Caging Bioactive Triarylimidazoles: An Approach to Create Visible Light-Activatable Drugs.

Imidazoles are crucial structural components in a variety of small-molecule inhibitors designed to target different kinases in anticancer treatment. However, the effectiveness of such inhibitors is often hampered by nonspecific effects and the development of resistance. Photopharmacology provides a compelling solution by enabling external control over drug activity with spatiotemporal precision. Herein, we introduce a novel strategy for caging bioactive triarylimidazole-based drug molecules. This approach involves introducing a dialkylamino group as a photoremovable group on the carbon atom of the imidazole ring, which intrinsically modulates the core structure from planar imidazole to tetrahedral 2H-imidazole, enabling the caged compound to be selectively uncaged upon visible light exposure. We applied this innovative caging technique to SB431542, a triarylimidazole-based small-molecule inhibitor that targets the pivotal TGF-ß signaling pathway, the dysregulation of which is linked to several human diseases, including cancer. Our results demonstrated the selective inhibition of human breast cancer cell migration in vitro upon light activation, highlighting the potential of our approach to transform triarylimidazole-based drug molecules into visible light-activatable drugs, thereby facilitating spatiotemporal regulation of their pharmacological activity.

Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

PURPOSE: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. METHODS: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. RESULTS: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. CONCLUSION: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown.

Surgical Treatment of Scaphoid Fractures: Recommendations for Management.

Background: Several operative treatments exist for scaphoid fractures, varying by approach (e.g., ercutaneous, volar, or dorsal), implant type (e.g., screw or Kirschner wire), and bone raft choice (e.g., none, nonvascularized, or vascularized). Many previous systematic eviews and meta-analyses have investigated outcomes following different surgicalÚpproaches, the use of vascularized versus nonvascularized bone graft for scaphoidßracture nonunions, and treatment for specific fracture patterns. However, given the advancements n scaphoid fracture treatment in recent years, there is a need for updated treatment recommendations hat would be beneficial to hand surgeons. Purpose: We present a comprehensive review of the operative treatment of scaphoid fractures based on recent literature and propose a unified treatment algorithm for managing these fractures. Methods: The English-language literature was searched from 2002 to 2023 for high evidence level (e.g., randomized trials), review, and meta-analysis articles with the following search terms: "scaphoid, "u8220"scaphoid" AND "nonunion, " and "scaphoid" AND "malunion. " Each article was creened by the authors to determine the scaphoid fracture scenario addressed and ubsequent treatment recommendations. The findings from article reviews were then rganized by scaphoid fracture types in this manuscript. Results: A total of 95 pertinent articles were ultimately selected and used as the basis for reviewing different scaphoid fracture scenarios. A treatment algorithm was then proposed based on literature review. Conclusion: This summary of the recent literature can guide hand surgeons in addressing scaphoidßractures. Future research in scaphoid fracture treatment, particularly for nonunions, would be most beneficial n the form of systematic review, meta-analysis, or multicenter prospective randomized clinical trials. Level of Evidence: IV.

Multi-modal imaging for the detection of early keratoconus: a narrative review.

Keratoconus is a common progressive corneal disorder that can be associated with significant ocular morbidity. Various corneal imaging techniques have been used for the diagnosis of established cases. However, in the early stages of the disease, which include subclinical keratoconus and forme fruste keratoconus, detection of such cases can be challenging. The importance of detecting such cases is very important because early intervention can halt disease progression, improve visual outcomes and prevent postrefractive surgery ectasia associated with performing corneal refractive procedures in such patients. This narrative review aimed to examine several established and evolving imaging techniques for the detection of early cases of keratoconus. The utilization of combinations of these techniques may further increase their diagnostic ability.

Nuclear Cardiology in the Era of Precision Medicine: Tailoring Treatment to the Individual Patient.

Nuclear cardiology, employing advanced imaging technologies like positron emission tomography (PET) and single photon emission computed tomography (SPECT), is instrumental in diagnosing, risk stratifying, and managing heart diseases. Concurrently, precision medicine advocates for treatments tailored to each patient's genetic, environmental, and lifestyle specificities, promising a revolution in personalized cardiovascular care. This review explores the synergy between nuclear cardiology and precision medicine, highlighting advancements, potential enhancements in patient outcomes, and the challenges and opportunities of this integration. We examined the evolution of nuclear cardiology technologies, including PET and SPECT, and their role in cardiovascular diagnostics. We also delved into the principles of precision medicine, focusing on genetic and molecular profiling, data analytics, and individualized treatment strategies. The integration of these domains aims to optimize diagnostic accuracy, therapeutic interventions, and prognostic evaluations in cardiovascular care. Advancements in molecular imaging and the application of artificial intelligence in nuclear cardiology have significantly improved the precision of diagnostics and treatment plans. The adoption of precision medicine principles in nuclear cardiology enables the customization of patient care, leveraging genetic information and biomarkers for enhanced therapeutic outcomes. However, challenges such as data integration, accessibility, cost, and the need for specialized expertise persist. The confluence of nuclear cardiology and precision medicine offers a promising pathway toward revolutionizing cardiovascular healthcare, providing more accurate, effective, and personalized patient care. Addressing existing challenges and fostering interdisciplinary collaboration is crucial for realizing the full potential of this integration in improving patient outcomes.

Penile reconstruction after complete bladder exstrophy repair.

INTRODUCTION: The decreased penile length in patients born with bladder exstrophy (BE) results partly from pubic symphysis diastasis and the separation of the corporal bodies. Also, intrinsic shortening of anterior corporal compartment, residual penile dorsal curvature, and postsurgical scarred skin share in creation of short penile length. OBJECTIVE: The goal of this study was to look at whether adult men who had bladder exstrophy (BE) surgery as babies needed and benefited from penile reconstruction, which included penile lengthening and repair of any redo penile pathology that was present at the same time. STUDY DESIGN: We reviewed the records of 31 repaired BE patients with mean age of 21.4 ± 3.7 years. The patients complained of their dissatisfaction with short penile length, residual dorsal penile curvature, distal dorsal or hypospadiac urethral opening and scared penopubic skin. The penile lengthening was performed by sub-periosteal detachment of the corporal bodies from the pubic rami in all cases. In 8 patients full thickness dermal grafts were used to penile resurfacing after its lengthening. Twelve patients underwent coronal or glanular urethroplasty. Phalloplasty was performed in one patient using forearm free graft. RESULTS: Subjective evaluation by the patient reported satisfactory results in 25/31 (80.6 %). The degree of penile lengthening measured at 6 months and one year postoperatively showed increased length which varied between 50 % and 150 % of the preoperative penile length. DISCUSSION: We hypothesize that congenital causes, such as short anterior corporeal compartment, wide pubic rami diastasis, and short penile urethra, as well as iatrogenic causes, such as post-surgical peno-pubic scars, could account for the coexisting multifactorial causes of penile shortening in male adults with BE. Penile lengthening is permitted, in our opinion, provided that the crura from the pubic rami is carefully and partially mobilized. CONCLUSIONS: The short phallus, residual dorsal chordee and distal urethroplasty can be corrected successfully in the majority of patients. Adult males with BE may have short penis that requires another reconstructive stage. The short phallus, residual chordee and distal urethroplasty can be corrected` successfully in the majority of patients.

Pseudo-Luciferase Activity of the SARS-CoV-2 Spike Protein for Cypridina Luciferin.

Enzymatic reactions that involve a luminescent substrate (luciferin) and enzyme (luciferase) from luminous organisms enable a luminescence detection of target proteins and cells with high specificity, albeit that conventional assay design requires a prelabeling of target molecules with luciferase. Here, we report a luciferase-independent luminescence assay in which the target protein directly catalyzes the oxidative luminescence reaction of luciferin. The SARS-CoV-2 antigen (spike) protein catalyzes the light emission of Cypridina luciferin, whereas no such catalytic function was observed for salivary proteins. This selective luminescence reaction is due to the enzymatic recognition of the 3-(1-guanidino)propyl group in luciferin at the interfaces between the units of the spike protein, allowing a specific detection of the spike protein in human saliva without sample pretreatment. This method offers a novel platform to detect virus antigens simply and rapidly without genetic manipulation or antibodies.

The Potential of Salivary Biomarkers in Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a formidable global health concern with a dire prognosis, highlighting the critical need for early detection strategies. This systematic review delves into the potential of salivary biomarkers as a non-invasive means for identifying PDAC at its incipient stages. Saliva's proximity to the circulatory system enables the detection of tumor-derived biomolecules, making it an ideal candidate for mass screening. The analysis of three selected studies reveals promising candidates such as Neisseria mucosa, Fusobacterium periodonticum, polyamines, and specific long non-coding RNAs (lncRNAs). Notably, polyamines like spermine show potential in distinguishing PDAC, while lncRNAs HOX transcript antisense RNA (HOTAIR) and plasmacytoma variant translocation 1 (PVT1) exhibit superior sensitivity and specificity compared to traditional serum markers. However, challenges, including small sample sizes and a lack of validation, underscore the need for standardized diagnostic panels and large-scale collaborative studies. Advancements in nanotechnology, machine learning, and ethical considerations are crucial for harnessing the diagnostic potential of saliva. The review emphasizes the imperative for extensive clinical trials to validate salivary biomarkers, ensuring not only diagnostic accuracy but also cost-effectiveness, patient compliance, and long-term benefits in the realm of PDAC screening. Longitudinal studies are recommended to unravel temporal changes in salivary biomarkers, shedding light on disease progression and treatment response.

The Effect of Various Preparation and Cementation Techniques of Dental Veneers on Periodontal Status: A Systematic Review and Meta-Analysis.

Dental veneers are widely used to restore or/and enhance dental aesthetics. However, it is not well understood how various veneer preparation and cementation methods affect periodontal health. To provide a quantitative estimate of the overall effect size of the intervention, this study was conducted to synthesize the available evidence on the impact of various dental veneer preparation and cementation methods on periodontal status. A thorough search strategy was implemented using Medical Subject Headings keywords and Boolean operators across various major databases, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Nine papers were ultimately selected for inclusion in the review. Seven studies demonstrated a positive impact of dental veneers on overall periodontal health, while two studies reported a slight worsening. The forest plot analyses showed a somewhat protective effect of dental veneers on periodontal health, with odds ratio of 0.18 and relative risk of 0.34, suggesting that dental veneers may have a positive impact on overall periodontal health. The current study, with considerable heterogeneity among the studies, indicates that dental veneers are associated with an overall positive effect on the periodontal health. However, given the variations in study designs, sample sizes, and follow-up times, additional research may be required to confirm and generalize these results.

Short-Term and Long-Term Impact of COVID-19 on Quality of Life and Psychological Outcomes in Saudi Arabia: A Comparative Cross-Sectional Study.

Background: Prior research has revealed notable declines in health-related quality of life (HRQoL) and substantial psychological impacts among individuals infected with COVID-19. However, there is a noticeable gap in studies addressing the enduring long-term effects of COVID-19 on HRQoL and psychological well-being. Objective: The current study investigated and compared short and long-term effects of COVID-19 on HRQoL and psychological outcomes among the Saudi population. Methods: The Arabic version of the SF-36 questionnaire was used to assess HRQoL while Anxiety and depression were evaluated by the Hamilton Anxiety (HAM-A) and Depression Scales (HDRS). Participants (n=292) were categorized into three groups: the "never-been-infected" group (n=134), the "one-year infected group" (n=43), and the "more than one year infected" group (n=115). Descriptive statistics were presented using numerical values and frequencies. To compare the groups, a one-way analysis of variance (ANOVA) test was used. Results: Most SF-36 domains exhibited lower values while HAM-A and HDRS values were higher in individuals infected during last year compared to those who never infected. Social functioning subscale of the SF-36 showed a significant difference between the groups (F (2.289) = 6.094, p = 0.01) and the effect size was d = 0.95. Pairwise comparison showed a significant reduction in the social functioning component of SF-36 in "one-year group" compared to both groups "never-been-infected" group (mean difference -13.58 (4.40-22.76) p < 0.01) and "more than one year infected" group (mean difference -10.80 (1.44-20.16) p = 0.02). HAM-A and HDRS scores showed mild levels of anxiety (<17 score) and depression (8 to 16 score) in all groups. Conclusion: The influence of COVID-19 on psychological well-being and HRQoL is significant regardless of whether individuals infected with the virus. Overall, the consistent presence of mild anxiety and depression across all groups highlights the need for a holistic approach to mental health.

Plasma S1P Orchestrates the Reverse Transendothelial Migration of Aortic Intimal Myeloid Cells in Mice.

BACKGROUND: Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into the arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood. S1P (sphingosine-1-phosphate) is a lipid mediator that regulates immune cell trafficking by signaling via 5 G-protein-coupled receptors (S1PRs [S1P receptors]). We investigated the role of S1P in the RTM of aortic intimal MCs. METHODS: Intravenous injection of lipopolysaccharide was used to model a systemic inflammatory stimulus that triggers RTM. CD11c+ intimal MCs in the lesser curvature of the ascending aortic arch were enumerated by en face confocal microscopy. Local gene expression was evaluated by transcriptomic analysis of microdissected intimal cells. RESULTS: In wild-type C57BL/6 mice, lipopolysaccharide induced intimal cell expression of S1pr1, S1pr3, and Sphk1 (a kinase responsible for S1P production). Pharmacological modulation of multiple S1PRs blocked lipopolysaccharide-induced RTM and modulation of S1PR1 and S1PR3 reduced RTM in an additive manner. Cre-mediated deletion of S1pr1 in MCs blocked lipopolysaccharide-induced RTM, confirming a role for myeloid-specific S1PR1 signaling. Global or hematopoietic deficiency of Sphk1 reduced plasma S1P levels, the abundance of CD11c+ MCs in the aortic intima, and blunted lipopolysaccharide-induced RTM. In contrast, plasma S1P levels, the abundance of intimal MCs, and lipopolysaccharide-induced RTM were rescued in Sphk1-/- mice transplanted with Sphk1+/+ or mixed Sphk1+/+ and Sphk1-/- bone marrow. Stimulation with lipopolysaccharide increased endothelial permeability and intimal MC exposure to circulating factors such as S1P. CONCLUSIONS: Functional and expression studies support a novel role for S1P signaling in the regulation of lipopolysaccharide-induced RTM and the homeostatic maintenance of aortic intimal MCs. Our data provide insight into how circulating plasma mediators help orchestrate intimal MC dynamics.

The long-term consequences of the hypospadias salvage repair issue.

PURPOSE: To present the long-term results of redo-hypospadias at our tertiary referral center following a failed prior repair. METHODS: One hundred sixty-four individuals with a history of unsuccessful repairs qualified for our retrospective cohort study. Our inclusion criteria were as follows: pre-operative data that was accessible, redo-hypospadias that was successfully repaired, and at least three years of follow-up at the last hospital visit. RESULTS: The mean patient age was 91.3 ± 21.1 months. The mean follow-up after successful repair was 41.3 ± 3.1 months. Ninety-two (group A) had one prior repair, and 72 (group B) had 2 or 3 repairs. Group A underwent six primary techniques: 32 underwent Onlay Island Flap (OIF), 10 underwent Mathieu, 12 underwent Tubularized Incised Plate Urethroplasty (TIPU), 8 underwent Urethral Mobilization (UM), and 34 underwent Buccal Mucosal Graft (BMG) { dorsal inlay Graft Urethroplasty (DIGU) in 4 and staged BMG in 30 patients}. In group B, four procedures were used: TIPU in 4, UM in 6, and BMG in 62 (staged BMG in 50 cases and DIGU in 12). CONCLUSIONS: The selected type of repair will depend on many factors, like residual healthy local skin and expertise. Safe techniques for repair of redo hypospadias after its 1st failure include TIPU, Mathieu, UM, OIF, and DIGU for distal varieties. After 2nd or 3rd repair DIGU, UM, and TIPU can be performed in distal types, while staged BMG can be applied for proximal ones.

Spatial congruency or discrepancy? Exploring the spatiotemporal dynamics of built-up expansion patterns and flood risk.

Most coastal cities have been experiencing unprecedented urbanization-induced flood risk, climatic events, and haphazard anthropogenic activities, jeopardizing residents' lives and building environments. Despite mounting flood-related studies, analyzing the correlation between the spatiotemporal dynamics of Built-up Expansion patterns (BE) and flood risk remains unknown and holds divergent perspectives. In this context, the coastal city of Alexandria, Egypt, characterized by multiple urban patterns and experiencing heavy rainfall annually, was selected as a testbed. Our method defined the spatiotemporal rates of BE from 1995 to 2023, quantified flood risk spatially, and finally investigated the correlation between BE and flood risk through spatial and statistical analysis. Our results show the built-up area occupied 30.32 % of the total city area till 2023, and the infilling pattern dominated the BE growth by 45.21 % of the total built-up area, followed by leapfrogging and edge expansion by 33.25 % and 21.55 %, respectively. The unplanned-infilling pattern is predominantly highly correlated with the flood-vulnerable peaks (correlation coefficient (rk) = 0.975, p-value < 0.05) and lowers dramatically towards planned-infilling regions with flood protections. Meanwhile, a spatial mismatch exists between high-risk peaks and leapfrogging and edge expansion (rk = 0.118 and 0.662, respectively, with a p-value < 0.01), indicating that controlling the built-up amount is inadequate for mitigating flood risk. Porosity-based urban configuration and spatial distribution of built-up patches in harmony with nature-based solutions are recommended for shaping flood-resilient and effective urban planning.

The Effect of Visual Impairment and Its Severity on Vision-Related and Health-Related Quality of Life in Jordan: A Comparative Cross-Sectional Study.

Purpose: To assess the effect of visual impairment (VI), its severity, and ocular diseases on vision-related and health-related quality of life (QoL) in Jordan. Patients and Methods: A comparative, cross-sectional, hospital-based study was conducted among a group of 278 patients with VI aged ≥ 18 years, and age and sex-matched control group of 278 individuals with no VI. An interviewer administered the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) to all participants. Results: All the mean VFQ-25 subscales scores, physical component scale (PCS) and the mental component scale (MCS) of the SF-12 were significantly lower in patients with VI compared to controls with no VI. The VFQ-25 subscales (except general health and ocular pain), PCS, and MCS scores significantly decreased with more severity of VI. In the adjusted multivariate analysis, lower level of education (p=0.013), male sex (p=0.016), and the presence of cerebrovascular disease (p=0.019) were significantly associated with lower VFQ-25 composite scores in visually impaired patients compared to controls. Ocular disease duration of >5 years and progressive VI were significantly associated with lower VFQ-25 composite scores (p= 0.026 and p<0.001) respectively, in patients with VI. Glaucoma had a significantly larger reduction in mean scores of all the VFQ-25 subscales, and the PCS of the SF-12 compared to all other ocular diseases. Conclusion: Both VI and increasing severity of impairment were associated with reduced vision-related and health-related quality of life in adult Jordanians. Glaucoma patients and less educated people were particularly affected. Routine assessment of QoL in visually impaired patients and improving referral protocols to vision rehabilitation services is recommended to improve the QoL in those patients.

Iron metabolism in autism spectrum disorder; inference through single nucleotide polymorphisms in key iron metabolism genes.

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental problems with various genetic and environmental components. The ASD diagnosis is based on symptom expression without reliance on any biomarkers. The genetic contributions in ASD remain elusive. Various studies have linked ASD with iron. Since iron plays a crucial role in brain development, neurotransmitter synthesis, neuronal myelination and mitochondrial function, we hypothesized that iron dysregulation in the brain could play a role and contribute to the pathogenesis of ASD. In this study, we investigated single nucleotide polymorphisms in ASD in various iron metabolism genes, including the Transferrin Receptor (TFRC) gene (rs11915082), the Solute Carrier Family 11 Member 2 (SLC11A2) gene (rs1048230 and rs224589), the Solute Carrier Family 40 Member 1 (SLC40A1) gene (rs1439816), and hepcidin antimicrobial peptide (HAMP) gene (rs10421768). We recruited 48 patients with ASD and 88 matched non-ASD controls. Our results revealed a significant difference between ASD and controls in the G allele of the TFRC gene rs11915082, and in the C allele of the SLC40A1 gene rs1439816. In silico analysis demonstrated potential positive role of the indicated genetic variations in ASD development and pathogenesis. These results suggest that specific genetic variations in iron metabolism genes may represent part of early genetic markers for early diagnosis of ASD. A significant effect of SNPs, groups (ASD/control) as well as interaction between SNPs and groups was revealed. Follow-up post hoc tests showed a significant difference between the ASD and control groups in rs11915082 (TFRC gene) and rs1439816 (SLC40A1 gene). Backward conditional logistic regression using both the genotype and allele data showed similar ability in detecting ASD using allel model (Nagelkerke R2 = 0.350 p = 0.967; Variables: rs1439816, rs11915082) compared to genotype model (Nagelkerke R2 = 0.347, p = 0.430; Variables: rs1439816 G, rs1439816 C, rs10421768 A). ROC curve showed 54% sensitivity in detecting ASD compared to 47% for the genotype model. Both models differentiated controls with high accuracy; the allele model had a specificity of 91% compared to 92% for the genotype model. In conclusion, our findings suggest that specific genetic variations in iron metabolism may represent early biomarkers for a diagnosis of ASD. Further research is needed to correlate these markers with specific blood iron indicators and their contribution to brain development and behavior.

Decentralized Sensor Fault-Tolerant Control of DC Microgrids Using the Attracting Ellipsoid Method.

System stability deterioration in microgrids commonly occurs due to unpredictable faults and equipment malfunctions. Recently, robust control techniques have been used in microgrid systems to address these difficulties. In this paper, for DC-islanded microgrids that have sensors faults, a new passive fault-tolerant control strategy is developed. The suggested approach can be used to maintain system stability in the presence of flaws, such as faulty actuators and sensors, as well as component failures. The suggested control is effective when the fault is never recognized (or when the fault is not being precisely known, and some ambiguity in the fault may be interpreted as uncertainty in the system's dynamics following the fault). The design is built around a derived sufficient condition in the context of linear matrix inequalities (LMIs) and the attractive ellipsoid technique. The ellipsoidal stabilization idea is to bring the state trajectories into a small region including the origin (an ellipsoid with minimum volume) and the trajectories will not leave the ellipsoid for the future time. Finally, computational studies on a DC microgrid system are carried out to assess the effectiveness of the proposed fault-tolerant control approach. When compared with previous studies, the simulation results demonstrate that the proposed control technique can significantly enhance the reliability and efficiency of DC microgrid systems.

Intramuscular Hemangioma of the Sternocleidomastoid: A Rare Tumor in an Unusual Location.

Intramuscular hemangiomas (IMH) are benign vascular tumors of the skeletal muscles. These tumors are uncommon in the head and neck region and usually affect the trunk and extremities. IMH of the masseter and trapezius muscles have been reported in the head and neck region. However, the sternocleidomastoid is extremely rare. In the current case report, we described a 25-year-old man with a rare case of intramuscular hemangioma involving the sternocleidomastoid muscle and reviewed the relevant literature. Contrast-enhanced computed tomography was initially obtained and showed a slightly hyperdense soft tissue mass. Head and neck magnetic resonance imaging (MRI) demonstrate a well-delineated hyperintense lesion on the T2 sequence suggestive of a soft tissue hemangioma. Subsequently, angioembolization using onyx was performed, followed by surgical excision of the mass under general anesthesia. Histopathological examination of the mass showed vascular proliferation within the skeletal muscles, and fatty tissue with an abundance of capillaries, which are consistent with capillary type intramuscular hemangioma. The patient was followed up in the clinic until the wound healed. Three months after surgery, no recurrence was observed. Preoperative angioembolization contributed to the success of IMH surgery by reducing morbidity, facilitating complete excision, and decreasing the risk of recurrence.

Long term evaluation of continence after complete primary bladder exstrophy repair.

INTRODUCTION: Continence after bladder exstrophy (BE) repair remains a major debatable challenge to pediatric urologists, together with the lack of standard definitions and long-term results in large series. OBJECTIVE: We assessed the long-term urinary continence in 142 toilet-trained cases after one (1-) stage of complete primary repair of bladder exstrophy (CPRE) and consequent procedures to achieve this goal in a single tertiary referral center. STUDY DESIGN: The current retrospective study included 123 boys and 19 girls with BE that were repaired by (1-) stage CPRE. The Mean age at (BE) repair was 9.5 ± 2.6 weeks. Complete penile disassembly (CPD) was used for epispadias repair in 42 (34.1%) and modified Cantwell-Ransley repair (MCR) was used in 81 (65.9%) boys. Bilateral anterior transverse innominate osteotomies (ATIO) were applied in all. Urinary continence was expressed in terms of the dry interval (DI). Continence procedures were afforded if CPRE failed to achieve DI ≥ 3 h (hrs.), those were in the form of endoscopic bladder neck injection (BNI), bladder neck reconstruction (BNR), and bladder neck closure (BNC) with catheterizable stoma. RESULTS: The mean age at follow up was 12.1 ± 5.2 years. DI ≥ 3 h was gained in 23 (16.2%) after CPRE alone, while complementary post-CPRE continence procedures were required to reach this goal in the remaining patients. Deflux injection was reported in 10 (7%), CIC in 8 (5.6%), BNR in 32 (22.5), and BNC with catheterizable stoma alone in 37 (26.1%), or with Charleston pouch in 32 (22.5%). DISCUSSION: We think that ≥3 h DI with voiding represents an appropriate definition of continence after BE repair. According to the results in the current series, we think that successful anatomical closure of BE is achievable, but the functional outcome in terms of continence and its evaluation is tricky. Results of continence were reported to change with age of the child, and it is difficult to evaluate both before toilet training age and long-term follow up. CONCLUSIONS: Long-term follow up of CPRE with bilateral ATIO alone or with BNI results in ≥3 h DI in a few cases; BNR after CPRE can provide a good chance for continence; otherwise, BNC with catheterizable stoma is a valid option.

Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats.

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1ß, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1ß, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.