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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. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of radioactive iodine (RAI) ablation is a common therapy among adults with differentiated thyroid cancer. However, the clinical outcomes and long-term effects of this treatment in pediatric thyroid cancer patients remain uncertain. The aim of our retrospective cohort study was to assess the risks and survival benefits of RAI in pediatric thyroid cancer patients. Using data from patients aged 21 years or younger with differentiated thyroid cancer from the SEER cancer registries, we confirmed RAI did not show any significant impact on recurrence, second malignancy, or mortality. There was no significant difference in long-term survival between pediatric patients who received RAI and those who did not. Thus, excellent clinical outcomes are achieved regardless of RAI use in differentiated pediatric thyroid cancer. 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. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder that affects individuals across all age groups, including children, adolescents, and adults. The ADHD etiology encompasses a lack of several nutrients and food compositions. Some applied strategies, such as increased intake of specific nutrients, were proposed as additional therapy for this condition. In our narrative review, we explored the relationship between dietary patterns and ADHD by searching through "Google Scholar, Scopus, and PubMed" for relevant studies. This review sheds light on the connection between dietary patterns and ADHD and provides a concise summary about practicing these dietary therapies. Several studies reported that unhealthy eating habits were positively correlated with ADHD, while healthy eating habits showed a negative correlation. Furthermore, there is a potential association between ADHD and deficiency in certain nutrients, including magnesium, iron, zinc, polyunsaturated fatty acids, and vitamin D. However, despite the promising nature of the dietary modifications as strategies for managing ADHD, the need for more robust scientific evidence to validate their effectiveness is highly recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Skin cancer accounts for 2.2% of newly diagnosed cancer cases in Saudi Arabia, according to the Saudi Cancer Registry 2020. While studies indicate skin cancers primarily occur in the extremities, head, neck and mucosal regions, comprehensive data on prevalence, mortality, morbidity, treatment modalities and overall burden in Saudi Arabia are lacking. This scoping review aimed to analyze existing literature on skin cancer within the Saudi population, assess its prevalence and potential risk factors and identify knowledge gaps. We systematically searched PubMed, Web of Science, SCOPUS and Science Direct databases, utilizing the Rayyan QCRI tool for data organization and synthesis. The review included 15 studies encompassing 2,596 patients, of whom 1,378 (56.2%) were male. Our analysis revealed basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma as the most common types. BCC and SCC predominantly affected the head and neck, while melanoma more often impacted the extremities. Surgical intervention was the primary treatment approach. Key risk factors identified included occupational pesticide exposure, UV radiation susceptibility and genetic predisposition. This review highlights the need for a comprehensive nationwide screening program to evaluate the prevalence of skin-related issues in Saudi Arabia and address the identified knowledge gaps in skin cancer epidemiology and management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]