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Thymoquinone (TQ) is one of the main phytochemical bioactive ingredients in Nigella sativa, with reported immunity-boosting properties. The current study evaluated the anti-inflammatory effect of TQ against inflammation brought on by free fatty acid Palmitate (PA) using macrophages raw 264.7 cell line. Data revealed that TQ significantly improved the viability of basal and PA stimulated Macrophages at concentrations of 50 and 100 μg/mL. Also, TQ significantly reduced nitric oxide and triglyceride levels in PA-stimulated macrophages at concentrations of 50 and 100 μg/mL. The pro-inflammatory cytokines studies revealed that PA significantly increased the release of the cytokines TNF-α, MHGB-1, IL-1β, and IL-6. TQ at concentrations 25, 50, and 100 μg/ml significantly decreases the release of the studied cytokines in PA-stimulated macrophages to variable extents with parallel inhibition to their corresponding gene expression. Bioenergetic assays showed that PA significantly decreased cellular ATP, mitochondrial complexes I and III activities and mitochondrial membrane potential with a subsequent significant increase in lactate production. At the same time, TQ can alleviate the effect of PA on macrophages' bioenergetics parameters to variable extent based on TQ concentration. To conclude, TQ could mitigate palmitate-induced inflammation and cytotoxicity in macrophages by improving macrophage viability and controlling cytokine release with improved PA-induced bioenergetics disruption. [Display omitted] • Thymoquinone significantly improved the viability of palmitate-treated macrophages. • Thymoquinone markedly reduced nitric oxide and triglyceride production in palmitate-treated macrophages. • Thymoquinone downregulates cytokines in palmitate-induced cytotoxicity in macrophages. • Thymoquinone counteracts the bioenergetic disruption caused by palmitate in macrophages. • Thymoquinone can open a new therapeutic avenue for managing fatty acids cytotoxicity-related metabolic disorders. [ABSTRACT FROM AUTHOR]

Purpose: Putative roles of long non-coding RNAs (lncRNAs) as indicators for diabetic retinopathy (DR) and associated complications are beginning to emerge. We aimed to evaluate a panel of circulating hyperglycemia-related lncRNAs: RNCR2, NEAT2, CDKN2B-AS1, and PVT1 in type 2 diabetes patients with/without DR and to correlate their levels with the clinical characteristics and response to aflibercept intravitreal injection in terms of visual acuity (VA) improvement, central macular thickness (CMT) decline, and macular edema resolution after 4 weeks of the initial injection. Methods: Pre-treatment plasma relative expression levels of the specified lncRNAs were quantified in 130 consecutive patients with diabetes (75 and 55 with/without DR, respectively) and 108 controls using quantitative real-time PCR. Results: One month after aflibercept injection, significant reductions in CMT and VA were observed in DR cohorts. The four lncRNAs were over-expressed in DM compared with those in controls. However, downregulated baseline plasma levels of RNCR2 and NEAT2 were observed in glycemic-controlled DR patients. None of the lncRNAs showed a correlation with the severity of retinopathy or drug response. Conclusion: Though circulating levels of the analyzed lncRNAs did not show an association with DR progression or aflibercept therapy response, the expression pattern demonstrated good diagnostic performance in differentiating DM from controls and DR. [ABSTRACT FROM AUTHOR]

Abstract Objective Identification of new molecular markers to enhance early diagnosis, prognosis and/or treatment of hepatocellular carcinoma (HCC) is a need. TOM34 (34 kDa-translocase of the outer mitochondrial membrane) protein expression deregulation has demonstrated to be involved in the growth of many cancers. Here, we aimed at evaluating serum TOM34 and some heat shock proteins (HSPA4 , HSPA1B , and HSP90AA1) expressions in hepatitis C virus (HCV)-related cirrhosis and HCV-induced HCC relative to controls and correlating these expressions to the clinicopathological data. Methods Serum specimens were collected from 90 patients with HCV associated complications (30 cirrhotic, 30 early HCC and 30 late HCC) and 60 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the four target genes using the Livak method. In silico network analysis was also executed to explore the contribution of the genes in liver cancer. Results The serum TOM34 and HSP90AA1 transcripts were significantly upregulated in HCC patients compared to cirrhotic ones with more up-regulation in late HCC patients. Receiver operating characteristic analysis showed the optimum cutoff value of 0.625 corresponding to 71.7% sensitivity and 56.7% specificity, and an area under the curve (AUC) of 0.705 to discriminate HCC from cirrhotic groups (P =.002). In multivariate analysis, ordination plot showed obvious demarcation between the study groups caused by the higher levels of TOM34 among other variables. Conclusions TOM34 and its partner HSP90AA1 might be used as a potential biomarker for monitoring HCV-induced HCC progression in the Egyptian population. Future large-scale validation studies are warranted. Highlights • HCC is associated with a significant TOM34 and its partner HSP90AA1 overexpression. • TOM34 monitoring could be a potential biomarker for early detection of HCC. • HSP90AA1 could be a good discriminator for late HCC. • Heat shock and chaperon genes showed sex-related differential expression. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. The oncogenic function of the long non-coding RNA; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HCC remains unclear. We aimed to evaluate MALAT1 serum expression profile in HCC and explore its relation to the clinicopathological features. Quantitative Real Time-Polymerase Chain Reaction was applied in 70 cohorts (30 HCC, 20 HCV, 20 controls). Further meta-analysis of clinical studies and in vitro validated experiments was employed. Serum MALAT1 showed area under the curve of 0.79 and 0.70 to distinguish patients with cancer from normal and cirrhotic individuals at fold change of 1.0 and 1.26, respectively. Expression level was significantly higher in males ( P <0.001) and patients with massive ascites ( P  = 0.005). Correlation analysis showed positive correlation of MALAT1 with total bilirubin (r = 0.456, P <0.001) and AST (r = 0.280, P  = 0.019), and negative correlation with the hemoglobin level (r = 0.312, P  = 0.009). Meta-analysis showed that the over-expressed MALAT1 was linked to tumor number [Cohen's d = 0.450, 95% CI (0.21 to 0.68)], clinical stage [Cohen's d = 0.048, 95% CI (-0.83 to 0.74)], and AFP level [Cohen's d = 0.354, 95% CI (0.1 to 0.57)]. In silico data analysis and systematic review confirmed MALAT1 oncogenic function in cancer development and progression. In conclusion, circulatory MALAT1 might represent a putative non-invasive prognostic biomarker indicating worse liver failure score in HCV-related HCC patients with traditional markers. Large-scale verification is warranted in future studies. [ABSTRACT FROM AUTHOR]

Prolongation of QT interval is possible with fluoroquinolones, yet the underlying contributing factors have not been elucidated. Two widely used fluoroquinolone drugs were at the focus of this study in rats with/without acute myocardial dysfunction (AMI) induced by isoproterenol. The effects of levofloxacin and ciprofloxacin on the cardiac mRNA expression of rat Kv4.3, Kv1.2 and Nav1.5 mRNAs were determined. Administration of the two antibiotics produced dose-dependent changes in ECG parameters that were more prominent in rats with AMI than healthy rats; this was accompanied by elevations in serum lactate dehydrogenase and creatine kinase-MB. Histopathological examination indicated some loss of striations, edema and fibrotic changes in rats with AMI; however the two antibiotics did not further exacerbate the cardiac histopathology. mRNA expression of the ion channels was altered in rats with AMI and healthy rats. In conclusion, long-term administration of levofloxacin and ciprofloxacin produced deleterious effects on the ECG pattern of rats with/without AMI. The effect was generally baseline-dependent and therefore, rats with AMI showed greater ECG disturbances and increases in cardiac enzymes. Taken together, these data make it advisable to monitor patients with a history of acute AMI requiring treatment with these antibiotics until data from human studies are available. [ABSTRACT FROM AUTHOR]

There is emerging evidence to support the role of microRNAs in allergic airway diseases and inflammation. Genetic variants in microRNA genes might affect microRNA-mediated cell regulation. This preliminary study was designed to investigate the association of the microRNA-196a2 rs11614913 (C/T) polymorphism with susceptibility to asthma and clinical outcomes in children and adolescents. Genotyping of rs11614913 polymorphism was determined in 96 patients with bronchial asthma (6-18 years of age) and 96 unrelated controls, using real-time polymerase chain reaction technology. In-silico target prediction and network core analyses were performed. The asthmatics did not show significant differences in genotype distribution ( p = 0.609) and allele frequencies ( p = 0.428) compared with the controls. There were also no associations with disease duration, age at onset, asthma phenotype, asthma control, therapeutic level, airway hyper-responsiveness, or biochemical parameters in the blood. However, the CC genotype was associated with a more severe degree of asthma ( p = 0. 023) and higher frequency of nocturnal asthma ( p = 0.002). Carriers for CC were 17 times more likely to develop nocturnal asthma, and had a more than 2.5-fold increased risk for poor disease outcome compared with CT and TT individuals. In conclusion, microRNA-196a2 rs11614913 polymorphism might be associated with asthma severity in our sample of the Egyptian population. Further investigations in studies with a larger sample size and functional tests are needed to validate our findings and to explore the detailed biological mechanisms. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is recognized as one of the leading causes of blindness worldwide. Searching and validation for a novel therapeutic strategy to prevent its progress are promising. This work aimed to assess the retinal protective effects of duloxetine (DLX) in Alloxan-induced diabetic mice model. Animals were equally and randomly divided to four groups (eight mice per group); group 1: is the control group, 2: diabetic group, 3&4: diabetic and after 9 weeks received DLX for 4 weeks (15 mg/kg and 30 mg/kg), respectively. Quantitative real-time PCR (qPCR) analysis revealed nerve growth factor (NGF), inducible nitric oxide synthase (iNOS) and transforming growth factor beta (TGF-β) genes upregulation in the diabetic group compared to controls. Also, increased retinal malondialdehyde (MDA) and the decline of reduced glutathione (GSH) levels were observed. The morphometric analysis of diabetic retina revealed a significant reduction in total retinal thickness compared to control. Diabetic retinal immunostaining and Western blot analyses displayed glial fibrillary acidic protein (GFAP) and vascular endothelial cell growth factor (VEGF) proteins expression upregulation as well as glucose transporter-1 (GLUT-1) downregulation comparing to controls. However, DLX-treated groups showed downregulated NGF , iNOS , and TGF-β that was more obviously seen in the DLX-30 mg/kg group than DLX-15 mg/kg group. Furthermore, these groups showed amelioration of the oxidative markers; MDA and GSH, retaining the total retinal thickness nearly to control, GFAP and VEGF downregulation, and GLUT-1 upregulation compared to diabetic group. Taken together, it could be summarized that duloxetine can attenuate DR via the anti-inflammatory and the anti-oxidative properties as well as modulating the angiogenic and the neurotrophic factors expressions. This could hopefully pave the road to be included in the novel list of the therapeutic regimen for DR after validation in the clinic. Image 1 • NGF , iNOS and TGF-β genes over-expression was observed in diabetic mice. • Diabetic retinal immunostaining displayed GFAP upregulation and GLUT-1 protein expression downregulation. • Increased malondialdehyde (MDA) levels and decline of reduced glutathione (GSH) levels were observed in diabetic retinae. • Western blot analysis of diabetic retina displayed upregulation of GFAP and VEGF, and downregulation of GLUT-1 expression. • Duloxetine can attenuate DR via the anti-inflammatory/anti-oxidative properties, and the neurotrophic factors modulation. [ABSTRACT FROM AUTHOR]

Background/objectives: Cystic fibrosis (CF) is a life-limiting genetic disorder affecting multiple organ systems. This study compared clinical outcomes, hospitalization rates, and survival between children and adolescents with CF who received CFTR modulator therapies (ivacaftor, lumacaftor, tezacaftor, and elexacaftor)., Methods: A retrospective cohort study was conducted using data from the TriNetX global collaborative network. Patients with CF aged 2-12 years (children) and 13-18 years (adolescents) who received CFTR modulator therapies were included. The propensity score matching balanced baseline characteristics between the two age groups., Results: After propensity score matching, 946 patients per group were analyzed. The incidence of respiratory failure (3.81% vs. 1.06%, p < 0.001) and respiratory infections (62.7% vs. 57.5%, p = 0.021) were significantly higher in adolescents compared to children. Adolescents had a higher risk of respiratory failure (HR = 3.6, 95% CI = 1.79-7.21, p < 0.001) and respiratory infections (HR = 1.09, 95% CI = 1.01-1.17, p < 0.001). Adolescents also had a higher hospitalization rate (29.6% vs. 20.3%, p < 0.001), with a 47% higher risk (HR = 1.47, 95% CI = 1.22-1.77, p = 0.001), more hospital visits per person (8.8 vs. 3.7, p = 0.004), and longer hospital stays (32.7 vs. 20.4 days, p = 0.006). Mortality rates were similar between the groups (1.58% vs. 1.26%, p = 0.56)., Conclusions: CF patients who initiated CFTR modulator therapies during adolescence had a higher incidence of respiratory failure, respiratory infections, hospitalization rates, and healthcare resource utilization compared to those who started therapy in childhood, despite similar mortality rates. These findings highlight the importance of the early initiation of CFTR modulator therapies.

Background: Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation., Methods: This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival., Results: Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%-0.7% and 1.5%-0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone., Conclusion: Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.

Background/objectives: Pediatric populations with well-differentiated thyroid cancer typically have favorable prognoses. However, the role of radioactive iodine (RAI) ablation in these patients remains uncertain. This investigation evaluates the national trends, therapeutic practices, and the impact of RAI on clinical outcomes., Methods: Patients aged 21 years or younger with differentiated thyroid cancer, identified from the SEER database between 2000 and 2019, were analyzed. We compared the treatment approaches and survival outcomes of patients who underwent RAI ablation with those who did not., Results: This retrospective cohort study encompassed 5318 pediatric patients, with 55.9% ( n = 2973) who underwent RAI ablation. RAI utilization declined from 65% to 38.4% in 2019. Compared with those who did not undergo RAI, RAI patients presented with a larger tumor size (mean size: 27.7 vs. 20.4 mm), a higher T3/T4 stage (35.8% vs. 15.3%), nodal metastases (60.7% vs. 28.8%), and distant metastases (2.7% vs. 0.9%) (all p < 0.001). Despite this, RAI was not an independent predictor of recurrence, second malignancy, or mortality. The analysis showed no significant differences in long-term survival between the RAI and non-RAI groups ( p > 0.05), with African American patients having an increased risk of mortality (HR = 3.81; p = 0.038). Cancer-directed surgery emerged as a protective factor (HR = 0.08; p = 0.018), while RAI treatment did not significantly affect mortality risk ( p = 0.09)., Conclusions: Excellent pediatric thyroid cancer outcomes were achieved regardless of RAI use. Further research should clarify appropriate RAI indications while addressing racial outcome inequities.

Diabetic nephropathy (DN) affects about one-third of patients with diabetes and can lead to end-stage renal disease despite numerous trials aimed at improving diabetic management. Non-coding RNAs (ncRNAs) represent a new frontier in DN research, as increasing evidence suggests their involvement in the occurrence and progression of DN. A growing body of evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in DN signaling pathways might serve as novel biomarkers or therapeutic targets, although this remains to be fully explored. Our study included four groups, each comprising 40 adults: patients with diabetes (a) without albuminuria, (b) with microalbuminuria, (c) with macroalbuminuria, and a control group. All participants underwent history-taking and clinicolaboratory assessments, including CBC, fasting blood sugar, HbA1c, lipid profile, liver function, and renal function tests. Additionally, expressions of lncRNA H19, miRNA-29b, PI3K, AKT, mTOR, and HIF-1 alpha were assessed using qPCR. lncRNA H19 expression was upregulated in patients with albuminuria compared to the DM group. Furthermore, based on qPCR, the level of lncRNA H19 was negatively correlated with eGFR and miRNA-29b expression. On the other hand, the lncRNA H19 level was positively correlated with PI3K, AKT, mTOR, and HIF-1 alpha levels. We also found that the lncH19/miRNA-29b ratio was significantly increased in patients with DN and macroalbuminuria. In conclusion, lncRNA H19 was upregulated in patients with DN, and this increase was associated with miRNA29b downregulation. Therefore, our study suggests a novel link between the lncH19/miRNA-29b ratio and DN, indicating that it might serve as a potential biomarker for the dynamic monitoring of DN.

Background/Objectives : Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus, posing significant health. While global studies have indicated a concerning lack of awareness regarding DKA among patients with diabetes, research specific to the northern area of Saudi Arabia remains limited. This study aims to explore the level of knowledge and awareness of DKA among patients with diabetes residing in the local region. Methods : A cross-sectional analysis was conducted utilizing a non-probability convenient sampling technique, with 339 participants recruited from March to August 2024. Data were gathered through a self-administered pre-validated questionnaire distributed via different social media platforms to assess demographic characteristics and awareness levels relating to DKA, including knowledge of its symptoms, causes, and treatment options. Results : Although there was moderate awareness of DKA, with 68.4% having heard of the condition, two-thirds of the participants exhibited significant gaps in overall knowledge. Among those aware, 76.3% recognized DKA as an emergency requiring immediate medical intervention. At the same time, 64.6% understood the causes of DKA, and only 25.6% identified insulin deficiency as a major contributing factor. Although 62.5% felt knowledgeable about treatment, 66.0% incorrectly identified oral sugar as a DKA treatment. Notably, 30.1% cited social media as their main information source. Age emerged as an essential factor impacting knowledge, with younger participants (ages 18-30) demonstrating higher awareness than older individuals. Additionally, single participants displayed a higher percentage of good knowledge than married participants ( p = 0.000). Non-working individuals showed better overall knowledge about DKA ( p = 0.002). The duration of diabetes did not show a significant association with knowledge levels about DKA across the various duration categories. Conclusions : The present findings underscore a substantial knowledge gap concerning DKA among the local community, highlighting a critical need for targeted public health educational interventions.

Purpose: Clear patient communication with the physician is an integral aspect of cancer treatment and successful health outcomes. Previous research has shown improved cancer screening in cases of patient navigator assistance to limited English proficient patients, but no research has analyzed the relationship between language isolation and cancer incidence rates in the United States., Methods: Using state-level data from the United States Census Bureau and the National Cancer Institute, we analyzed the correlations between language isolation and age-adjusted incidence rates across 19 different invasive cancers., Results: A complex relationship between language isolation and cancer incidence rates was found. States such as California, New York, Texas, and New Jersey show high language isolate prevalence and elevated cancer incidence rates. Cancer subtype incidence rates varied between states, indicating the multifactorial importance of lifestyle, genetics, and environment in cancer. California had the highest language isolation ranking of 8.5% and elevated rates of ovarian (10.4/100,000) and stomach (9.1/100,000) cancers. New York, with the second-highest language isolation ranking of 7.6%, manifests a pronounced prevalence of ovarian (11.3/100,000) and stomach (10.9/100,000) cancers. Overall, positive correlations were observed between language isolation and ovarian/stomach cancers, while negative correlations were found with lung, kidney, melanoma, and colorectal cancers., Conclusion: This study emphasizes the need to address language barriers and other social determinants of health in cancer prevention/control. Targeted interventions, such as culturally appropriate education, increased access to linguistically and culturally appropriate cancer screening, and language lessons, are crucial in improving health outcomes in linguistically diverse communities., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The ethical review and approval were waived for this study. Data were retrieved from “SEER Research Data” upon request, and the data agreement form was signed through Dr. Toraih (SEER ID: 15332-Nov2019). Patient consent: Patient consent was waived since it was retrieved from the public database “SEER Research Data.”, (© 2024. The Author(s).)

Objectives: Hepatotoxicity is a severe outcome of methotrexate (MTX) therapy, limiting its clinical use and contributing to its related morbidity and mortality. This study investigated the hepatoprotective effects of nitazoxanide (NTZ), an antiprotozoal drug, against MTX-induced hepatotoxicity and whether endoplasmic reticulum (ER) stress-modulation underlies the expected beneficial effects of NTZ., Methods: Thirty-six rats were allocated to six groups, one control group and five MTX groups, where induction of hepatotoxicity was achieved via injecting MTX (20 mg/kg). Groups were assigned as MTX-vehicle, NTZ-100, and NTZ-200 groups (at 100 and 200 mg/kg/day, gavage, respectively), N-acetyl cysteine (NAC) group (500 mg/kg), and 4-phenyl butyric acid (4-PBA) group (150 mg/kg, i.p). Liver function enzymes in serum, hepatic oxidative stress, proinflammatory cytokines, apoptosis, and ER-stress biomarkers were assessed. A histopathological examination was performed., Results: Treatment with NTZ lessened the serum liver enzymes, reduced malondialdehyde (lipid peroxidation product), enhanced antioxidant capacity, attenuated proinflammatory cytokines, and suppressed apoptosis. The protective effect of NTZ was dose-dependent, and the findings observed with the high-dose NTZ were similar to those obtained with the ER-stress inhibitor (4-PBA)., Conclusion: NTZ exerted a hepatoprotective effect in MTX-challenged rats that is mediated via modulation of ER stress and inhibiting apoptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mahmoud, Elshazly, El-shaarawy, Zaitone, Aldahish, Ahmed, Fawzy, Aloyouni, Abed, Saeedi and El-Sayed.)

Background: Activating mutations in the BRAF oncogene occur in 45% of papillary thyroid carcinomas (PTCs). Though less studied, K601E may identify a clinically distinct subset of thyroid neoplasms., Methods: A bioinformatics assessment was conducted using the COSMIC database and in silico data analysis. A systematic search was conducted through August 2024 to identify studies reporting BRAF mutation in thyroid neoplasms. Pooled prevalence, histopathological subtype distribution, extrathyroidal extension, lymph node metastasis, recurrence, and survival were extracted/analyzed from 32 studies (13 191 patients)., Results: In the COSMIC database, BRAF K601E was found in various tissue types but mainly in the thyroid. In silico data analysis revealed a structural and functional basis for differences between K601E and V600E. Upon systematic review, the BRAF K601E mutation was identified in 2.8% of PTCs compared to 22% with V600E. The stratified analysis revealed geographical differences, with higher rates in Italy (5.23%) and the United States of America (3.31%). The K601E mutant was enriched for follicular-patterned variants like NIFTP (11.2% of cases). Meta-analysis demonstrated significantly reduced extrathyroidal extension for K601E versus V600E mutants (RR = 0.22, 95% CI = 0.10-0.50, p = 0.0003)., Conclusion: K601E-mutated neoplasms could be a unique clinicopathological entity associated with low-risk histology and reduced extrathyroidal extension, consistent with a more indolent course than V600E mutants. Although detecting K601E may potentially guide conservative management, further prospective studies are needed., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Purpose: Income inequality profoundly impacts cancer outcomes, yet its specific effects on thyroid cancer remain unclear. Elucidating the influence of socioeconomic disparities is imperative to advance health equity and optimize patient care. This study evaluates associations between median household income and thyroid cancer recurrence and survival using national cancer registry data., Methods: 139,302 thyroid cancer patients undergoing surgery from 2000 to 2019 were analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized by median annual household income at the county level (> or <$75,000). Multivariable regression determined the impact of income on recurrence and overall mortality., Results: Higher-income patients had 26 % lower recurrence odds (OR 0.74, 95 %CI 0.55-0.99, p=0.042) and longer median survival (18.1 vs 17.7 years, p<0.001) compared to lower-income patients. On multivariate analysis, high income remained an independent predictor of reduced mortality after adjusting for demographics, tumor factors, and treatment (adjusted HR=0.84, 95 %CI=0.81-0.87, p<0.001). Cancer-directed surgery (HR=0.28, 95 %CI=0.26-0.30, p<0.001) and radioactive iodine (HR=0.69, 95 %CI=0.66-0.71, p<0.001) were associated with lower mortality risk., Conclusions: Income disparities have a significant influence on thyroid cancer outcomes, including lower recurrence and reduced mortality. Targeting socioeconomic inequity could substantially reduce recurrence, improve survival, and promote health equity for all patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/Objectives: Numerous national programs have been launched to enhance public health in Saudi Arabia, primarily aiming to promote healthy lifestyles through regular physical activity and a balanced diet. However, there is a lack of studies assessing the effectiveness and utilization of these initiatives. This study aimed to evaluate the perceived effectiveness and utilization of health promotion initiatives and identify the associated factors. Methods: A population-based cross-sectional study was conducted among adults (aged > 18 years) in Saudi Arabia using an online questionnaire through a convenient sampling approach. The questionnaire comprised three sections: sociodemographic data, medical history, and health promotion initiatives. An adjusted analysis was conducted using ordinary least squares (OLS) regression. Results: A total of 999 participants completed the survey. Walking paths emerged as the most perceived effective initiative, while labeled caloric menus were the most utilized. Perceptions of walking paths varied by age and health status; individuals aged 25-44 and lower-income groups viewed them less favorably. In contrast, those in good health found them more effective. Perceptions of calorie-related information on menus differed according to health status. Saudis perceived taxes on soft drinks less favorably than non-Saudis. Regionally, the western region favored fresh juice options compared to the East. The utilization of walking paths was higher among married individuals and those without chronic conditions, while the consumption of soft drinks was significant among younger and extremely obese individuals. Conclusions: The study revealed diverse perceptions and utilization patterns regarding health promotion initiatives among various demographic and socioeconomic groups, emphasizing the need for tailored strategies to enhance their effectiveness across populations.

Rotenone is a pesticide that causes complex I inhibition and is widely known to induce motor disability and experimental Parkinson's disease (PD) in rodents. Evidence suggests a crucial role for sirtuin/nuclear factor-kappaB/nod-like receptor family, pyrin domain-containing 3 (SIRT1/NFκB/NLRP3) signaling and inflammation in PD and rotenone neurotoxicity. Hesperetin (C16H14O6) is a citrus flavonoid with documented anti-inflammatory activity. We investigated the value of hesperetin in delaying rotenone-induced PD in mice and the possible modulation of inflammatory burden. PD was induced in mice via rotenone injections. Groups were assigned as a vehicle, PD, or PD + hesperetin (50 or 100 mg/kg) and compared for the motor function, protein level (by ELISA), and gene expression (by real-time PCR) of the target proteins, histopathology, and immunohistochemistry for tyrosine hydroxylase enzyme. Hesperetin (50 or 100 mg/kg) alleviated the motor disability and the striatal dopamine level and decreased the expression of NLRP3 and NF-κB but increased SIRT1 expression ( p  < 0.05). Further, it enhanced the neural viability and significantly decreased neural degeneration in the substantia nigra, hippocampus, and cerebral cortex ( p  < 0.05). Taken together, we propose that hesperetin mediates its neuroprotective function via alleviating modulation of the SIRT1/NFκB/NLRP3 pathway. Therefore, hesperetin might delay the PD progression.

Background/Objectives: One of the most abundant and growing neurodevelopmental disorders in recent decades is attention deficit hyperactivity disorder (ADHD). Many trials have been performed on using drugs for the improvement of ADHD signs. This study aimed to detect the possible interaction of naringin with Wnt/β-catenin signaling and its putative anti-inflammatory and protective effects in the mouse ADHD model based on bioinformatic, behavioral, and molecular investigations. Furthermore, molecular docking was applied to investigate possible interactions with the GSK-3β and HSP90 proteins. Methods : Male Swiss albino mice were divided into four groups, a normal control group, monosodium glutamate (SGL) control, SGL + naringin 50 mg/kg, and SGL + naringin 100 mg/kg. The psychomotor activity of the mice was assessed using the self-grooming test, rope crawling test, and attentional set-shifting task (ASST). In addition, biochemical analyses were performed using brain samples. Results : The results of the SGL group showed prolonged grooming time (2.47-folds), a lower percentage of mice with successful crawling on the rope (only 16.6%), and a higher number of trials for compound discrimination testing in the ASST (12.83 ± 2.04 trials versus 5.5 ± 1.88 trials in the normal group). Treatment with naringin (50 or 100 mg per kg) produced significant shortening in the grooming time (31% and 27% reductions), as well as a higher percentage of mice succeeding in crawling with the rope (50% and 83%, respectively). Moreover, the ELISA assays indicated decreased dopamine levels (0.36-fold) and increased TNF-α (2.85-fold) in the SGL control group compared to the normal mice, but an improvement in dopamine level was observed in the naringin (50 or 100 mg per kg)-treated groups (1.58-fold and 1.97-fold). Similarly, the PCR test showed significant declines in the expression of the Wnt (0.36), and β-catenin (0.33) genes, but increased caspase-3 (3.54-fold) and BAX (5.36-fold) genes in the SGL group; all these parameters were improved in the naringin 50 or 100 mg/kg groups. Furthermore, molecular docking indicated possible inhibition for HSP90 and GSK-3β. Conclusions : Overall, we can conclude that naringin is a promising agent for alleviating ADHD symptoms, and further investigations are required to elucidate its mechanism of action.

Recognizing pediatric eye health issues at an early stage, along with ensuring that parents are well informed, is crucial. This study measures parents' knowledge and perspectives on pediatric ophthalmic disease. The study utilized a cross-sectional design, and participants included Saudi parents of children residing in Saudi Arabia. Data were collected using a pre-validated self-administered questionnaire with a scoring system. Sociodemographic characteristics and factors associated with knowledge/attitude were collected and analyzed. Initially, 425 respondents participated in this study. Excluding the participants whose work was related to healthcare and those with incomplete data yielded 370 responses on which the subsequent analyses were performed. The analysis revealed that only half of the parents recognized the need for annual eye examinations for children. Most of them showed gaps in knowledge regarding the frequency of routine eye exams and indicators of visual problems. Notably, parents with good/excellent knowledge were more proactive in their eye care practices, such as adherence to recommended eye examination schedules and accepting corrective measures like glasses for common conditions such as refractive errors and amblyopia. However, parental willingness to permit surgical interventions did not correlate significantly with their level of knowledge, signaling the influence of other factors. In conclusion, this study underscores the need for enhanced public health education to improve parental awareness of pediatric eye diseases in Saudi Arabia. Given the link between knowledge and proactive eye health practices, targeted interventions should distribute comprehensive, culturally sensitive information accessible to all demographics.

Background and Objectives : The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods : We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results : In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443-0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189-1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions : While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression and play critical roles in tumorigenesis. Genetic variants in miRNA processing genes, DROSHA and DICER , have been implicated in cancer susceptibility and progression in various populations. However, their role in Egyptian patients with breast cancer (BC) remains unexplored. This study aims to investigate the association of DROSHA rs10719 and DICER rs3742330 polymorphisms with BC risk and clinical outcomes. This case-control study included 209 BC patients and 106 healthy controls. Genotyping was performed using TaqMan assays in blood, tumor tissue, and adjacent non-cancerous tissue samples. Associations were analyzed using logistic regression and Fisher's exact test. The DROSHA rs10719 AA genotype was associated with a 3.2-fold increased risk (95%CI = 1.23-9.36, p < 0.001), and the DICER rs3742330 GG genotype was associated with a 3.51-fold increased risk (95%CI = 1.5-8.25, p = 0.001) of BC. Minor allele frequencies were 0.42 for rs10719 A and 0.37 for rs3742330 G alleles. The risk alleles were significantly more prevalent in tumor tissue than adjacent normal tissue (rs10719 A: 40.8% vs. 0%; rs3742330 G: 42.7% vs. 0%; p < 0.001). However, no significant associations were observed with clinicopathological features or survival outcomes over a median follow-up of 17 months. In conclusion, DROSHA rs10719 and DICER rs3742330 polymorphisms are associated with increased BC risk and more prevalent in tumor tissue among our cohort, suggesting a potential role in miRNA dysregulation during breast tumorigenesis. These findings highlight the importance of miRNA processing gene variants in BC susceptibility and warrant further validation in larger cohorts and different ethnic populations.

Cadmium (Cd) and lead (Pb) are heavy metals (HMs) that persistently contaminate the ecosystem, and bioaccumulation in bones is a health concern. We used biochemical and molecular assays to assess the cytoprotective effect of vitamin D (VD) on Cd- and Pd-induced chemical toxicity of human bone osteoblasts in vitro. Exposing Cd and Pb to human osteoblast cultures at concentrations of 0.1-1000 µM for 24-72 h significantly reduced osteoblast viability in an exposure time- and concentration-dependent manner. The cytotoxic effect of Cd on osteoblasts was more severe than Pb's, with 72-h exposure estimated half maximal effective concentration (EC50) of 8 and 12 µM, respectively, and VD (1 and 10 nM) alleviated cytotoxicity. Bioenergetics assays of ATP, mitochondrial membrane potential, and mitochondrial complex I and III activity showed that both Cd and Pb (1 and 10 µM) inhibited cellular bioenergetics after 72-h exposure. Cd and Pb increased lipid peroxidation and reactive oxygen species with reduced catalase/superoxide dismutase antioxidant activities and increased activity of caspases -3, -8, and -9. Co-treatment with VD (1 and 10 nM) counteracted bioenergetic disruption, oxidative damage, and apoptosis in a concentration-dependent manner. These findings suggest that VD is effective in managing the toxic effects of environmental pollutants and in treating bone diseases characterized by oxidative stress, apoptosis, and bioenergetic disruption., (© 2024. The Author(s).)

Aim: To evaluate the impact of the COVID-19 lockdown on sleep patterns and quality among nursing students in our college., Design: A cross-sectional study was carried out., Methods: A total of 302 nursing students aged 18-25 years, representing both genders and various academic levels, participated in this study. A pre-validated, self-administered questionnaire was used to assess sleep quality during COVID-19 and it was distributed through various social media platforms for data collection., Results: Female students comprised the majority (92.1%) of participants. Of 332 nursing students, 302 completed the questionnaire, yielding a 91% response rate. Statistically significant differences were observed before and during the COVID-19 lockdown regarding the need to sleep after waking, feeling refreshed upon waking, satisfaction with individual sleep patterns and experiencing restless and troubled sleep (p = 0.001). Additionally, approximately one-third of nursing students (32.9%) reported poor sleep quality during the COVID-19 pandemic, with minimal impact on the total sleep hours among the studied cohorts., Public Contribution: The COVID-19 pandemic has statistically significant impacted nursing students' sleep quality and levels. Acknowledging these challenges and planning for providing supporting measurements is essential to ensuring that nursing students can maintain their physical and mental health, which is critical for their ability to provide quality healthcare., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively ( p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 ( p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 ( p = 0.015), and for men, it had an AUC of 0.792 ( p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

Background/Objectives: The effect of glucagon-like peptide-1 receptor (GLP-1R) agonists on calcium homeostasis is poorly understood. This study aimed to investigate the association between GLP-1R agonist use and the risk of hypocalcemia and/or hypercalcemia, as well as other clinical outcomes. Methods: A retrospective cohort study used de-identified patient data from the TriNetX Global Collaborative Network, including 15,655 adult patients prescribed GLP-1R agonists and 15,655 propensity-matched controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Results: GLP-1R agonist use was associated with a reduced risk of hypocalcemia (2.7% vs. 5.5%, RR 0.49, 95% CI: 0.44-0.55) but an increased risk of hypercalcemia (2.3% vs. 1.1%, RR 2.02, 95% CI: 1.69-2.42). The effect on hypocalcemia was most pronounced during the first six months of treatment. Among individual agents, tirzepatide showed the most pronounced effect, reducing hypocalcemia risk by 63% while increasing hypercalcemia risk by 85%. Semaglutide demonstrated similar effects, while dulaglutide and liraglutide showed modest effects. Furthermore, GLP-1R agonist use was associated with reduced risks of emergency visits (RR 0.57, 95% CI: 0.54-0.60), hospitalizations (RR 0.40, 95% CI: 0.36-0.44), cardiovascular events, and all-cause mortality (HR 0.27, 95% CI: 0.21-0.36). Conclusions : GLP-1R agonists exhibit a complex influence on calcium homeostasis, reducing hypocalcemia risk while increasing hypercalcemia risk. Beyond calcium regulation, these medications significantly reduce healthcare utilization, improve cardiovascular outcomes, and decrease mortality. Further research is needed to elucidate the mechanisms behind the differential effects of individual GLP-1R agonists, particularly tirzepatide, to optimize personalized treatment approaches and long-term safety.

Background and Objective: The interwoven immunological, biological, and genetic complexity of thyroid diseases makes suitable targeted therapies particularly challenging to develop. Stemming from ancient practices, al-hijamah, or wet cupping, has achieved notable popularity in recent years, leading to unique applications in modern medicine. By grappling with the current literature that links the effects of wet cupping with the immune system in patients with Hashimoto's thyroiditis (HT), this narrative review aims to compose a comprehensive assessment of this adjunctive treatment based on evidence of its integration into practice., Methods: Between upregulating critical players of the innate immune system, such as immunostimulatory cytokines, white blood cells (WBCs) and natural killer (NK) cells, and downregulating essential thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) and inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), wet cupping practices provide promising complementary therapy for hypothyroidism., Key Content and Findings: Wet cupping manipulates in vivo molecular mechanisms, as outlined in hemodynamic and microparticle clearance theories, to slow disease progression and even development in disease-free populations. Given the established utilization of wet cupping in the context of autoimmune diseases and inflammatory conditions, the emerging utility of wet cupping continues to gain credibility., Conclusions: This literature review illuminates the documented improvements in immune and biological function due to cupping therapeutic practices and sheds light on its appropriate application in the clinical setting for patients with HT. Furthermore, this review proposes a clear need for implementing future clinical trials, which may effectively bridge pathophysiological causes of hypothyroidism with underrated techniques for enhanced thyroid health., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-173/coif). E.K. serves as an Editor-in-Chief of Gland Surgery from May 2024 to April 2026. The other authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Background: Self-medication among university students is becoming a health concern, especially during examinations and stress. This pattern of medication use among students could lead to adverse health consequences if it is not addressed and tackled. Thus, this study investigated the most associated factors with this practice among students., Methods: An observational cross-sectional study was conducted among university students in Northern Borders Province, Saudi Arabia. A total of 220 students were selected and took part in the survey. Data was collected through a self-administered questionnaire. The survey was distributed among participants to answer five sections: demographic and socioeconomic characteristics, health status problems, satisfaction with academic performance, and self-medication questions. The content validity was tested using a pilot sample of 30 students. The descriptive, univariate, and multivariate analyses were conducted using the Statistical Package for Social Science program., Results: In the present sample of university students, the response rate was 100%. Approximately one-third reported using medications without prescriptions, and 83% of them have used medications three times at most during the past 12 months. Headache was the most common reason for use (59%), followed by fever (20%). Adjusted multivariate analysis showed that students who were 21-24 years of age (OR = 3.79, 95% CI = 1.21-11.82), female (OR = 2.43, 95% CI = 1.03-5.72), and living alone in private housing (OR = 3.62, 95% CI = 1.32-9.90) were at high risk of self-medication as compared to their counterparts. However, students in the last years of college (fourth (OR = 0.14, 95% CI = 0.03-0.62), fifth (OR = 0.21, 95% CI = 0.05-0.95), sixth (OR = 0.05, 95% CI = 0.01-0.35)) were at lower risk as compared to their counterparts., Conclusion: The study found that self-medication was common among university students, with higher rates among those who were 21-24 years old, female, and living alone in private housing, but lower rates among students in the later years of college. Educational programs and awareness campaigns should target students who are at higher risk of practicing self-medication to avoid misuse of over-the-counter medications., Competing Interests: “The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”, (© 2024 The Authors. Published by Elsevier Inc.)

Background: Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer with limited treatment options for advanced disease. A small subset exhibits mixed MTC histology with both medullary and well-differentiated components. We investigated survival outcomes with systemic therapy in isolated versus mixed MTC using a large population-based cohort., Methods: Patients diagnosed with MTC from 2000 to 2019 were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The overall and thyroid cancer-specific survivals were compared between isolated (n = 1814) and mixed (n = 113) MTC cohorts. The impact of postoperative systemic therapy on survival was analyzed., Results: No significant difference in 10-year overall survival was observed between isolated (77.4 %) and mixed (75.2 %) MTC in a cohort of 1927 patients. Median overall survival was similar between isolated (136.9 months) and mixed MTC (129.0 months), p  = 0.81. While systemic therapy improved 10-year survival in isolated MTC (83.2 % vs. 76.9 %, p  < 0.001), no benefit was seen in mixed MTC (76.4 % vs. 74.2 %, p  = 0.82). Multivariate analysis confirmed survival gains with systemic therapy for isolated (HR = 0.763, 95%CI = 0.590-0.987, p  = 0.040) but not mixed MTC (HR = 0.909, 95%CI = 0.268-3.079, p  = 0.88)., Conclusions: In this large population-based study, no significant survival difference was observed between isolated and mixed MTC. Systemic therapy was associated with improved survival in isolated MTC, but not in the mixed subtype. These findings suggest a differential treatment response that warrants further investigation in prospective studies and may inform histology-tailored management strategies for mixed MTC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Several single nucleotide polymorphisms (SNPs) in multiple interleukin receptor genes could be associated with asthma risk and/or phenotype. Interleukin-17 (IL-17) has been implicated in tissue inflammation and autoimmune diseases. As no previous studies have uncovered the potential role of IL17 receptor A ( RA ) gene variants in asthma risk, we aimed to explore the association of four IL17RA SNPs (i.e., rs4819554A/G, rs879577C/T, rs41323645G/A, and rs4819555C/T) with asthma susceptibility/phenotype in our region. TaqMan allelic discrimination analysis was used to genotype 192 individuals. We found that the rs4819554 G/G genotype significantly reduced disease risk in the codominant (OR = 0.15, 95%CI = 0.05-0.45, p < 0.001), dominant (OR = 0.49, 95%CI = 0.26-0.93, p = 0.028), and recessive (OR = 0.18, 95%CI = 0.07-0.52, p < 0.001) models. Similarly, rs879577 showed reduced disease risk associated with the T allele across all genetic models. However, the A allele of rs41323645 was associated with increased disease risk in all models. The G/A and A/A genotypes have higher ORs of 2.47 (95%CI = 1.19-5.14) and 3.86 (95%CI = 1.62-9.18), respectively. Similar trends are observed in the dominant 2.89 (95%CI = 1.47-5.68, p = 0.002) and recessive 2.34 (95%CI = 1.10-4.98, p = 0.025) models. For the rs4819555 variant, although there was no significant association identified under any models, carriers of the rs4819554*A demonstrated an association with a positive family history of asthma (71.4% in carriers vs. 27% in non-carriers; p = 0.025) and the use of relievers for >2 weeks (52.2% of carriers vs. 28.8% of non-carriers; p = 0.047). Meanwhile, the rs4819555*C carriers displayed a significant divergence in the asthma phenotype, specifically atopic asthma (83.3% vs. 61.1%; p = 0.007), showed a higher prevalence of chest tightness (88.9% vs. 61.5%; p = 0.029), and were more likely to report comorbidities (57.7% vs. 16.7%, p = 0.003). The most frequent haplotype in the asthma group was ACAC, with a frequency of 22.87% vs. 1.36% in the controls ( p < 0.001). In conclusion, the studied IL17RA variants could be essential in asthma susceptibility and phenotype in children and adolescents.

Background Breast cancer remains a significant public health issue globally and is notably pervasive within the female population, representing a leading cause of concern. It poses a challenge across different age groups and is influenced by diverse risk factors that include genetic predispositions and various elements of lifestyle. Saudi Arabia, mirroring the global situation, has also seen its share of this disease's impact, prompting a closer look at the factors contributing to its prevalence. Educating the public and advocating for lifestyle changes are crucial steps in cancer prevention. With early-stage diagnosis and screening, many lives can potentially be saved. Our research is focused on understanding the level of awareness and preventative practices among women in the Northern Border region of Saudi Arabia. It seeks to explore the influence of familial history on knowledge and perceptions surrounding breast cancer, which could guide future educational and screening programs. Methods This cross-sectional study engaged 643 female participants, aged 18 and above, from the Northern Border region of Saudi Arabia upon their informed consent. Data were compiled via a structured questionnaire encompassing sociodemographic information, breast cancer knowledge, and preventive practices. Results The data disclosed that a significant majority (86%) recognized breast lumps as indicative of breast cancer, with 69.1% cognizant of hereditary risks. Awareness about lactation as a preventative strategy was noted in 76.7% of the participants, followed by 70.6% acknowledging the merits of a healthy diet. The study unveiled no substantial awareness disparity between individuals with or without a family history of the disease. Alarmingly, 80.4% had never sought a breast examination, and a parallel 83.7% had not undergone mammography. Conclusion The study sheds light on the heterogeneity in breast cancer awareness among women in Saudi Arabia's Northern Border region. Although the recognition of lumps and the preventative role of lactation is relatively high, there remains a deficit in comprehending additional symptoms, signs, and risk factors. The conspicuously low rates of breast cancer examinations and mammography underscore an urgent need for enhanced educational initiatives and a strategic push toward bolstering participation in regular cancer screenings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alanazi et al.)

Introduction Smartphones are widely utilized by individuals on a daily basis for a variety of activities, including communication, web browsing, and gaming. However, the excessive and prolonged use of these devices often leads to adverse effects on musculoskeletal health. This study aimed to assess the effect of mobile phone use on musculoskeletal complaints among nursing students at Northern Border University. Methods An analytical descriptive study was conducted using a convenience sample of 202 nursing students recruited via a Google survey questionnaire. The questionnaire comprised four sections concerning the students' demographics, smartphone data collection tools, the Smartphone Addiction Scale (SAS-SV), and the Nordic Musculoskeletal Questionnaire (NMQ). Results Among the study participants, 62.6% were females, with 52.4% spending more than 5 hours daily on media and technology usage, often extending into bedtime. In the last 12 months, neck pain was the most prevalent complaint, reported by 38.8% of the participants, followed by shoulder pain experienced by 20.3% of the sample. Notably, female students displayed a significantly higher incidence of musculoskeletal pain, with rates as high as 81.7% showing statistical significance (p<0.001). A significant association was also observed between mobile phone addiction and academic grade, as well as the time spent on media and technology usage daily (p<0.001). Conclusions There is a significant association between mobile phone use and discomfort in the musculoskeletal system, particularly in the neck region. Moreover, female students tend to experience more pronounced musculoskeletal discomfort compared to their male counterparts. The study also suggests that extended usage of mobile phones, especially at bedtime, increases the likelihood of experiencing musculoskeletal discomfort., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Mersal et al.)

Clinical training plays a fundamental role in nursing students' acquisition of professional capabilities. This study aimed to explore the perceived challenges nursing students face during clinical training. An explorative cross-sectional study was applied. A proportionate, stratified, random sample was enrolled in the study with inclusive criteria, including nursing students (2nd - 4th year) and interns who attended their internship in regional hospitals. A validated electronic questionnaire was used for data collection, which consisted of three sections and 29 items. The section that focused on the difficulties experienced by nursing students during their practical training included six elements: teachers, healthcare professionals, the students themselves, tasks, time management, and the location of the training. Another section inquired about the students' perspectives on the benefits of clinical training. A three-point "Likert scale" was applied. The findings indicated that mild (24%), moderate (62%), and severe (14%) degree of challenges were perceived by the study participants. The mean score for the total challenges during clinical training was 2.00 ± 0.28, and there were variations in the perceived challenges among grade levels. In conclusion, there are variations in the perceived challenges during clinical training among different grade levels. These challenges were related to teachers, health workers, the students, tasks, the time, and the place. Enhancing the nursing curricula alignment with practical training objectives is recommended, focusing on the development of technical and interpersonal skills with appropriate guidance, alongside positive clinical settings to help nursing students learn and boost their confidence in their approach., Competing Interests: Conflict of Interest: The authors declare no conflict of interest., (© 2024 the Author(s), licensee AIMS Press.)

Background: The Omicron variant (B.1.1.529 lineage) of SARS-CoV-2 represents a substantial global health challenge due to its high transmissibility and potential resistance to immunity from vaccines or previous infections. Among the rapidly evolving Omicron lineages, the BA.2.75 and the emerging CH.1.1 have garnered attention. While BA.2.75 is marked by mutations that may enhance immune evasion, CH.1.1 is distinguished by the S: L452R mutation, linked to increased pathogenicity and transmission. Initially identified in India by the end of 2021, these variants have exhibited global dissemination, signaling an urgent need to track and analyze their progression., Methods: In this study, the genomic and geographical distribution data of CH.1.1 were collected from the Global Initiative on Sharing Avian Influenza Data (GISAID), PANGOLIN, CoV-Spectrum, and NextStrain databases. Due to the unavailability of epidemiological and genomic data of the CH.1.1 lineage, PubMed and ScienceDirect were used as sources of the phenotypic data of the lineage variations. Amino acid variations utilized in the data mining included S: R346T, S: K444T, S: L452R, and S: F486S., Results: The current epidemiological data indicate that CH.1.1 is more likely to become one of the dominant spreading lineages in the United Kingdom, New Zealand, Australia, and the United States based on a 32% growth advantage, present CH.1.1 lineage cases number, and the amino acid variation's impact., Conclusion: A significant increase in the newly detected lineage CH.1.1 is highly anticipated. The rise in the detected sequences number from 13,231 on January 21, 2023, to 23,181 on February 6, 2023, supports the prediction and growth advantage of the lineage detected cases. Increases in viral transmissibility caused by higher affinity to ACE2 receptors and immune evasion are deduced from amino acid variations analyzed in the study., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Al Qurashi et al.)

Mercury (Hg) is a widely distributed and bioavailable metal of public health concern, with many known human toxicities, but data regarding mercury's influence on thyroid cancer (TC) is scarce. Mercury is known to impact several molecular pathways implicated in carcinogenesis, and its proclivity for bioaccumulation in the thyroid suggests a potential modulatory effect. We conducted a literature/systematic review of studies between 1995-2022 intending to define better and establish relationships between these two entities, congregate the evidence for mercury's potential role in thyroid carcinogenesis, and identify populations of interest for further study. Insufficient evidence precludes definitive conclusions on dietary mercury as a TC risk factor; however, several common mechanisms affected by mercury are crucial for TC development, including biochemical, endocrine, and reactive oxygen species effects. Quantitative analysis revealed associations between TC risk and mercury exposure. In three mercury studies, average urine levels were higher in TC patients, with a mean difference of 1.86 µg/g creatinine (95% CI = 0.32-3.41). In two studies investigating exposure to elevated mercury levels, the exposed group exhibited a higher risk of developing TC, with a relative risk of 1.90 (95% CI = 1.76-2.06). In three thyroid tissue studies, mercury levels (ppm) were higher in TC patients, averaging 0.14 (0.06-0.22) in cancerous cases (N = 178) and 0.08 (0.04-0.11) in normal thyroids (N = 257). Our findings suggest an association between mercury exposure and TC risk, implying a possible predisposing factor. Further research is necessary to reveal the clinical relevance of dietary and environmental mercury exposures in TC pathogenesis., (© 2024. The Author(s).)

The genotyping of long non-coding RNA (lncRNA)-related single-nucleotide polymorphisms (SNPs) could be associated with cancer risk and/or progression. This study aimed to analyze the angiogenesis-related lncRNAs MALAT1 (rs3200401) and MIAT (rs1061540) variants in patients with ovarian cancer (OC) using "Real-Time allelic discrimination polymerase chain reaction" in 182 formalin-fixed paraffin-embedded (FFPE) samples of benign, borderline, and primary malignant ovarian tissues. Differences in the genotype frequencies between low-grade ovarian epithelial tumors (benign/borderline) and malignant tumors and between high-grade malignant epithelial tumors and malignant epithelial tumors other than high-grade serous carcinomas were compared. Odds ratios (ORs)/95% confidence intervals were calculated as measures of the association strength. Additionally, associations of the genotypes with the available pathological data were analyzed. The heterozygosity of MALAT1 rs3200401 was the most common genotype (47.8%), followed by C/C (36.3%). Comparing the study groups, no significant differences were observed regarding this variant. In contrast, the malignant epithelial tumors had a higher frequency of the MIAT rs1061540 C/C genotype compared to the low-grade epithelial tumor cohorts (56.7% vs. 37.6, p = 0.031). The same genotype was significantly higher in high-grade serous carcinoma than its counterparts (69.4% vs. 43.8%, p = 0.038). Multivariate Cox regression analysis showed that the age at diagnosis was significantly associated with the risk of OC development. In contrast, the MIAT T/T genotype was associated with a low risk of malignant epithelial tumors under the homozygote comparison model (OR = 0.37 (0.16-0.83), p = 0.017). Also, MIAT T allele carriers were less likely to develop high-grade serous carcinoma under heterozygote (CT vs. CC; OR = 0.33 (0.12-0.88), p = 0.027) and homozygote (TT vs. CC; OR = 0.26 (0.07-0.90), p = 0.034) comparison models. In conclusion, our data provide novel evidence for a potential association between the lncRNA MIAT rs1061540 and the malignant condition of ovarian cancer, suggesting the involvement of such lncRNAs in OC development.

Background: Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood., Methods: A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to March 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of bias. The Cochrane Collaboration's tool was used for assessing risk of bias. We identified human, in vivo , and in vitro research studies utilizing RFA for tumor tissues. We required that the studies included at least one of the following: complications, recurrence, or survival, and took interest to studies identifying cellular signaling pathway patterns after RFA. Descriptive statistical analysis was performed in 'R' software including mean and confidence interval., Results: The most frequent cancers studied were liver and lung cancers accounting for 57.4% (N=995) and 15.4% (N=267), followed by esophageal (N=190) and breast cancer (N=134). The most common reported complications were bleeding (19%) and post-operative pain (14%). In our literature search, four independent studies showed upregulation and activation of the VEGF pathway following RFA, four showed upregulation and activation of the AKT pathway following RFA, three studies demonstrated involvement of matrix metalloproteinases, and four showed upregulation of c-Met protein following RFA., Conclusions: In our review and meta-analysis, we identify several proteins and pathways of interest of which are important in wound healing, angiogenesis, and cellular growth and survival. These proteins and pathways of interest may implicate areas of research towards RFA resistance and cancer recurrence., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-555/coif). The series “RFA and Recent Innovations in Endocrine Surgery” was commissioned by the editorial office without any funding or sponsorship. E.K. served as the unpaid Guest Editor of the series and serves as an Editor-in-Chief of Gland Surgery from May 2017 to April 2024. E.T. receives a research grant (THYROIDGRANT2021-0000000232) from the Bite Me Cancer and facilitated by the American Thyroid Association. The authors have no other conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Introduction Obesity is a complex health issue affecting millions worldwide, characterized by excessive body fat accumulation, often leading to various health complications. Bariatric surgeries are effective interventions for severe obesity, assisting patients in attaining substantial weight reduction and enhancing their overall well-being. This study aimed to assess obesity patterns and bariatric surgery prevalence in the Northern Borders region of Saudi Arabia to increase community knowledge and awareness about obesity and bariatric surgery. Methods This cross-sectional study included 386 residents in the Northern Borders region, Saudi Arabia. The participants completed a previously validated self-administered electronic questionnaire, and the confidentiality of the collected data was ensured. Results Nearly 58.3% of the participants (31-40 years), with a predominance of females, had a body mass index (BMI) >30, and 33.7% had undergone bariatric surgery. Most participants (92.5%) were aware that obesity is associated with significant medical issues, 98.2% appreciated that there is a surgical method to reduce weight, and 58.8% indicated that the procedure was not safe. Additionally, the majority of the respondents (57.0%) were not sure about the complications of weight-loss surgeries, and only 28.0% knew that surgeries for obesity and their complications may lead to death. Significant associations were found between age, education level, and BMI concerning the knowledge of obesity/bariatric surgery (p=0.003, 0.001, 0.002), respectively. However, gender and work status did not show such associations (p> 0.05). Conclusion Our study highlighted a lack of knowledge among the community regarding the safety, potential complications, and survival outcomes associated with obesity and bariatric surgery that could be due to ignorance and reluctance to pursue bariatric surgery to overcome morbid obesity. Significantly, the study found a relationship between age, education level, BMI, and knowledge of obesity and bariatric surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alanazi et al.)

Background: Epistaxis is a relatively common condition, particularly among children, necessitating that parents be well informed about its effective management., Objectives: This study aims to explore the current level of awareness among parents in the Arar region, Saudi Arabia, regarding the first aid management of epistaxis and to highlight the importance of education in empowering parents to handle such situations., Methods: A cross-sectional study was conducted using a survey distributed among the Arar population (aged >18 years) who had at least one child and were willing to participate. Data were collected between mid-July and the end of September 2023 using a self-administered questionnaire, which included a consent form, sociodemographic and background items, and epistaxis knowledge-related questions., Results: A total of 342 participants (27.8% males) completed the questionnaire. It was observed that 47.4% of the participants' children had experienced epistaxis. Only around half of them (n=84; 51.9%) had received first aid management for epistaxis, and only 40.4% of the parents correctly identified all the necessary steps for managing it through first aid. There was inadequate knowledge regarding the causes/risk factors and appropriate first aid techniques for epistaxis. Certain sociodemographic factors were significantly associated with better knowledge of first aid management of epistaxis, such as female gender (p = 0.003), older participants (p = 0.002), and a higher educational level (p = 0.001)., Conclusion: The study found low awareness of first aid management of epistaxis among parents residing in Arar, Saudi Arabia. Factors related to the demographic characteristics of the study participants were associated with this level of knowledge. These findings emphasize the need to improve awareness about first aid management of epistaxis, particularly among younger individuals, males, and those with limited education. Effective interventions should be developed to enhance first aid training, considering the specific risk factors associated with epistaxis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Elsayed Elboraei et al.)

Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12-18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accurately diagnosed thyroid malignancy regardless of BRAF mutation or Hashimoto's thyroiditis status, overcoming genetic and autoimmune heterogeneity. A high preoperative circulating ratio predicted aggressive disease features, including lymph node metastasis, extrathyroidal extension, progression/relapse, and recurrence. Although the preoperative plasma ratio was elevated in patients with unfavorable outcomes, it had limited utility for post-surgical monitoring. In conclusion, the MMP9/miR-145 ratio is a promising biomarker in PTC that bridges genetic and immunological variabilities, enhancing preoperative diagnosis and prognostication across diverse patient subgroups. It accurately stratifies heterogenous cases by aggressiveness. The longitudinal trends indicate decreasing applicability for post-thyroidectomy surveillance. Further large-scale validation and protocol standardization can facilitate clinical translation of the MMP9/miR-145 ratio to guide personalized thyroid cancer management.

Diabetes is a complex condition, and the causes are still not fully understood. However, a growing body of evidence suggests that exposure to air pollution could be linked to an increased risk of diabetes. Specifically, exposure to certain pollutants, such as particulate Matter and Ozone, has been associated with higher rates of diabetes. At the same time, air pollution has also been linked to an increased risk of thyroid cancer. While there is less evidence linking air pollution to thyroid cancer than to diabetes, it is clear that air pollution could have severe implications for thyroid health. Air pollution could increase the risk of diabetes and thyroid cancer through several mechanisms. For example, air pollution could increase inflammation in the body, which is linked to an increased risk of diabetes and thyroid cancer. Air pollution could also increase oxidative stress, which is linked to an increased risk of diabetes and thyroid cancer. Additionally, air pollution could increase the risk of diabetes and thyroid cancer by affecting the endocrine system. This review explores the link between diabetes and air pollution on thyroid cancer. We will discuss the evidence for an association between air pollution exposure and diabetes and thyroid cancer, as well as the potential implications of air pollution for thyroid health. Given the connections between diabetes, air pollution, and thyroid cancer, it is essential to take preventive measures to reduce the risk of developing the condition., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Estimation of the prevalence of chronic conditions is pivotal to effective healthcare planning and management. Therefore, our objective was to systemically review previous literature about the prevalence of chronic diseases among residents of Northern Borders Province (NBP) in Saudi Arabia. The electronic search has been done using scientific databases (PubMed, Ebsco, SciFinder, and Web of Science) and search engines up to September 2021. The following main key terms: chronic disease OR chronic conditions AND prevalence AND Northern Borders Province OR Northern Borders AND Saudi Arabia were applied. Other related terms with a more specific search were done with names of the main cities in the province and the most common diseases in Saudi Arabia. Duplicates were removed electronically by Endnote and manually. Extracted data were tabulated in the literature matrix. The risk of bias and quality of included studies were assessed using the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) checklist. Out of 63 observational studies that were assessed for eligibility, 21 observational studies were included to synthesize the evidence. These studies were conducted on Arar (n=16), Turaif (n=2), and Rafha (n=1), while the remaining were national studies in which NBP was one of the included regions (n=2). The most frequently studied diseases were diabetes (4 records), psychological diseases (4 records), and obesity (3 records). The most prevalent disease was gastroesophageal reflux disease (GERD), with an estimated prevalence of 61% among adults in Arar city. In conclusion, although some research is conducted about chronic diseases somewhere in NBP, further studies are needed to study chronic diseases using a representative sample of the whole NBP population., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2023 Alenzi et al.)

Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21-90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient's cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype ( p = 0.005) and any melanoma with a high mitotic rate ( p = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma.

Long non-coding RNAs (lncRNAs) have key roles in tumor development and the progress of many cancers, including breast cancer (BC). This study aimed to explore for the first time the association of the migration/differentiation-associated lncRNA SENCR rs12420823C/T variant with BC risk and prognosis. Genotyping was carried out for 203 participants (110 patients and 93 controls) using the TaqMan allelic discrimination technique. The corresponding clinicopathological data, including the recurrence/survival times, were analyzed with the different genotypes. After adjustment by age and risk factors, the T/T genotype carrier patients were more likely to develop BC under homozygote comparison (T/T vs. C/C: OR = 8.33, 95% CI = 2.44-25.0, p = 0.001), dominant (T/T-C/T vs. C/C: OR = 3.70, 95% CI = 1.72-8.33, p = 0.027), and recessive (T/T vs. C/T-C/C: OR = 2.17, 95% CI = 1.08-4.55, p < 0.001) models. Multivariate logistic regression analysis showed that the T/T genotype carriers were more likely to be triple-negative sub-type (OR = 2.66, 95% CI = 1.02-6.95, p = 0.046), at a higher risk of recurrence (OR = 3.57, 95% CI = 1.33-9.59, p = 0.012), and had short survival times (OR = 3.9, 95% CI = 1.52-10.05, p = 0.005). Moreover, Cox regression analysis supported their twofold increased risk of recurrence (HR = 2.14, 95% CI = 1.27-3.59, p = 0.004). Furthermore, the predictive nomogram confirmed the high weight for SENCR rs12420823*T/T and C/T genotypes in predicting recurrence within the first year. The Kaplan-Meier survival curve demonstrated low disease-free survival (T/T: 12.5 ± 1.16 months and C/T: 15.9 ± 0.86 months versus C/C: 22.3 ± 0.61 months, p < 0.001). In conclusion, the LncRNA SENCR rs12420823*C/T may be associated with an increased risk of BC in women and could be a promising genetic variant for predicting recurrence and survival.

The Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) pandemic has transformed our appreciation of healthcare awareness worldwide. The amount of related data accumulated during this time has surpassed any other outbreak of a viral pathogen. Healthcare awareness is related to one of the nine pillars of the "World health organization (WHO) operational planning guidelines to support country preparedness and response". This review is structured around the awareness/knowledge, attitudes, and practices (KAP)-related publications in Saudi Arabia up to date to understand the impact of COVID-19 on these domains. The excellent communication effort response from governments, international, and individuals to keep the public informed about the outbreak is highlighted. Unraveling such impacts on the Saudi communities, including healthcare workers (HCWs)/professionals (HCPs), students, patients with different diseases, and non-professional individuals, is essential in containing the outbreak and planning preventive measures in case of future outbreaks., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Fawzy and AlSadrah.)

Objective: As trampoline use grows more popular in the United States, the frequency of injuries continues to climb. We hypothesized that toddlers would be at the highest risk for trampoline injuries requiring hospitalization., Methods: The National Electronic Injury Surveillance System database was examined for trampoline injuries from 2009 to 2018. Patients were categorized into 3 main age groups: toddlers (<2 years), children (2-12 years), and adolescents (13-18 years). Regression models were used to identify patients at high risk for injury or hospitalization., Results: There was a total of 800,969 meeting inclusion criteria, with 433,827 (54.2%) occurring at their own homes and 86,372 (18.1%) at the sporting venue. Of the total, 36,789 (4.6%) were admitted to a hospital. Fractures (N = 270,884, 34%), strain/sprain injuries (N = 264,990, 33%), followed by skin contusions/abrasions (N = 115,708, 14%) were the most common diagnoses. The most frequent injury sites were lower and upper extremities accounting for 329,219 (41.1%) and 244,032 (30.5%), whereas 175,645 (21.9%) had head and neck injuries. Musculoskeletal injuries (74%) and concussions (2.6%) were more frequent in adolescents than children (67.6% and 1.6%) and toddlers (56.3% and 1.3%). Internal organ and soft tissue injuries were frequent in toddlers. There were no fatalities reported in the injured patients. Multivariate analysis showed adolescents, female sex, extremity injuries, and musculoskeletal injuries were associated with hospitalization. Injury at a sporting venue was not associated with hospitalization., Conclusions: Adolescents and girls are at increased risk of trampoline injury, warranting hospitalization. Safety standards may help prevent extremity and musculoskeletal injuries in the pediatric population. Finally, use of trampolines at sporting venues does not appear to be particularly dangerous., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The angiotensin-converting enzyme-2 ( ACE2 ) is recognized to be the fundamental receptor of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), responsible for the worldwide Coronavirus Disease-2019 (COVID-19) epidemic. However, genetic differences between people besides racial considerations and their relation to disease susceptibility are still not fully elucidated., Main Body: To uncover the role of ACE2 in COVID-19 infection, we reviewed the published studies that explore the association of COVID-19 with the functional characteristics of ACE2 and its genetic variations. Notably, emerging studies tried to determine whether the ACE2 variants and/or expression could be associated with SARS-CoV/SARS-CoV2 have conflicting results. Some researchers investigated the potential of "population-specific" ACE2 genetic variations to impact the SARS-CoV2 vulnerability and suggested no ethnicity enrichment for ACE2 polymorphisms that could influence SARS-CoV2 S-protein binding. At the same time, some studies use data mining to predict several ACE2 variants that could enhance or decline susceptibility to SARS-CoV. On the other hand, fewer studies revealed an association of ACE2 expression with COVID-19 outcome reporting higher expression levels of ACE2 in East Asians., Conclusions: ACE2 gene variants and expression may modify the deleterious consequences of SARS-CoV2 to the host cells. It is worth noting that apart from the differences in gene expression and the genetic variations of ACE2 , many other environmental and/or genetic factors could modify the disease outcome, including the genes for the innate and the adaptive immune response., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Background: The expression signature of deregulated long non-coding RNAs (lncRNAs) and related genetic variants is implicated in every stage of tumorigenesis, progression, and recurrence. This study aimed to explore the association of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene expression and the rs2383207A>G intronic variant with breast cancer (BC) risk and prognosis and to verify the molecular role and networks of this lncRNA in BC by bioinformatics gene analysis., Methods: Serum CDKN2B-AS1 relative expression and rs2383207 genotypes were determined in 214 unrelated women (104 primary BC and 110 controls) using real-time PCR. Sixteen BC studies from The Cancer Genome Atlas (TCGA) including 8925 patients were also retrieved for validation of results., Results: CDKN2B-AS1 serum levels were upregulated in the BC patients relative to controls. A/A genotype carriers were three times more likely to develop BC under homozygous (OR = 3.27, 95% CI 1.20-8.88, P = 0.044) and recessive (OR = 3.17, 95% CI 1.20-8.34, P = 0.013) models. G/G homozygous patients had a higher expression level [median and quartile values were 3.14 (1.52-4.25)] than A/G [1.42 (0.93-2.35)] and A/A [1.62 (1.33-2.51)] cohorts (P = 0.006). The Kaplan-Meier curve also revealed a higher mean survival duration of G/G cohorts (20.6 months) compared to their counterparts (A/A: 15.8 and A/G: 17.2 months) (P < 0.001). Consistently, BC data sets revealed better survival in cohorts with high expression levels (P = 0.003). Principal component analysis (PCA) showed a deviation of patients who had shorter survival towards A/A and A/G genotypes, multiple lesions, advanced stage, lymphovascular invasion, and HER2 + receptor staining. Ingenuity Pathway Analysis (IPA) showed key genes highly enriched in BC with CDKN2B-AS1., Conclusions: The findings support the putative role of CDKN2B-AS1 as an epigenetic marker in BC and open a new avenue for its potential use as a therapeutic molecular target in this type of cancer.

Background: We aimed to systematically review the clinical and laboratory features of patients with the multisystem inflammatory syndrome in pediatrics diagnosed during the COVID-19 pandemic., Data Sources: A literature search in Web of Science, PubMed, Scopus, and Science Direct was made up to June 29, 2020., Results: Analysis of 15 articles (318 COVID-19 patients) revealed that although many patients presented with the typical multisystem inflammatory syndrome in pediatrics, Kawasaki-like features as fever (82.4%), polymorphous maculopapular exanthema (63.7%), oral mucosal changes (58.1%), conjunctival injections (56.0%), edematous extremities (40.7%), and cervical lymphadenopathy (28.5%), atypical gastrointestinal (79.4%) and neurocognitive symptoms (31.8%) were also common. They had elevated serum lactic acid dehydrogenase, D-dimer, C-reactive protein, procalcitonin, interleukin-6, troponin I levels, and lymphopenia. Nearly 77.0% developed hypotension, and 68.1% went into shock, while 41.1% had acute kidney injury. Intensive care was needed in 73.7% of cases; 13.2% were intubated, and 37.9% required mechanical ventilation. Intravenous immunoglobulins and steroids were given in 87.7% and 56.9% of the patients, respectively, and anticoagulants were utilized in 67.0%. Pediatric patients were discharged after a hospital stay of 6.77 days on average (95% CI 4.93-8.6)., Conclusions: Recognizing the typical and atypical presentation of the multisystem inflammatory syndrome in pediatric COVID-19 patients has important implications in identifying children at risk. Monitoring cardiac and renal decompensation and early interventions in patients with multisystem inflammatory syndrome is critical to prevent further morbidity.