Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma.

Glioblastoma multiforme (GBM) is the most aggressive type of glioma and is often resistant to traditional therapies. Evidence suggests that glioma stem cells (GSCs) contribute to this resistance. Mithramycin (Mit-A) targets GSCs and exhibits antitumor activity in GBM by affecting transcriptional targets such as SRY-related HMG-box transcription factor 2 (SOX2), oligodendrocyte lineage transcription factor 2 (OLIG2), and zinc finger E-box binding homeobox 1 (ZEB1). However, its clinical use has been limited by toxicity. This study explored the diagnostic potential of serum extracellular vesicles (EVs) to identify Mit-A responders. Serum EVs were isolated from 70 glioma patients, and targeted gene expression was analyzed using qRT-PCR. Using chemosensitivity assay, we identified 8 Mit-A responders and 17 nonresponders among 25 glioma patients. The M-score showed a significant correlation (p = 0.045) with isocitrate dehydrogenase 1 mutation but not other clinical variables. The genes SOX2 (p = 0.005), OLIG2 (p = 0.003), and ZEB1 (p = 0.0281) were found to be upregulated in the responder EVs. SOX2 had the highest diagnostic potential (AUC = 0.875), followed by OLIG2 (AUC = 0.772) and ZEB1 (AUC = 0.632).The combined gene panel showed significant diagnostic efficacy (AUC = 0.956) through logistic regression analysis. The gene panel was further validated in the serum EVs of 45 glioma patients. These findings highlight the potential of Mit-A as a targeted therapy for high-grade glioma based on differential gene expression in serum EVs. The gene panel could serve as a diagnostic tool to predict Mit-A sensitivity, offering a promising approach for personalized treatment strategies and emphasizing the role of GSCs in therapeutic resistance.

In-utero Diagnosis of Prostatic Embryonal Rhabdomyosarcoma.

Though rhabdomyosarcoma is the most common soft-tissue tumor diagnosed in children there are no reported cases of prenatally detected prostatic embryonal rhabdomyosarcoma. This report demonstrates the first reported case of this phenomenon and its subsequent workup, diagnosis, and treatment.

Resveratrol for dry eye disease - Hope or Hype?

Dry eye disease (DED) is a multifactorial and common ophthalmic disease that has a tremendous effect on the quality of life. It is now becoming a public health concern because of our changing lifestyle and environment. The current treatment modalities, artificial tear substitutes, and anti-inflammatory therapy are directed at dry eye symptoms. One of the major drivers for DED is oxidative stress, and the polyphenol group of natural compounds has the potential to reduce the same. Resveratrol, widely found in the skin of grapes and nuts, has antioxidative and anti-inflammatory properties. It has been shown to have beneficial effects in glaucoma, age-related macular degeneration, retinopathy of prematurity, uveitis, and diabetic retinopathy. Studies have also explored the beneficial effects of resveratrol in DED, making it as a promising therapeutic molecule. Resveratrol has not yet reached clinical application because of difficulty in deliverability and low bioavailability. In this review, we explore the potential of resveratrol in DED treatment based on various in vitro and in vivo studies.

Effect of Prostate Volume and Minimum Tumor Temperature on 4-Year Quality-of-Life After Focal Cryoablation Compared with Active Surveillance in Men with Prostate Cancer.

Background: The purpose of this study is to analyze quality-of-life (QoL) metrics in men treated with focal cryoablation (FC) compared with active surveillance (AS) for localized prostate cancer over a 4-year follow-up period. We further investigated the effect of prostate size and minimum tumor temperature on QoL outcomes. Methods: An Institutional Review Board-approved database was reviewed for patients who underwent FC or AS. QoL questionnaire responses were collected and scores were analyzed for differences between FC and AS, between prostate volume <50 cc and ≥50 cc, and "cold" (<-78°C) and "warm" (≥-78°C) tumor temperatures. Results: One hundred forty-eight AS and 60 FC patients were included. Compared with AS, no significant difference existed in urinary function (UF) measured by Expanded Prostate Cancer Index Composite (EPIC) (p = 0.593) and International Prostate Symptom Score (IPSS) (p = 0.241), bowel habits (p = 0.370), or anxiety (p = 0.672) across time post-FC. FC had significantly worse sexual function (SF) compared with AS measured by EPIC (p < 0.0001) and International Index of Erectile Function (IIEF) (p < 0.0001). Patients with prostate volume <50 cc did not demonstrate differences between AS and FC in UF on EPIC (p = 0.459) or IPSS (p = 0.628), but FC patients had worse SF on EPIC (p < 0.001) and IIEF (p < 0.001). FC patients with a prostate volume ≥50 cc had better UF measured by IPSS (p < 0.05) and similar SF on EPIC (p = 0.162) and IIEF (p = 0.771) compared with AS. UF over time measured by EPIC (0.825) and IPSS (p = 0.658) was the same between AS, "warm," and "cold" FC groups. AS had significantly better SF than the "warm" and "cold" FC groups on EPIC (p < 0.001) and IIEF (p < 0.05). Conclusions: No differences were found in anxiety, urinary, or bowel function between AS and FC. Despite differences in SF, patients with larger prostates had no difference in SF and improved UF compared with AS. Future studies with larger cohorts are needed.

Capillary hemangioma of the bladder in a pediatric patient.

We report a case of a bladder hemangioma in a pediatric patient. A 2-year-old Caucasian female presented with intermittent gross hematuria and protrusion of beefy red tissue near the vaginal introitus when straining. On cystoscopy, we discovered a wide-based vermiform mass. Transurethral resection of the bladder mass was performed. Based on the histological findings of the tissue resected, a diagnosis of capillary hemangioma of the bladder was made. Despite their rarity, bladder hemangiomas should be considered in the differential in children with gross hematuria.

Postnatal expression of the lysine methyltransferase SETD1B is essential for learning and the regulation of neuron-enriched genes.

In mammals, histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Among these enzymes, SETD1B (SET domain containing 1b) has been linked to syndromic intellectual disability in human subjects, but its role in the mammalian postnatal brain has not been studied yet. Here, we employ mice deficient for Setd1b in excitatory neurons of the postnatal forebrain, and combine neuron-specific ChIP-seq and RNA-seq approaches to elucidate its role in neuronal gene expression. We observe that Setd1b controls the expression of a set of genes with a broad H3K4me3 peak at their promoters, enriched for neuron-specific genes linked to learning and memory function. Comparative analyses in mice with conditional deletion of Kmt2a and Kmt2b histone methyltransferases show that SETD1B plays a more pronounced and potent role in regulating such genes. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B-dependent regulation of H3K4me levels in postnatal neurons is critical for cognitive function.

Kidney Autotransplantation for Treatment of Ureteric Obstruction: A Case Report and Brief Review of the Literature.

Autologous kidney transplantation is a relatively rare procedure that has been used as an alternative treatment for a variety of complex genitourinary problems, in particular for the treatment of complex proximal ureteral strictures. In this case report, a 47-year-old male, who had undergone a living donor nephrectomy 14 years earlier, presented with episodes of acute kidney injury on chronic kidney disease. He was found to have a complex proximal ureter stricture of his solitary right kidney. He underwent nephrectomy with subsequent autotransplantation of the kidney into the right iliac fossa. His renal function improved significantly after surgery. Renal autotransplantation may be considered for the management of proximal ureteral obstruction when alternative options are contraindicated.

Treatment of obstructive sleep apnea does not treat primary nocturnal enuresis.

INTRODUCTION: Primary Nocturnal Enuresis (PNE), obesity, and obstructive sleep apnea (OSA) are suggested to share a complex interaction whereby risk for PNE is increased when obesity and airway obstruction are present. We aimed to evaluate whether surgical or medical management of OSA in the treatment of patients with PNE and improves PNE outcomes. STUDY DESIGN: Our institutions electronic medical record was queried for patients who underwent a pediatric diagnostic polysomnogram (PDPSG) for the complaint of PNE between October 2010 and September 2020 and were diagnosed with OSA. Retrospective chart review was performed of the 59 patients identified. Patients were divided based on therapy type for their OSA. Groups included those no therapy, any therapy which includes patients undergoing tonsillectomy and adenoidectomy (T&A) and/or continuous positive airway pressure (CPAP) and those who chose T&A. Primary outcome was to evaluate effects of treating OSA with T&A and effects on PNE outcome based on International Children's Continence Society (ICCS) definitions of complete, partial or no improvement. Separate grouping based on ICCS PNE outcome were also made for evaluation of variables associated with each group. Secondary outcome evaluated role of BMI in success of treatments of PNE. Chi-squared and one-way ANOVA tests were performed. RESULTS: 59 patients (64.4% male, mean age at diagnosis 8.8 years old) underwent a PDPSG for PNE. Monosymptomatic PNE was diagnosed in 40.7% while 32.2% had non-monosymptomatic PNE and the remainder were unknown. Patients were predominantly Caucasian (47.5%), with an average BMI of 20.6 kg/m2 25 patients underwent no therapy for their OSA while the remaining 34 received treatment. No statistically significant difference between those receiving and those forgoing therapy were noted in age, race, gender, BMI, type of PNE or Apnea-Hypopnea Index. There was also so significant difference in ICCS defined enuresis outcomes (p = 0.871) with over 60% in both groups experiencing resolution or improvement. Follow up was significantly different between cohorts, measured at 43 months for those receiving therapy for OSA and 29.1 months for those forgoing therapy. When considering only those who chose T&A as their therapy for PNE, there were once again, no significant differences between groups including ICCS enuresis outcome. Sub-grouping based on ICCS enuresis outcome revealed no associations between variables measured and improvement of PNE (p > 0.05), other than defining type of PNE (p = 0.012). CONCLUSION: In patients with OSA and PNE, surgical treatment of airway obstruction had no effect on resolution of PNE.

Management of Testicular Torsion and a Contralateral Testicular Mass Presenting Synchronously.

Testicular masses found in prepubertal males are often benign in nature. This has led to an increase in the use of testis-sparing surgery. Testicular torsion is considered a urologic emergency that requires immediate surgical intervention. Based off literature review, it is rare for these unique entities to present synchronously in a single patient. This report demonstrates that in the pediatric population it is possible to safely treat a suspected benign testicular mass with testis sparing mass enucleation if it presents synchronously with testicular torsion in the contralateral testis.

Trends in treatment of cT1 penile cancer: Analysis of the National Cancer Database.

OBJECTIVE: To characterize the treatment trends and outcomes in clinical stage T1 penile cancer using the National Cancer Database (NCDB). METHODS: The National Cancer Database was queried for all men with cT1 penile cancer from 2004 to 2015. Patients were categorized as cT1a or cT1b. Treatment was categorized as no treatment, local therapy (including penile sparing therapies), partial penectomy, or radical penectomy. Trends in treatment were analyzed over time and in correlation with stage and demographic variables. Stage and treatment type were evaluated in respect to pathological outcomes and survival. RESULTS: A total of 2,484 men were identified with cT1 penile cancer, 90.1% of which had cT1a disease. The most common treatments were local therapy for cT1a and partial penectomy for cT1b. Over the time period studied, use of local therapy decreased while use of partial or radical penectomy increased. Patients treated at low volume facilities were more likely to undergo no treatment (8.0% vs. 6.5% in high volume) or local therapy (49.9% vs. 41.5% in high volume, P < 0.001). Local therapy was associated with increased risk of positive margin (odds ratio 4.7, P < 0.001) and positive margin was associated with a trend toward decreased overall survival (P = 0.07). CONCLUSIONS: In the past decade, there has been decreased use of local therapy and increased use of partial or radical penectomy in cT1 penile cancer. Men treated at low volume facilities are more likely to be treated with local therapy which is associated with increased rates of positive margins and may also be associated with a trend toward decreased overall survival. Centralization of care in T1 penile cancer may lead to improved outcomes.

Creutzfeldt-Jakob Disease Presenting as Posterior Reversible Encephalopathy Syndrome.

Creutzfeldt-Jakob disease (CJD) is the most common human prion disease presenting with subacute cognitive decline. Common MRI findings for CJD include the T2 prolongation signal of the putamen and head of caudate. Diffusion-weighted MRI (DW-MRI) is considered to be the most sensitive technique for the detection of CJD-related abnormalities, especially for cortical changes. We report the case of a 77-year-old female who presented with dizziness, visual hallucination, and a rapid decline in her mental state shortly after a right knee surgery. Brain MRI with contrast showed cortical and subcortical T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities in bilateral posterior temporal lobes and the left occipital lobe without an associated enhancement, suggestive of posterior reversible encephalopathy syndrome (PRES). Workup including metabolic, infectious, and vasculitic panels were all within normal limits. A few days later, she developed persistent myoclonus, and a continuous electroencephalogram (EEG) revealed multifocal epileptiform and generalized discharges, forming multifocal periodic discharges and generalized periodic discharges (GPDs). Cerebrospinal fluid (CSF) analysis was positive for 14-3-3 and elevated T-tau protein consistent with a diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). This is a rare case of CJD presenting with a brain MRI resembling PRES. CJD may have various features on MRI, and a high degree of suspicion is required to confirm the diagnosis.

Paclitaxel Encapsulation into Dual-Functionalized Multi-Walled Carbon Nanotubes.

This work reports the synthesis of multi-walled carbon nanotubes (CNTs) from xylene/ferrocene using catalytic chemical vapor deposition technique. Following characterization using transmission electron microscopy (TEM), energy-dispersive X-ray (EDX), and Raman spectroscopy, CNT surface was dual-functionalized using ethylenediamine and phenylboronic acid groups. Average diameter of CNTs was calculated to be 16.5 nm. EDX spectra confirmed the existence of carbonaceous deposits on the tube's surface. Scattered electron diffraction and X-ray peak broadening calculations showed consistent inter-planer distance of the grown CNTs. Chemical functionalization, confirmed from FT-IR and Raman spectra, showed an enhanced dispersibility of CNTs in water. We describe the changes in the first- and second-order regions of the Raman spectra following the encapsulation of an anti-cancer drug, paclitaxel (PLX), into the free volume of functionalized CNTs. High PLX loading, achieved through its non-covalent π-π stacking within the CNT interior, is confirmed through the blue-shifted, softened G band in the Raman spectrum. While not addressed here, we will exploit this dual functionalization tactic to elaborate the relative role of attached moieties in the affinity interaction of CNTs with extra-cellular sialic acid, a biological target showing metastatic stage-dependent over-expression in colon cancer cells.