COVID-19 mRNA Vaccination Responses in Individuals With Sickle Cell Disease: ASH RC Sickle Cell Research Network Study.

Children and adults with sickle cell disease (SCD) have increases in morbidity and mortality with COVID-19 infections. The ASH Research Collaborative Sickle Cell Disease Research Network performed a prospective COVID-19 vaccine study to assess antibody responses and analyze whether mRNA vaccination precipitated any adverse effects unique to individuals with SCD. Forty-one participants received two doses of the Pfizer-BioNTech vaccine and provided baseline blood samples prior to vaccination and 2 months after the initial vaccination for analysis of IgG reactivity against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Six month IgG reactivity against the viral RBD was also available in 37 patients. Post-vaccination reactogenicity was common and similar to the general population. There were no fevers that required inpatient admission. Vaso-occlusive pain within 2-3 days of 1st or 2nd vaccination was reported by 5 (12%) participants including 4 (10%) who sought medical care. Twenty-seven participants (66%) were seropositive at baseline, and all 14 (34%) initially seronegative participants converted to seropositive post vaccination. Overall, mRNA vaccination had a good risk benefit-profile in individuals with sickle cell disease.This mRNA vaccine study also marks the first evaluation of vaccine safety and antibody response in very young children with sickle cell disease. NCT05139992.

Medial swivel dislocation with impacted navicular bone into the talar head: A case report.

Medial swivel dislocation is a rare subtype of midtarsal bone dislocation, mostly associated with fracture rather than isolated dislocation. It is caused by medially or laterally direct forces to the midfoot. In case of failed closed reduction of the deformity, the patient should undergo open reduction and stabilization of the injury as soon as possible. We are presenting a 17-year-old, male, who sustained a left ankle injury and presented with a deformity, closed reduction of the deformity failed multiple times, and the patient was taken for open reduction and stabilization of the deformity in the operating theater. Intra-operatively, the dislocation was locked with the lateral process of the navicular being impacted into the taller head. Six months following the injury the patient was back to his pre-injury status and did not have any recurrent dislocation of the midfoot.

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study.

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund's complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

The relationship between Coronavirus Disease-19 (COVID-19) and ischemic priapism: a case-control study.

This multicentre retrospective study was conducted in 3 university hospitals in Egypt between April 2020 and June 2022. The aim was to assess the relation between Coronavirus Disease-19 (COVID-19) and ischemic priapism. Forty-three ischemic priapism patients were diagnosed and divided into two groups (30 in group I with ischemic priapism only, and 13 in group II with both ischemic priapism and COVID-19). Further sub-classification of COVID-19 patients according to the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection severity was done. Cavernosal aspiration was successful in 25 patients (83.3%) in group I and 12 (92.3%) in group II. Long term follow-up proved moderate to severe erectile dysfunction in 6 patients (20.0%) and 1 (7.7%) in group I and II, respectively. All those with severe erectile dysfunction were managed by distal shunt and prepared for penile prosthesis placement. The median duration of ischemic priapism was significantly longer in patients with severe erectile dysfunction [19 vs. 7 h, P = 0.01]. There was no statistically significant difference between both groups regarding patients' age (p = 0.8), required priapism management (p = 0.4), priapism recurrence (p = 0.1), and erectile dysfunction severity (p = 0.5). Ischemic priapism in COVID-19 patients can occur not only in severe, but also in mild or even asymptomatic cases. COVID-19 did not influence the ischemic priapism treatment protocol and post-treatment erectile function. COVID-19 and ischemic priapism seem to have a coincidence relation rather than a causal.

Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients.

OBJECTIVE: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID. MATERIALS AND METHODS: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies. RESULTS: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91). DISCUSSION: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.

Effect of autologous platelet-rich plasma on the fertility and quality of cryopreserved buffalo bull semen: a comparative study using OptiXcell® and tris egg yolk extenders.

BACKGROUND: Buffalo spermatozoa have a distinct membrane structure that makes them more vulnerable to cryopreservation, resulting in lower-quality post-thawed sperm. This decreases the success rate of artificial insemination in buffaloes. Understanding and addressing these specific vulnerabilities are essential for improving reproductive techniques in buffalo populations. The properties of cryopreserved buffalo bull semen were examined in this study regarding the impact of adding autologous platelet-rich plasma (PRP) to OptiXcell® or Tris egg yolk-based extenders. Ten buffalo bulls were used to collect semen. Each bull's ejaculate was separated into two main equal amounts, each of which was then diluted with either OptiXcell® or Tris egg yolk-based extender, supplemented with various PRP concentrations (5%, 10%, and 15%), and the control (0%), before being cryopreserved according to established protocols. Following equilibration and thawing, the quality and functionality of the sperm were evaluated, along with the antioxidant enzyme activities (GSH and TAC), malondialdehyde (MDA) content, and in vivo fertilization rate of the thawed semen. RESULTS: All PRP concentrations in both extenders, particularly 10% PRP, improved the quality and functionality of the sperm in both equilibrated and frozen-thawed semen. Additionally, the antioxidant enzyme activities in both extenders were higher in the PRP-supplemented groups compared to the control group in thawed semen (P < 0.05). All post-thaw sperm quality, antioxidant enzyme activities, and functionality aside from DNA integrity were higher (P < 0.05) in the PRP-supplemented OptiXcell® than in the PRP-supplemented Tris egg yolk-based extender. The fertility of cryopreserved semen in the extenders supplemented with 10% and 15% PRP increased (P < 0.05) significantly more than that of the control extenders, with 10% PRP being the optimum concentration in OptiXcell® (80%) compared to that of Tris egg yolk-based extender (66.67%) and control of two extenders (53.33% and 46.67%, respectively). CONCLUSIONS: Even though autologous PRP-supplemented extenders have a protective impact on equilibrated and cryopreserved semen, 10% PRP-supplemented OptiXcell® extenders are more effective at preserving post-thaw semen quality, functionality, and antioxidant capacity, which increases the in vivo fertility of buffalo bulls.

Human Y chromosome haplogroup L1-M22 traces Neolithic expansion in West Asia and supports the Elamite and Dravidian connection.

West and South Asian populations profoundly influenced Eurasian genetic and cultural diversity. We investigate the genetic history of the Y chromosome haplogroup L1-M22, which, while prevalent in these regions, lacks in-depth study. Robust Bayesian analyses of 165 high-coverage Y chromosomes favor a West Asian origin for L1-M22 ∼20.6 thousand years ago (kya). Moreover, this haplogroup parallels the genome-wide genetic ancestry of hunter-gatherers from the Iranian Plateau and the Caucasus. We characterized two L1-M22 harboring population groups during the Early Holocene. One expanded with the West Asian Neolithic transition. The other moved to South Asia ∼8-6 kya but showed no expansion. This group likely participated in the spread of Dravidian languages. These South Asian L1-M22 lineages expanded ∼4-3 kya, coinciding with the Steppe ancestry introduction. Our findings advance the current understanding of Eurasian historical dynamics, emphasizing L1-M22's West Asian origin, associated population movements, and possible linguistic impacts.

Unveiling the multifaceted antiproliferative efficacy of Cichorium endivia root extract by dual modulation of apoptotic and inflammatory genes, inducing cell cycle arrest, and targeting COX-2.

Chicory (Cichorium endivia L. divaricatum) is a renowned medicinal plant traditionally used for various ailments, yet the pharmacological potential of its roots, particularly in terms of antitumor activity, remains elusive. In the present study, we explore, for the first time, the metabolomic profile of ethanolic extract from Cichorium endivia roots (CIR) and further unveil its antiproliferative potential. The untargeted phytochemical analysis UPLC/T-TOF-MS/MS identified 131 metabolites in the CIR extract, covering acids, amino acids, flavonoids, alkaloids, nucleotides, and carbohydrates. The antiproliferative activity of the CIR extract was tested in 14 cancer cell lines, revealing significant cytotoxicity (IC50: 2.85-29.15 µg mL-1) and a high selectivity index. Among the cells examined, the CIR extract recorded the most potent antiproliferative activity and selectivity toward HepG2 and Panc-1 cells, with an IC50 of 2.85 µg mL-1 and 3.86 µg mL-1, respectively, and SI > 10. Insights into the mode of action of the antiproliferative activity revealed that CIR extract induces cell arrest in the S phase while diminishing cell distribution in the G0/G1 and G2/M phases in HepG-2 and Panc-1 cells. Flow cytometric and RT-PCR analysis revealed that the CIR extract significantly triggers apoptosis and modulates the expression of pro-apoptotic and anti-apoptotic genes. Furthermore, the CIR extract exhibited a pronounced anti-inflammatory activity, as evidenced by down-regulating key cytokines in LPS-induced RAW 264.7 cells and selectively inhibiting the COX-2 enzyme. Finally, the CIR extract showed a robust total antioxidant capacity, together with potent free radicals and metal scavenging properties, highlighting its role in alleviating oxidative stress. Taken together, this study highlights the multifaceted therapeutic potential of CIR extract as a natural-based antitumor supplement.

Simplified biplanar (0-90°) versus monoplanar renal puncture technique in flank free modified supine percutaneous nephrolithotomy regarding outcomes and learning curve: Randomized clinical trial.

Objective: To evaluate the learning curve and the success rate of the biplanar (0-90°) puncture technique in the flank-free modified supine position in comparison to the monoplanar puncture technique. Methods: Randomized controlled study included 68 patients more than 18 years with renal stones more than 2 cm from August 2021 to August 2022 were randomly classified by closed envelope method into group A (34 patients) scheduled for monoplanar renal puncture technique in flank-free modified supine PCN. Meanwhile, group B (34 patients) was scheduled for the 0-90° simplified fluoroscopic puncture technique. Morbid obese patients and patients with contraindications for PNL were omitted from the study. Results: There was no significant difference between both groups regarding stone distribution and patients' demographic data. There was a significant difference between both groups regarding puncture attempts. In 88.2% of patients in group B (Biplanar group), the success of renal puncture occurred from the 1st puncture attempt while in 11.2% of patients in group A (monoplanar group). There was a statistically significant difference between both groups in fluoroscopy time and total operation time (p-value <0.001 & p-value: 0.001), respectively. The stone-free rate was 85.2% vs. 88.2% in both groups, respectively, without significant difference. In this study puncture, attempt trials and puncture time were used as indicators for the easiness and rapid educability of the biplanar (0-90°) fluoroscopic guided renal puncture technique. In the biplanar (0-90°) group after 24 cases, the learning curve had reached the plateau. Conclusion: Biplanar (0-90°) puncture technique in flank-free modified supine position allows an easy puncture technique with an easy learning curve without affecting the success rate or complication rate.

New Thieno[2,3-d]pyrimidines as Anticancer VEGFR-2 Inhibitors with Apoptosis Induction: Design, Synthesis, and Biological and In Silico Studies.

BACKGROUND: Vascular endothelial growth factor receptor-2 (VEGFR-2) is a critical protein involved in tumor progression, making it an attractive target for cancer therapy. OBJECTIVE: This study aimed to synthesize and evaluate novel thieno[2,3-d]pyrimidine analogues as potential anticancer VEGFR-2 inhibitors. METHODS: The thieno[2,3-d]pyrimidine analogues were synthesized following the pharmacophoric features of VEGFR-2 inhibitors. The anticancer potential was assessed against PC3 and HepG2 cell lines. The VEGFR-2 inhibition was evaluated through IC50 determination. Cell cycle analysis and apoptosis assays were performed to elucidate the mechanisms of action. Molecular docking, molecular dynamics simulations, MM-GBSA, and PLIP studies were conducted to investigate the binding affinities and interactions with VEGFR-2. Additionally, in silico ADMET studies were performed. RESULTS: Compound 8b demonstrated significant anti-proliferative activities with IC50 values of 16.35 µM and 8.24 µM against PC3 and HepG2 cell lines, respectively, surpassing sorafenib and exhibiting enhanced selectivity indices. Furthermore, compound 8b showed an IC50 value of 73 nM for VEGFR-2 inhibition. Cell cycle analysis revealed G2-M phase arrest, while apoptosis assays demonstrated increased apoptosis in HepG2 cells. Molecular docking and dynamic simulations confirmed the binding affinity and interaction of compound 8b with VEGFR-2, supported by MMGBSA and PLIP studies. In silico ADMET studies indicated the drug development potential of the synthesized thieno[2,3-d]pyrimidines. CONCLUSION: The study highlights compound 8b as a promising VEGFR-2 inhibitor with potent anti-proliferative activities. Its mechanism of action involves cell cycle arrest and induction of apoptosis. Further, molecular docking and dynamic simulations support the strong binding affinity of compound 8b to VEGFR-2.

Exploring the linkages between social media use, self-esteem, and academic performance among nursing students in Saudi Arabia: A descriptive correlational study.

Background: The prevalence of social media influence in education makes it necessary to investigate how it might affect nursing students' academic achievement and sense of self. To our knowledge, the associations between academic performance, self-esteem, and social media usage among nursing students from Saudi Arabia remain understudied. Objective: This study aimed to examine the relationships between academic performance, self-esteem, and the utilization of social media platforms by Saudi Arabian nursing students. Methods: This descriptive correlational study employed a convenience sample of 220 nursing students (response rate 95.2%). An online survey with questions about demographics, students' academic performance, social media usage, and self-esteem was used for data collection from 1 March to May 2023. Pearson correlation coefficients, independent t-tests, Analysis of Variance, and hierarchical regression were used for data analysis. Results: Social media use had an average score of 3.60 ± 0.66, self-esteem was 2.13 ± 0.27, and academic performance was 3.95 ± 0.58. The students' academic performance related positively to the utilization of social media platforms (r = 0.210, p <0.01). There were statistically positive correlations between academic purpose and social motives domains of utilizing social media and academic performance (r = 0.304, p <0.01; r = 0.208, p <0.01) respectively. The amount of time students spent on social media was not related to their self-esteem (r = 0.047, p >0.05). The students' self-esteem was unrelated to their academic achievement (r = 0.059, p >0.05). Conclusions: Utilizing social media channels can assist nursing students in improving their academic achievement. Therefore, nursing educators and decision-makers in nursing education have the opportunity to establish collaborative learning environments by integrating social media. This approach aims to improve communication, enhance the learning experience, and ultimately improve the academic achievements of nursing students.

Harnessing molecular hybridization approach to discover novel quinoline EGFR-TK inhibitors for cancer treatment.

Aim: Using molecular hybridization approach, novel 18 quinoline derivatives (6a-11) were designed and synthesized as EGFR-TK inhibitors. Materials & methods: The antiproliferative activity was assessed against breast (MCF-7), leukemia (HL-60) and lung (A549) cancer cell lines. Moreover, the most active quinoline derivatives (6d and 8b) were further investigated for their potential as EGFR-TK inhibitors. In addition, cell cycle analysis and apoptosis induction activity were conducted. Results: A considerable cytotoxic activity was attained with IC50 values spanning from 0.06 to 1.12 µM. Besides, the quinoline derivatives 6d and 8b displayed potent inhibitory activity against EFGR with IC50 values of 0.18 and 0.08 µM, respectively. Conclusion: Accordingly, the afforded quinoline derivatives can be used as promising lead anticancer candidates for future optimization.

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Synthesis, surface activity, and corrosion inhibition capabilities of new non-ionic gemini surfactants.

Several environmentally acceptable non-ionic gemini surfactants are synthesized in this work using natural sources, including polyethenoxy di-dodecanoate (GSC12), polyethenoxy di-hexadecanoate (GSC16), and polyethenoxy di-octadecenoate (GSC18). The produced surfactants are confirmed by spectrum studies using FT-IR, 1HNMR, and 13CNMR. It explored and examined how the length of the hydrocarbon chain affected essential properties like foaming and emulsifying abilities. Surface tension examinations are used to assess the surface activity of the examined gemini surfactants. The lower value of critical micelle concentrations (0.381 × 10-4M) is detected for GSC18. Their spontaneous character is shown by the negative values of the free energy of adsorption (ΔGads) and micellization (ΔGmic) which arranged in the order GSC18 > GSC16 > GSC12. Based on theoretical, weight loss, and electrochemical investigations, these novel surfactants were investigated for their possible use in inhibiting carbon steel from corroding in 1 M HCl. Measuring results show that GSC18 inhibits corrosion in carbon steel by 95.4%. The isotherm of adsorption evaluated for the investigated inhibitors and their behavior obeys Langmuir isotherm.

Menopausal symptom management: Fezolinetant's varied doses provide effective relief for vasomotor symptoms in women - A meta-analysis of 3291 participants.

Menopause represents the physiological transition when a woman's reproductive period ends associated with a variety of symptoms, including vasomotor symptoms, such as night sweats and hot flashes. This systematic review and meta-analysis aimed to assess the effectiveness and safety of oral Fezolinetant for treating vasomotor symptoms associated with menopause. Five electronic databases were searched from their inception until May 2023. Via the Cochrane risk of bias tool, two reviewers assessed the studies' quality. The primary outcomes were a decrease in VMSs frequency and severity and safety outcomes at 4 and 12 weeks. Data were extracted and then analyzed using RevMan software. This meta-analysis included six trials with a total of 3291 women that compared Fezolinetant to a placebo in the treatment of menopausal VMSs. After 4 and 12 weeks of therapy, fezolinetant at 30 mg QD or 45 mg QD substantially decreased the frequency and severity of VMSs per 24 hours compared to placebo. Fezolinetant at 90 mg BID, 30 mg QD, or 45 mg QD did not show a significant difference in the rate of treatment-emergent adverse events (TEAEs), headache, and TEAEs leading to permanent discontinuation compared to placebo. Fezolinetant proves to be a successful and well-tolerated remedy for menopausal women suffering from VMSs. Notably, the 45 mg daily dosage over 12 weeks exhibited significant efficacy. Nonetheless, extensive future trials are necessary to ascertain its long-term safety, effectiveness, and relative potency compared to alternative VMS treatments like hormone therapy.

La ménopause représente la transition physiologique lorsque la période de reproduction d'une femme se termine, associée à divers symptômes, notamment des symptômes vasomoteurs, tels que des sueurs nocturnes et des bouffées de chaleur. Cette revue systématique et méta-analyse visaient à évaluer l'efficacité et l'innocuité du Fezolinetant oral pour traiter les symptômes vasomoteurs associés à la ménopause. Cinq bases de données électroniques ont été consultées depuis leur création jusqu'en mai 2023. Via l'outil Cochrane sur le risque de biais, deux examinateurs ont évalué la qualité des études. Les principaux critères de jugement étaient une diminution de la fréquence et de la gravité des SVM ainsi que des critères de sécurité à 4 et 12 semaines. Les données ont été extraites puis analysées à l'aide du logiciel RevMan. Cette méta-analyse comprenait six essais portant sur un total de 3 291 femmes comparant Fezolinetant à un placebo dans le traitement des SVM ménopausiques. Après 4 et 12 semaines de traitement, le fézolinetant à la dose de 30 mg une fois par jour ou de 45 mg une fois par jour a considérablement réduit la fréquence et la gravité des SMV toutes les 24 heures par rapport au placebo. Le fézolinetant à la dose de 90 mg deux fois par jour, de 30 mg une fois par jour ou de 45 mg une fois par jour n'a pas montré de différence significative dans le taux d'événements indésirables survenus pendant le traitement (TEAE), de maux de tête et de TEAE conduisant à un arrêt définitif par rapport au placebo. Le fézolinetant s'avère être un remède efficace et bien toléré pour les femmes ménopausées souffrant de VMS. Notamment, la dose quotidienne de 45 mg sur 12 semaines a montré une efficacité significative. Néanmoins, de futurs essais approfondis sont nécessaires pour vérifier son innocuité, son efficacité et sa puissance relative à long terme par rapport aux traitements alternatifs du VMS comme l'hormonothérapie.

Integrated care of diabetes during pregnancy: a Qatari nationwide cohort.

Background: Diabetes in pregnancy (DIP) is associated with adverse fetal and maternal outcomes. DIP is classified as either pre-existing or new-onset diabetes mellitus (DM), which is classified into gestational DM (GDM) and newly detected type 2 (N-T2D). All pregnant women in Qatar who are not known to have pre-existing DM are offered screening for DIP during the first antenatal care visit and after 24 weeks gestation. The study aims to report the DIP screening rates, the prevalence of DIP, and the impact of the universal screening program on adverse pregnancy outcomes. Methods: This retrospective study included all women who gave birth in Hamad Medical Corporation (HMC) hospitals between 2019 and 2022. New-onset DIP was defined using the WHO-2013 criteria. The primary outcomes were the screening rates and the prevalence of DIP in Qatar. The secondary outcomes were the difference in preterm delivery, C-section, macrosomia, large for gestational age (LGA), small for gestational age (SGA), and intra-uterine fetal death (IUFD) between women with or without GDM. Findings: We included 94,422 women who gave birth to 96,017 neonates (85.7%) out of 112,080 neonates born nationwide. The number of women with pre-existing diabetes was 2496 women. Of 91,926 eligible women, 77,372 (84.2%) were screened for DIP. The prevalence of GDM is 31.6% (95% CI: 31.3-32.0%); N-T2D is 2.2% (95% CI: 2.1-2.3%), and pre-existing Type 2 DM and Type 1 DM was 2.6% (95% CI: 0.8-3.0%) and 0.2% (0.19-0.25), respectively. Compared to the non-GDM group, women with GDM were older (30.8 ± 5.3 versus 29.7 ± 5.2 years, p < 0.001). After adjusting for age, women with GDM had lower risk of IUFD and SGA (0.63 [95% CI 0.50-0.80, p < 0.001], 0.88 [95% CI 0.84-0.92, p < 0.001] respectively) but higher risk of C-section and LFD (1.07 [95% CI 1.04-1.10, p < 0.001], 1.09 [95% CI 1.01-1.15, p = 0.01], respectively, compared to women with no-GDM. Interpretation: Of the women eligible for screening, 84.2% were screened by the DIP program in Qatar. The prevalence of DIP in Qatar is 36.9%. Integrated care is critical for the screening and management of diabetes during pregnancy. Fundings: The authors did not receive any funding for this project.

New Theobromine Apoptotic Analogue with Anticancer Potential Targeting the EGFR Protein: Computational and In Vitro Studies.

AIM: The aim of this study was to design and examine a novel epidermal growth factor receptor (EGFR) inhibitor with apoptotic properties by utilizing the essential structural characteristics of existing EGFR inhibitors as a foundation. METHOD: The study began with the natural alkaloid theobromine and developed a new semisynthetic derivative (T-1-PMPA). Computational ADMET assessments were conducted first to evaluate its anticipated safety and general drug-likeness. Deep density functional theory (DFT) computations were initially performed to validate the three-dimensional (3D) structure and reactivity of T-1-PMPA. Molecular docking against the EGFR proteins was conducted to investigate T-1-PMPA's binding affinity and inhibitory potential. Additional molecular dynamics (MD) simulations over 200 ns along with MM-GPSA, PLIP, and principal component analysis of trajectories (PCAT) experiments were employed to verify the binding and inhibitory properties of T-1-PMPA. Afterward, T-1-PMPA was semisynthesized to validate the proposed design and in silico findings through several in vitro examinations. RESULTS: DFT studies indicated T-1-PMPA's reactivity using electrostatic potential, global reactive indices, and total density of states. Molecular docking, MD simulations, MM-GPSA, PLIP, and ED suggested the binding and inhibitory properties of T-1-PMPA against the EGFR protein. The in silico ADMET predicted T-1-PMPA's safety and general drug-likeness. In vitro experiments demonstrated that T-1-PMPA effectively inhibited EGFRWT and EGFR790m, with IC50 values of 86 and 561 nM, respectively, compared to Erlotinib (31 and 456 nM). T-1-PMPA also showed significant suppression of the proliferation of HepG2 and MCF7 malignant cell lines, with IC50 values of 3.51 and 4.13 µM, respectively. The selectivity indices against the two cancer cell lines indicated the overall safety of T-1-PMPA. Flow cytometry confirmed the apoptotic effects of T-1-PMPA by increasing the total percentage of apoptosis to 42% compared to 31, and 3% in Erlotinib-treated and control cells, respectively. The qRT-PCR analysis further supported the apoptotic effects by revealing significant increases in the levels of Casp3 and Casp9. Additionally, T-1-PMPA controlled the levels of TNFα and IL2 by 74 and 50%, comparing Erlotinib's values (84 and 74%), respectively. CONCLUSION: In conclusion, our study's findings suggest the potential of T-1-PMPA as a promising apoptotic anticancer lead compound targeting the EGFR.

Dapoxetine versus glans penis injection with hyaluronic acid gel in treatment of premature ejaculation.

Objective: to compare the results of using Dapoxetine and HA (hyaluronic acid) gel injection by Five puncture technique in the treatment of premature ejaculation (PE). Methods: 100 sexually active heterosexuals circumcised males with lifelong PE were included in the study. Group A patients were treated with on-demand Dapoxetine, while group B was treated with HA gel glans penis injection using a five-puncture technique. Both groups were evaluated at 1st,3rd and 6th months post-treatment using IELT. Results: There were no significant differences between both groups regarding patient demographic. Mean pretreatment IELT in groups A and B were 45.82 ± 7.44 and 46.18 ± 7.82 receptively. There was no significant difference between both groups. After treatment, both groups show significant ILET improvement during the 1st,3rd, and 6th months follow-up with a P value < 0.001. However, when comparing the improvement of ILET in group A (Dapoxetine) and group B (HA injection), there were high significance differences in favor of group B in the 1st,3rd, and 6th-month follow-up. Conclusion: Although both treatment modalities have improved IELT and premature ejaculation, but HA injection with five punctures technique was significantly better than oral Dapoxetine with self-limited side effects.

Evaluating the Effect of TeamSTEPPS on Teamwork Perceptions and Patient Safety Culture among Newly Graduated Nurses.

BACKGROUND: Quality healthcare delivery is contingent upon effective teamwork and a patient safety-focused culture. TeamSTEPPS offers an evidence-based framework that enhances these competencies. However, the impact of TeamSTEPPS on newly graduated nurses, who undergo a significant transitional phase, has yet to be comprehensively explored. Consequently, the objective of this study was to assess the influence of TeamSTEPPS on perceptions of teamwork and patient safety culture among newly graduated nurses. METHODS: This study employed a quasi-experimental pretest-posttest design with a single group, utilizing a convenience sample of 132 newly recruited nurses from a university hospital. The participants completed the hospital survey on patient safety culture and the TeamSTEPPS teamwork perceptions questionnaire at three different time points. RESULTS: The impact of the TeamSTEPPS training program was found to be significant, as indicated by the substantial improvement in the mean scores of nurses' perceptions regarding teamwork and the culture of patient safety across multiple assessments (p < 0.001). The effect size (η2p ≥ 0.14) suggests a large effect, further emphasizing the meaningful impact of the program on the measured outcomes. CONCLUSIONS: The study underscores the effectiveness of TeamSTEPPS as a valuable framework for facilitating the seamless transition of newly graduated nurses into the healthcare field. Integrating TeamSTEPPS into nursing training programs can significantly enhance nurses' perceptions of teamwork and the culture of patient safety. Therefore, it is crucial for nurse managers to implement TeamSTEPPS systematically, aiming to improve teamwork perception and cultivate a patient safety culture among nurses. Furthermore, they should establish mechanisms to ensure the consistent application of these skills over time.

Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC-MS/MS cancer cell entrapment assays.

Directly acting antivirals (DAAs) are a breakthrough in the treatment of HCV. There are controversial reports on their tendency to induce hepatocellular carcinoma (HCC) in HCV patients. Numerous reports have concluded that the HCC is attributed to patient-related factors while others are inclined to attribute this as a DAA side-effect. This study aims to investigate the effect of polymerase inhibitor DAAs, especially daclatasivir (DLT) on cellular proliferation as compared to ribavirin (RBV). The interaction of DAAs with variable cell-cycle proteins was studied in silico. The binding affinities to multiple cellular targets were investigated and the molecular dynamics were assessed. The in vitro effect of the selected candidate DLT on cancer cell proliferation was determined and the CDK1 inhibitory potential in was evaluated. Finally, the cellular entrapment of the selected candidates was assessed by an in-house developed and validated LC-MS/MS method. The results indicated that polymerase inhibitor antiviral agents, especially DLT, may exert an anti-proliferative potential against variable cancer cell lines. The results showed that the effect may be achieved via potential interaction with the multiple cellular targets, including the CDK1, resulting in halting of the cellular proliferation. DLT exhibited a remarkable cell permeability in the liver cancer cell line which permits adequate interaction with the cellular targets. In conclusion, the results reveal that the polymerase inhibitor (DLT) may have an anti-proliferative potential against liver cancer cells. These results may pose DLT as a therapeutic choice for patients suffering from HCV and are liable to HCC development.

New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies.

BACKGROUND: VEGFR-2 has emerged as a prominent positive regulator of cancer progression. AIM: Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2. METHODS: Design and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay. In silico investigations including docking, MD simulations, ADMET, toxicity, and DFT studies were performed. RESULTS: Compound 15 showed the strongest VEGFR-2 inhibitory activity with an IC50 value of 0.066 µM. Additionally, most of the synthesized compounds showed anti-proliferative activity against HepG2 and MCF-7 cancer cell lines at the micromolar range with IC50 values ranging from 0.04 to 4.71 µM, relative to sorafenib (IC50 = 2.24 ± 0.06 and 3.17 ± 0.01 µM against HepG2 and MCF-7, respectively). Also, compound 15 showed selectivity indices of 1.36 and 2.08 against HepG2 and MCF-7, respectively. Furthermore, compound 15 showed a significant apoptotic effect and arrested the cell cycle of MCF-7 cells at the S phase. Moreover, compound 15 had a significant inhibitory effect on the ability of MCF-7 cells to heal from. Docking studies revealed that the synthesized thiazolidine-2,4-diones have a binding pattern approaching sorafenib. MD simulations indicated the stability of compound 15 in the active pocket of VEGFR-2 for 200 ns. ADMET and toxicity studies indicated an acceptable pharmacokinetic profile. DFT studies confirmed the ability of compound 15 to interact with VEGFR-2. CONCLUSION: Compound 15 has promising anticancer activity targeting VEGFR-2 with significant activity as an apoptosis inducer.