Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

Long-term complications and outcomes of augmentation cystoplasty in children with neurogenic bladder.

Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.

Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

Eplerenone improves hyperglycemia and sympathetic excitation in chronic renocardiac syndrome in rats.

We aimed to assess the efficacy of eplerenone, a steroidal mineralocorticoid receptor antagonist known to reduce blood pressure and mitigate cardiovascular disease (CVD) progression, in retarding the progression of chronic kidney disease (CKD) and CVD in a rat model of type 4 cardiorenal syndrome (CRS). We grouped rats into four experimental categories: sham surgery, sham treatment with eplerenone, nephrectomy without eplerenone (Nx), and nephrectomy with eplerenone (Nx + EP). For the Nx + EP group, rats received five-sixths nephrectomy, inducing CKD and CVD conditions such as renal hypertension and hyperglycemia, and were then treated with eplerenone (100 mg/kg/day, orally) over 4 weeks after an initial 4-week observation period. Heart rate, blood pressure, blood sugar levels, and sympathetic nerve excitation were monitored biweekly. In addition, assessments of renal and cardiac tissues, including evaluation of renal tubulointerstitial injury, glomerular injury, and cardiomyocyte hypertrophy, were conducted at week 8. Eplerenone administration mitigated CKD and CVD progression in the Nx + EP group, evident by improved blood pressure (217.3 ± 5.4 versus 175.3 ± 5.6), blood sugar (121.8 ± 1.3 versus 145.6 ± 6.0) level, reduced sympathetic nerve excitation, and cardiomyocyte hypertrophy compared to the Nx group. However, renal tubulointerstitial injury, glomerular injury, and cardiovascular dysfunction, which were increased in rats with type 4 CRS, did not show significant changes with eplerenone treatment. Our study demonstrated that eplerenone treatment did not exacerbate type 4 CRS but improved blood pressure, blood sugar levels, sympathetic nerve excitation, and cardiomyocyte hypertrophy in this model.

Catalase Expression Is an Independent Prognostic Marker in Lung Adenocarcinoma.

BACKGROUND/AIM: Lung adenocarcinoma (LUAD) is the deadliest cancer, and approximately 20% of stage I LUAD cases recur after surgical resection due to its high intratumor heterogeneity. Reactive oxygen species (ROS) have been detected in LUAD and are involved in carcinogenesis and tumor progression. Here, a comprehensive analysis was performed to evaluate the effects of antioxidants on the prognosis of LUAD. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) database was used to study the relationship of gene expression of different ROS-scavenging enzymes with the progression and prognosis of LUAD. RESULTS: Using TCGA LUAD datasets, we found that catalase (CAT) expression was significantly down-regulated in LUAD tissues compared to normal tissues, CAT down-regulation differed significantly between different grades of LUAD, low CAT expression was independently correlated with a worse prognosis in LUAD, and the expression of the CAT gene was associated with an inhibition of the "cell cycle". A panel of LUAD cells (CL1-0, CL1-1, CL1-3, and CL1-5), which harbored mutated p53 (R248W), with gradually increasing invasiveness showed a gradual decrease in CAT expression. Silencing of CAT upregulated cell growth in A549 cells, which harbor wild-type p53 and show high CAT expression and was associated with an increase in the expression of BUB1B, PLK1, and PKMYT1. Finally, over 38% (186/490) of LUAD cases with a p53 mutation exhibited significantly lower CAT expression than those with wild-type p53. CONCLUSION: CAT expression is a potent favorable prognostic marker for LUAD and may represent a drug target.

Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT. METHODS: Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT. RESULTS: RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells. CONCLUSIONS: Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.

Interhemispheric Vertical Hemispherotomy: Technique, Outcome, and Pitfalls-A Bicentric Retrospective Case Series of 39 Cases.

BACKGROUND AND OBJECTIVES: When seizure onset affects a whole hemisphere, hemispheric disconnections are efficient and safe procedures. However, both lateral peri-insular hemispherotomy and vertical paramedian hemispherotomy approaches report a failure rate around 20%, which can be explained by residual connections giving rise to persistent seizures. In this study, we present the interhemispheric vertical hemispherotomy (IVH), a technical variation of the vertical paramedian hemispherotomy approach, that aims to increase seizure control avoiding residual connections while exposing the corpus callosum. METHODS: This is a retrospective study of IVH in two centers, with analysis of clinical and MRI data and outcomes. A detailed description of the technique is provided with a video. RESULTS: IVH was performed in 39 children. The mean age at surgery was 7.2 years, and etiologies were as follows: malformations of cortical development (n = 14), Rasmussen's encephalitis (n = 10), stroke (n = 10), post-traumatic (3), and Sturge-Weber Syndrome (2). Hemispheric disconnection was complete on postoperative MRI in 34 cases. There was no mortality, hydrocephalus occurred in one case, and subdural collection occurred in four cases. A second surgery was performed in four cases because of seizure relapse (n = 3) and/or incomplete disconnection on MRI (n = 4). With a mean follow-up of 3.2 years, International League Against Epilepsy class I epilepsy outcome was obtained for 37/39 patients. CONCLUSION: IVH is a safe and effective variation of the vertical approaches for hemispheric disconnection. It allows a good exposure and anatomic control of the corpus callosum, which is a frequent site of incomplete disconnection. IVH may be limited by the thalamic volume and the ventricular size, notably in hemimegalencephaly cases.

Paricalcitol improved cardiac hypertrophy and fibrosis through upregulation of fibroblast growth factor-23 and downregulation of transforming growth factor-beta in a rat model of isoproterenol-induced cardiomyopathy.

Acute cardiomyopathy is a significant global health concern and one of the leading causes of death in developed countries. Prior studies have shown an association between acute cardiomyopathy and low vitamin D levels. Although paricalcitol, a vitamin D receptor (VDR) activator, has demonstrated clinical benefits in patients with advanced kidney disease, its effect on cardiac remodeling in cardiomyopathy is unknown. This study aimed to investigate the relative effects of paricalcitol on cardiomyopathy in rats. Wistar-Kyoto rats were administered vehicle (sham control group) or isoproterenol to induce cardiomyopathy. Rats administered isoproterenol were subsequently treated with paricalcitol (experimental group) or vehicle (isoproterenol group). Picrosirius red and immunofluorescence staining were used to analyze cardiac fibrosis and hypertrophy. Immunohistochemistry staining was used to confirm the molecular mechanisms involved in isoproterenol-induced cardiomyopathy in rats. Injection of paricalcitol could reduce collagen and transforming growth factor-beta 1 (TGF-ß1) levels while activating fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-23 (FGF23) without the help of Klotho, thereby reducing myocardial hypertrophy and fibrosis. As a VDR activator, paricalcitol reduces isoproterenol-induced cardiac fibrosis and hypertrophy by reducing the expression of TGF-ß1 and enhancing the expression of VDR, FGFR1, and FGF23.

Early predictors for maltreatment-related injuries in infancy and long-term mortality: a population-based study.

INTRODUCTION: Incidence, health consequences, and social burden associated with child maltreatment appeared to be borne disproportionately by very young children. We conducted a population-based data linkage study to explore child- and family-level factors that affect receiving different diagnoses of maltreatment injuries and investigate excessive mortality throughout toddlerhood. METHODS: We conducted a retrospective cohort study comprising 2.2 million infants born in 2004-2014 in Taiwan. Incident cases of child maltreatment were defined by hospitalization or emergency department visits for three heterogeneous diagnostic groups of maltreatment-related injuries (i.e., maltreatment syndrome, assaults, and undetermined causes) within 12 months after birth. The generalized linear model and landmark survival analyses were used to evaluate risk factors. RESULTS: An estimated 2.9‰ of infants experienced at least one maltreatment-related injury, with a three-year mortality rate of 1.3%. Low birthweight was associated with increased risk of receiving the diagnosis of three maltreatment injuries, particularly maltreatment syndrome (adjusted Incidence Rate Ratio [aIRR] = 4.08, 95% confidence interval [CI]: 2.93-5.68). Socially advantaged family condition was inversely linked with receiving the diagnosis of maltreatment syndrome and assaults (e.g., high income: aIRR = 0.55 and 0.47), yet positively linked with undetermined cause (aIRR = 2.05, 95% CI: 1.89-2.23). For infants exposed to maltreatment, low birth weight and non-attendance of postnatal care were highly predictive of fatality; low birthweight served as a vital predictor for premature death during toddlerhood (aIRR = 6.17, 95% CI: 2.36-15.4). CONCLUSIONS: Raising awareness of maltreatment-related injuries in infancy and predictors should be a priority for appropriate follow-up assessment and timely intervention.

Intravascular laser irradiation of blood as novel migraine treatment: an observational study.

BACKGROUND: Migraine is one of four major chronic diseases that cause disability. Decreases in regional cerebral blood flow (rCBF) occur during migraine attacks. Laser therapy is extensively employed in treating other vascular diseases; nevertheless, its effectiveness in migraine management remains largely unknown. Therefore, we evaluated the effect of low-level intravascular laser irradiation of blood (ILIB) therapy in patients with migraine. METHODS: We performed an observational case-control study in 24 patients suffering from migraine. Patients were divided into an ILIB treatment group and a traditional rehabilitation group. This study performed clinical assessments and single-photon emission computed tomography (SPECT) prior to and after the treatment and 1 month later. Changes in rCBF-SPECT between groups and between timepoints were compared to clinical outcomes. RESULTS: Nine patients undergoing rehabilitation and fifteen patients undergoing ILIB were studied from baseline to 1 month follow-up. The ILIB group, visual analog scale for pain (P = 0.001), Montreal Cognitive Assessment (P = 0.003), and Athens Insomnia Scale (P < 0.001) symptom scores significantly improved after treatment. SPECT imaging showed a 1.27 ± 0.27 fold increase in rCBF after ILIB treatment, and no significant differences in the rehabilitation group. CONCLUSIONS: Low-level ILIB therapy is associated with better clinical and vascular outcomes, and may be a feasible treatment option for migraine. Although our sample size was small, our data provide a starting point for migraine laser therapy research.

Predictive value of motor-evoked potentials for motor recovery in patients with hemiparesis secondary to acute ischemic stroke.

BACKGROUND: Motor recovery following a stroke is related to the initial stroke severity and corticospinal tract integrity. One of the outcomes representing corticospinal tract integrity is the motor evoked potential (MEP). This study aimed to investigate the predictive value of MEP for motor recovery in patients with acute ischemic stroke. PATIENTS AND METHODS: Patients with hemiparesis secondary to initial acute ischemic stroke were enrolled. MEPs of the upper limb were assessed as preserved (MEP+) or absent (MEP-) response ≤10 days post-stroke. Fugl-Meyer assessment (FMA) was performed at baseline and post-stroke at 30 and 90 days. A modified Rankin scale (mRS) was conducted at 90 days post-stroke. Patients were divided into two groups according to the highest FMA score of MEP- patients. Generalized estimating equations and logistic regression were used for our study analysis. RESULTS: Sixty-one participants were included in this study. The highest FMA score of MEP- patients ≤10 days after stroke was 38. Among patients with an initial FMA score ≤38, FMA scores at 30 and 90 days post-stroke were significantly higher in MEP + patients than in MEP- patients. Proportional recovery at 30 and 90 days post-stroke was significantly higher in MEP + patients than in MEP- patients. MEP + patients had a higher percentage of good functional outcomes than MEP- patients, without statistical difference. Among patients with initial FMA score >38, FMA scores were 60.4 ± 4.8 and 63.9 ± 2.9 and proportional recovery was 65.2 ± 27.0% and 83.7 ± 24.6% at 30 and 90 days post-stroke, respectively. CONCLUSIONS: Among patients with moderate-to-severe ischemic stroke, MEP + patients had better motor recoveries (approximately 70%) than MEP- patients at 90 days post-stroke. MEP + patients had better functional outcomes than MEP- patients.

Key MessagesAmong patients with moderate-to-severe ischemic stroke, those with positive motor-evoked potentials (MEPs) had better motor recovery than those with negative MEPs at 90 days post-stroke.Assessment of motor-evoked potentials is a reliable method for predicting motor recovery in patients with moderate-to-severe ischemic stroke.Corticospinal tract function of patients with acute ischemic stroke was tested with transcranial magnetic stimulation.

SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.

A case series and literature review on 98 pediatric patients of germ cell tumor developing growing teratoma syndrome.

INTRODUCTION: Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited. METHODS: We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS. RESULTS: The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety-five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event-free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5-year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001). CONCLUSION: For patients with high-risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.

Prognostic Factors for Attempted Finger Replantation and Revascularisation after Traumatic Amputation: A 16-Year Retrospective Cohort Study.

Background: The aim of this study was to evaluate the impact of variant factors on finger replantation and revascularisation after traumatic amputation, which also included duty shift and the level of main operator. Methods: To determine the prognostic factors for the survival rate of finger replantation and revascularisation after traumatic finger amputation, we retrospectively reviewed the cases of finger replantation conducted from January 2001 to December 2017. Data collected consisted of the basic information of the patients, trauma-related factors, details of the operation and treatment outcomes. Descriptive statistics and data analysis was performed to assess outcomes. Results: In total, 150 patients with 198 replanted digits were enrolled in this study. The median age of the participants was 42.5 years, and 132 (88%) patients were men. The overall successful replantation rate was 86.4%. Seventy-three (36.9%) digits had Yamano type 1 injury; 110 (55.6%), Yamano type 2 injury and 15 (7.6%), Yamano type 3 injury. In total, 73 (36.9%) digits were completely amputated and 125 (63.1%) were not. Half of the replantation procedures (101, 51.0%) were performed during night shift (16:00-00:00), 69 (34.8%) during day shift (08:00-16:00) and 28 (14.1%) during graveyard shift (00:00-08:00). Multivariate logistic regression demonstrated that the trauma mechanism and type of amputation (complete vs. incomplete) significantly affect the survival rate of replantation. Conclusions: The trauma mechanism and type of amputation (complete vs. incomplete) significantly affect the survival rate of replantation. Other factors including duty shift and the level of operator did not reach statistically significance. Further studies must be conducted to validate the results of the current study. Level of Evidence: Level III (Prognostic).

MRI features of pediatric atypical teratoid rhabdoid tumors and medulloblastomas of the posterior fossa.

BACKGROUND: Atypical teratoid rhabdoid tumor (AT/RT) occurs at a younger age and is associated with a worse prognosis than medulloblastoma; however, these two tumor entities are mostly indistinguishable on neuroimaging. The aim of our study was to differentiate AT/RT and medulloblastoma based on their clinical and MRI features to enhance treatment planning and outcome prediction. METHODS: From 2005-2021, we retrospectively enrolled 16 patients with histopathologically diagnosed AT/RT and 57 patients with medulloblastoma at our institute. We evaluated their clinical data and MRI findings, including lesion signals, intratumoral morphologies, and peritumoral/distal involvement. RESULTS: The age of children with AT/RT was younger than that of children with medulloblastoma (2.8 ± 4.9 [0-17] vs. 6.5 ± 4.0 [0-18], p < 0.001), and the overall survival rate was lower (21.4% vs. 66.0%, p = 0.005). Regarding lesion signals on MRI, AT/RT had a lower ADCmin (cutoff value ≤544.7 × 10-6  mm2 /s, p < 0.001), a lower ADC ratio (cutoff value ≤0.705, p < 0.001), and a higher DWI ratio (cutoff value ≥1.595, p < 0.001) than medulloblastoma. Regarding intratumoral morphology, the "tumor central vein sign" was mostly exclusive to medulloblastoma (24/57, 42.1%; AT/RT 1/16, 6.3%; p = 0.007). Regarding peritumoral invasion on T2WI, AT/RT was more prone to invasion of the brainstem (p < 0.001) and middle cerebellar peduncle (p < 0.001) than medulloblastoma. CONCLUSIONS: MRI findings of a lower ADC value, more peritumoral invasion, and absence of the "tumor central vein sign" may be helpful to differentiate AT/RT from medulloblastoma. These distinct MRI findings together with the younger age of AT/RT patients may explain the worse outcomes in AT/RT patients.

Hypoxia-Induced Kidney Injury in Newborn Rats.

Exposure to hypoxia during the early postnatal period can have adverse effects on vital organs. Neonatal Sprague-Dawley rats housed in a hypoxic chamber were compared to those in a normoxic chamber from postnatal days 0 to 7. Arterial blood was collected to evaluate renal function and hypoxia. Kidney morphology and fibrosis were evaluated using staining methods and immunoblotting. In the kidneys of the hypoxic group, protein expressions of hypoxia-inducible factor-1 were higher than those in the normoxic group. Hypoxic rats had higher levels of hematocrit, serum creatinine, and lactate than normoxic rats. Body weight was reduced, and protein loss of kidney tissue was observed in hypoxic rats compared to normoxic rats. Histologically, hypoxic rats showed glomerular atrophy and tubular injury. Renal fibrosis with collagen fiber deposition was observed in the hypoxic group. The expression of nicotinamide adenine dinucleotide phosphate oxidases was enhanced in the kidneys of hypoxic rats. Proteins involved in apoptosis were upregulated in the kidneys of hypoxic rats. An increase in the expression of pro-inflammatory cytokines was also observed in the kidneys of hypoxic rats. Hypoxic kidney injury in neonatal rats was associated with oxidative stress, inflammation, apoptosis, and fibrosis.

Improved Trends in the Mortality-to-Incidence Ratios for Liver Cancer in Countries with High Development Index and Health Expenditures.

Primary liver cancer is one of the leading causes of death globally. Liver cancer has a unique geographical distribution, as its etiologies include chronic viral infections and aging. We hypothesize that the human development index (HDI), current health expenditure (CHE) per capita, and CHE-to-gross domestic product ratio (CHE/GDP) influence the incidence, mortality, and mortality-to-incidence ratios (MIRs) of liver cancer worldwide. Data were obtained from the Global Cancer Observatory (GLOBOCAN) database and the World Health Organization. MIRs and the changes in MIR over time (δMIR) were used to evaluate the correlation of expenditures on healthcare and the HDI disparities via Spearman's rank correlation coefficient. The crude incidence and mortality were significantly associated with HDI, CHE per capita, and CHE/GDP. Specifically, there were significant associations between δMIR and HDI, as well as between δMIR and CHE per capita. However, there were no significant associations between δMIR and CHE/GDP. Evidently, a favorable liver cancer δMIR was not associated with CHE/GDP, although it had a significant association with HDI and CHE per capita. These results are worthy of the attention of public health systems in correlation to improved outcomes in liver cancer.

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.