symptoms of CTS etiology. Multiple risk factors for CTS were identified. Notably, the development of CTS symptoms was significantly associated with individuals aged 50 and older, employment status, and the presence of related chronic diseases.

Association Between Subclinical Hypothyroidism and the Prognosis of Diabetes Mellitus and Subsequent Complications: A Retrospective Cohort Study.

Background Diabetes mellitus (DM) and subclinical hypothyroidism (SCH) are prevalent metabolic and endocrine disorders. Previous studies have suggested potential associations between SCH and metabolic disorders, including DM. This study aimed to explore the relationship between SCH and DM in patients from the Qassim Region in Saudi Arabia. Methods A retrospective cohort study was conducted on patients who attended the Qassim University clinics from December 2017 to December 2021. Participants were divided into two groups: SCH patients without a history of DM and age- and sex-matched controls without SCH or DM. Parameters, such as DM occurrence, DM duration, glycosylated hemoglobin (HbA1c) values, and metformin use, were evaluated. Results The prevalence of DM was 70.4% in the SCH group and 83.3% in the non-SCH group, with no significant difference between the groups (p=0.203). The mean HbA1c values and DM duration showed no significant variations between the two groups. However, metformin use was significantly higher in the SCH group at 74.1% compared to 50.0% in the non-SCH group (p=0.047). No correlation was observed between HbA1c and thyroid-stimulating hormone (TSH) levels. Conclusions While the study indicates a potential association between SCH and DM management, especially with regard to metformin usage, there does not appear to be a significant relationship between SCH and DM development or progression in this population.

The Prevalence and Impact of Allergic Rhinitis on Asthma Exacerbations in Asthmatic Adult Patients in the Qassim Region of Saudi Arabia: A Cross-Sectional Study.

Objective We aim to evaluate the prevalence and impact of allergic rhinitis comorbidity in asthmatic patients in the Qassim region and identify whether rhinitis affects asthma control. Methods This is an observational cross-sectional study on asthmatic adults who live in the Qassim region of Saudi Arabia. An online questionnaire was distributed through social media. The questionnaire is composed of the validated Arabic versions of the Score for Allergic Rhinitis (SFAR) questionnaire, the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines, and the Asthma Control Test (ACT) questionnaire. Results The total number of participants was 380; however, after 98 were excluded, 282 asthmatic patients were included in this study. Of them, 33% had allergic rhinitis. Females constitute 67% of the study participants, while males comprise 33%. The findings of the study indicate that there is a significant association between allergic rhinitis and asthma control in the Qassim region. Symptoms such as runny nose, sneezing, and nasal obstruction are significantly associated with poor asthma control (p = 0.006). Having a known family history of asthma, eczema, or allergic rhinitis is significantly associated with worse asthma control (0.004). Conclusion In summary, this study found a high prevalence of rhinitis symptoms comorbidity in asthmatic patients in the Qassim region. Overall, the study established the existence of a relationship between allergic rhinitis and asthmatic control. Symptoms such as a runny nose, sneezing, and nasal obstruction are significantly associated with allergic rhinitis and asthmatic symptoms. However, there is no significant association between nose problems that occur in specific seasons or months and allergic rhinitis and asthmatic symptoms, suggesting that seasonality may not have a strong impact on asthma control. House dust mite allergies have a borderline significant association with allergic rhinitis and asthmatic symptoms. Having a family history of asthma, eczema, or allergic rhinitis is associated with allergic rhinitis and asthmatic symptoms, thereby indicating a significant impact on asthma control.

Establishment of an in vitro regeneration system for genetic transformation of selected sugarcane genotypes.

A good culture system provides considerable quantities of highly regenerable target tissues. Embryogenic callus cultures are ideal for micro-projectile-mediated transformation, because regenerable cells are not very stable. Effective exploitation of genetic transformation requires good regeneration systems. We selected three sugarcane genotypes for the establishment and optimization of good in vitro regeneration systems, viz., S-2003-us-359, S-2006-sp-30, and S-2003-us-165. Three callus induction media were investigated. These media were composed of Murashige and Skoog (MS) medium salt plus 1, 2, and 3 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D). Medium with 3 mg/L 2,4-D gave the greatest mass of embryogenic calli. The calli produced on the three callus induction media were transferred to 18 types of regeneration media (RM1-RM18). They varied with respect to plant growth regulators and sucrose levels but the basal medium was MS. Two levels of sucrose (30 and 40 g/L), three levels of 2,4-D (0.1, 0.25, 0.5 mg/L) and three levels of 6-benzylaminopurine (0, 0.25 and 0.5 mg/L) were studied in the regeneration media. The effects of callus age on regeneration were evaluated by transferring the calli to regeneration media after 15, 21, 28, and 35 days of culture. The 21-day-old callus of the genotype S-2003-us-359 on RM3 yielded the largest number of plants and was selected as the best for transformation. Six RAPD DNA primers were used to check genetic stability; this medium did not affect the sugarcane genomes.

Serum interleukin-33 (IL-33) in children with active systemic lupus erythematosus: A cross-sectional study.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is associated with the development of different autoimmune diseases as systemic lupus erythematosus (SLE). So, the purpose of this cross-sectional study was to measure the serum IL-33 in children with SLE (c-SLE) in relation to their SLE disease activity index. This study was conducted upon 50 c-SLE patients in comparison to 50 normal matched children as a control group. Disease activity was assessed according to SLE Disease Activity Index (SLEDAI-2K). Serum IL-33 was measured by an Enzyme-linked immunosorbent assay (ELISA). Serum IL-33 was significantly higher in c-SLE patients (median: 157.47, IQR:64.49-237.57ng/l) than controls (median: 10.9, IQR: 10.04-12.51ng/L) (P= 0.001) and negatively correlated with serum C3 and C4 levels. Serum IL-33 levels were significantly higher in high disease activity status (HDAS) patients (SLEDAI-2K ≥ 10) (298.47 ± 78.84ng/l) than lupus low disease activity status (LLDAS) patients (SLEDAI-2K < 10) (112.18 ± 16.23ng/l) (P= 0.001). The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff of serum IL-33 level to predict the disease activity was ≥141.3 ng/l with a sensitivity of 93%, a specificity of 90% and accuracy 97%. We concluded that serum IL-33 was higher in c-SLE patients and positively related to the disease activity index so could be used as a disease activity marker.

Rare Heterogeneous Adverse Events Associated with mRNA-Based COVID-19 Vaccines: A Systematic Review.

Background: Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published literature, passive surveillance systems, and other pharmacovigilance platforms of a broad spectrum of adverse events following COVID-19 vaccination. A comprehensive review of the more serious adverse events associated with the Pfizer-BioNTech and Moderna mRNA vaccines is warranted, given the massive number of vaccine doses administered worldwide and the novel mechanism of action of these mRNA vaccines in the healthcare industry. Methods: A systematic review of the literature was conducted to identify relevant studies that have reported mRNA COVID-19 vaccine-related adverse events. Results: Serious and severe adverse events following mRNA COVID-19 vaccinations are rare. While a definitive causal relationship was not established in most cases, important adverse events associated with post-vaccination included rare and non-fatal myocarditis and pericarditis in younger vaccine recipients, thrombocytopenia, neurological effects such as seizures and orofacial events, skin reactions, and allergic hypersensitivities. Conclusions: As a relatively new set of vaccines already administered to billions of people, COVID-19 mRNA-based vaccines are generally safe and efficacious. Further studies on long-term adverse events and other unpredictable reactions in close proximity to mRNA vaccination are required.