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Abstract: Epidermoid splenic cyst is a rare benign tumour in children, accounting for 10% of all cystic lesions of the spleen and is the most common diagnosis of non-parasitic splenic cysts. Its discovery could be incidental or happen after an imaging workup for a mass or abdominal pain. Since total splenectomy exposes a patient to the occurrence of overwhelming post-splenectomy infection, laparoscopic partial splenectomy has been increasingly popular over the past two decades because it preserves the immune function of the spleen. This technique should only be performed by a well-trained team because of the high risk of bleeding. The authors report the cases of three patients who underwent laparoscopic partial splenectomy: a 7-year-old girl with no relevant history with a 4.5-cm epidermoid cyst involving the lower pole of the spleen, a 13-year-old boy, type 1 diabetic on insulin therapy, with a 7-cm epidermoid cyst of the upper pole of the spleen and a 14-year-old girl, with no previous history, with a 6-cm upper pole epidermoid splenic cyst. Operating times were 2 h 30 min, 3 h and 4 h 30 min, respectively. The intraoperative blood loss was 100 mL, 350 mL and 300 mL, respectively. The length of hospital stay was 6 days for each patient. No blood transfusion was performed perioperatively. With a mean follow-up duration of 21 months (32 months, 21 months and 10 months, respectively), no complication or recurrence occurred., (Copyright © 2024 Copyright: © 2024 African Journal of Paediatric Surgery.)

Background: In surgery, simulated-based training improves the knowledge and interpersonal skills needed for surgeons to improve their performance and meet the "never the first time on a patient" imperative. The objective is to evaluate the effects of a 2017 reform on surgeon's accessibility to simulation-based training, five years after the implementation of the program, and to gauge surgeon satisfaction., Methods: A 27-item national online survey was sent to all surgical residents and fellows in the 13 surgical specialties., Results: Among 523 responses, 405 (77.4%) were residents and 118 (22.6%) were surgical fellows. Two hundred forty-seven (47.2%) of surgical residents and fellows stated they did not have a simulation structure or simulation program in the town of their university hospital center. Two hundred thirty-five (44.9%) reported having simulation training programs and 41 (7.8%) reported having easy and free access to their simulation structure. Regarding simulation-based training, 44.6% of surgical residents and fellows had never received training in technical skills on simulators, 82.2% had never received training in teamwork or interprofessional skills and 76.1% had never received training in behavioral or relational skills. There was a significant difference between the degree of satisfaction of residents at the beginning and at the end of the study (P=0.02)., Conclusion: Simulation is a well-established educational tool, but there are still strong inequalities between universities. Despite the national deployment of simulation-based teaching programs and institutional efforts, surgical simulation is insufficiently developed in France, and learner satisfaction is poor., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: To evaluate the feasibility and describe the relevant differences between robotic cholecystectomy (RC) and laparoscopic cholecystectomy in a canine model., Sample: Canine cadavers (n = 4) weighing between 30 and 42 kg., Methods: Dogs were positioned in dorsal recumbency. A surgical robot was used to perform the RC and was placed at the cranial aspect of the surgical table. One 12-mm and 3 8-mm robotic ports and 1 5-mm laparoscopic port were placed as needed to perform the RC. The specific steps of the procedure were described and timed. Perceived differences between psychomotor skills between robotics and laparoscopy were noted., Results: RC was successful in all dogs, but minor intraoperative complications did occur during the manipulation of the gallbladder in 1 dog. The median length of time for ports to be appropriately docked was 19.5 minutes, and the median procedure time was 119.5 minutes. Psychomotor skills specific to robotics can be learned during this procedure., Clinical Relevance: Robotic cholecystectomy is feasible. RC allowed for experience with the different psychomotor skills utilized with robotic instrumentation and may be an appropriate training procedure for veterinary surgeons wishing to gain basic experience with robotic instrumentation.

Lysosomotropic agent chloroquine was shown to sensitize non-stem glioblastoma cells to radiation in vitro with p53-dependent apoptosis implicated as one of the underlying mechanisms. The in vivo outcomes of chloroquine or its effects on glioblastoma stem cells have not been previously addressed. This study undertakes a combinatorial approach encompassing in vitro, in vivo and in silico investigations to address the relationship between chloroquine-mediated radiosensitization and p53 status in glioblastoma stem cells. Our findings reveal that chloroquine elicits antagonistic impacts on signaling pathways involved in the regulation of cell fate via both transcription-dependent and transcription-independent mechanisms. Evidence is provided that transcriptional impacts of chloroquine are primarily determined by p53 with chloroquine-mediated activation of pro-survival mevalonate and p21-DREAM pathways being the dominant response in the background of wild type p53. Non-transcriptional effects of chloroquine are conserved and converge on key cell fate regulators ATM, HIPK2 and AKT in glioblastoma stem cells irrespective of their p53 status. Our findings indicate that pro-survival responses elicited by chloroquine predominate in the context of wild type p53 and are diminished in cells with transcriptionally impaired p53. We conclude that p53 is an important determinant of the balance between pro-survival and pro-death impacts of chloroquine and propose that p53 functional status should be taken into consideration when evaluating the efficacy of glioblastoma radiosensitization by chloroquine.

Introduction: Gastro-esophageal reflux disease (GERD) is the most frequent long-term morbidity of congenital diaphragmatic hernia (CDH) survivors. Performing a preventive fundoplication during CDH repair remains controversial. This study aimed to: (1) Analyze the variability in practices regarding preventive fundoplication; (2) Identify predictive factors for fundoplication. (3) Evaluate the impact of preventive fundoplication on gastro-intestinal outcomes in children with a CDH patch repair; METHODS: This prospective multi-institutional cohort study (French CDH Registry) included CDH neonates born in France between January 1st, 2010-December 31st, 2018. Patch CDH was defined as need for synthetic patch or muscle flap repair. Main outcome measures included need for curative fundoplication, tube feed supplementation, failure to thrive, and oral aversion., Results: Of 762 CDH neonates included, 81 underwent fundoplication (10.6%), either preventive or curative. Median follow-up was 3.0 years (IQR: 1.0-5.0). (1) Preventive fundoplication is considered in only 31% of centers. The rates of both curative fundoplication (9% vs 3%, p = 0.01) and overall fundoplication (20% vs 3%, p < 0.0001) are higher in centers that perform preventive fundoplication compared to those that do not. (2) Predictive factors for preventive fundoplication were: prenatal diagnosis (p = 0.006), intra-thoracic liver (p = 0.005), fetal tracheal occlusion (p = 0.002), CDH-grade C-D (p < 0.0001), patch repair (p < 0.0001). After CDH repair, 8% (n = 51) required curative fundoplication (median age: 101 days), for which a patch repair was the only independent predictive factors identified upon multivariate analysis. (3) In neonates with patch CDH, preventive fundoplication did not decrease the need for curative fundoplication (15% vs 11%, p = 0.53), and was associated with higher rates of failure to thrive (discharge: 81% vs 51%, p = 0.03; 6-months: 81% vs 45%, p = 0.008), tube feeds (6-months: 50% vs 21%, p = 0.02; 2-years: 65% vs 26%, p = 0.004), and oral aversion (6-months: 67% vs 37%, p = 0.02; 1-year: 71% vs 40%, p = 0.03)., Conclusions: Children undergoing a CDH patch repair are at high risk of requiring a curative fundoplication. However, preventive fundoplication during a patch repair does not decrease the need for curative fundoplication and is associated with worse gastro-intestinal outcomes in children., Level of Evidence: II - Prospective Study., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To assess the outcomes of continent urinary diversion according to the Mitrofanoff principle by robot-assisted laparoscopic surgery in terms of continence, catheterization and repeat surgery., Methods: All adult patients who underwent procedures for continent urinary diversion via a robot-assisted laparoscopic route between October 2014 and November 2018 were enrolled retrospectively. Abdominal continence and clean intermittent catheterization ability were noted, as well as patient characteristics, details of the technique, intra- and perioperative parameters, and complications., Results: Ten patients were included. Bladder-sphincter disorders were due to neurological causes in nine patients, and one patient had idiopathic bladder sphincter dyssynergia. A continent catheterizable channel was created using the appendix in six cases and the ileum in four cases. The median operative duration was 245 min (IQR 228-370). Two patients had a Clavien 3 complication requiring laparoscopy to separately drain a haematoma and a pelvic abscess. The median follow-up was 21 months (IQR 17-27). Abdominal continence without further intervention was obtained in 6/10 patients (60%). Two patients needed an open revision of the continent urinary diversion, one required injection of Deflux ® and one an intradetrusorian injection of botulinum toxin type A (Botox ® ). Further surgery was needed for two patients to improve urethral continence. At the end of follow-up, all patients were continent and clean intermittent catheterization was possible., Conclusion: Continent urinary diversion performed according to the Mitrofanoff principle is possible via a robot-assisted laparoscopic route and yields good outcomes on abdominal continence in the short term in patients with clean intermittent catheterization ability.

Blunt testicular trauma with rupture of albuginea is one of the rarest emergencies in children. Medical history and Testicular Doppler Ultrasound lead to diagnosis. Appropriate management is necessary to preserve the testis. Follow-up to adulthood is recommended to assess the impact on fertility., (© 2021 Published by Elsevier Ltd.)

Previously we showed that human monocytes isolated from peripheral blood display downregulation of several DNA repair proteins, including XRCC1, ligase III, PARP-1 and DNA-PK CS, resulting in a deficiency of DNA repair, while in macrophages derived from monocytes the repair protein expression and DNA repair is restored. To see whether this is a specific phenomenon of human monocytes and macrophages, we assessed the expression of these repair genes in mice. We also addressed the question at which differentiation step in bone marrow cells downregulation of DNA repair gene expression occurs. The study revealed that mouse monocytes, similar to human, lack the expression of XRCC1, ligase III, PARP-1 and DNA-PK CS . If mice were treated with total body irradiation, they showed significant apoptosis in bone marrow monocytes, but not in peritoneal macrophages. This was also observed after treatment with the methylating anticancer drug temozolomide, resulting in high death rate of monocytes, but not macrophages. Monocytes arise from hematopoietic stem cells. Even the early stem cell fraction (LT-HSC) expressed detectable amounts of XRCC1, which was transiently upregulated, achieving the highest expression level in CMP (common myeloid progenitor) and, during the subsequent differentiation process, downregulated up to a non-detectable level in monocytes. The immediate monocyte precursor GMP also expressed ligase III, PARP-1 and DNA-PK CS . All these repair genes lacking in monocytes were upregulated again in macrophages. The sensitivity of monocytes, macrophages and precursor cells roughly correlated with their XRCC1 expression level. Monocytes, but not macrophages, also displayed strong γH2AX focal staining, indicating the presence of non-repaired DNA double-strand breaks following total body irradiation. Overall, the data revealed that murine monocytes exhibit the same DNA repair-impaired phenotype and high sensitivity compared to macrophages as observed in human. Therefore, the repair deficiency previously described for human monocytes appears to be a general property of this cell type., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The new tools for transmission of knowledge and skills (simulation, surgery broadcast, virtual reality, augmented reality…) offer novel opportunities for training through mentoring. The peer network is widened; the dissemination of knowledge is accelerated. The new ways of teaching bring benefit to each aspect of the surgical profession: clinical reasoning, performance of technical procedures, stress management, communication and management of severe or exceptional adverse events. Previously, confined to surgical teams, mentoring has been extended to simulation centers, which are becoming virtual hospitals, and it has been prolonged on the Internet via social networks. In the sphere of digital mentoring, objectives are henceforth more structured, skills assessment is more standardized, phases of apprenticeship are redefined, and individualized training contracts are formalized., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The DNA-methylating drug temozolomide, which induces cell death through apoptosis, is used for the treatment of malignant glioma. Here, we investigate the mechanisms underlying the ability of temozolomide to induce senescence in glioblastoma cells. Temozolomide-induced senescence was triggered by the specific DNA lesion O 6 -methylguanine (O 6 MeG) and characterized by arrest of cells in the G 2 -M phase. Inhibitor experiments revealed that temozolomide-induced senescence was initiated by damage recognition through the MRN complex, activation of the ATR/CHK1 axis of the DNA damage response pathway, and mediated by degradation of CDC25c. Temozolomide-induced senescence required functional p53 and was dependent on sustained p21 induction. p53-deficient cells, not expressing p21, failed to induce senescence, but were still able to induce a G 2 -M arrest. p14 and p16, targets of p53, were silenced in our cell system and did not seem to play a role in temozolomide-induced senescence. In addition to p21, the NF-κB pathway was required for senescence, which was accompanied by induction of the senescence-associated secretory phenotype. Upon temozolomide exposure, we found a strong repression of the mismatch repair proteins MSH2, MSH6, and EXO1 as well as the homologous recombination protein RAD51, which was downregulated by disruption of the E2F1/DP1 complex. Repression of these repair factors was not observed in G 2 -M arrested p53-deficient cells and, therefore, it seems to represent a specific trait of temozolomide-induced senescence. SIGNIFICANCE: These findings reveal a mechanism by which the anticancer drug temozolomide induces senescence and downregulation of DNA repair pathways in glioma cells., (©2018 American Association for Cancer Research.)

Introduction: Congenital Lower Urinary Tract Obstructions (LUTO) is a heterogeneous group of diseases in which urine elimination is obstructed at the level of bladder neck or urethra. The aim of the study is to evaluate the long-term renal outcome of patients suffering of congenital LUTO., Patients and Method: We retrospectively reviewed patients with congenital LUTO. All patients had at least 1 year follow-up. Data on surgery, renal imaging and Schwartz estimate creatinine clearance were collected. Incidence of Chronic Renal Disease (CRD) is presented with Kaplan-Meier method., Results: 40 patients were included, 23 patients with Posterior Urethral Valve (PUVs) and 17 patients with other aetiologies: anterior urethral valve (2), urethral atresia (2), urethral stenosis (2), cloacal malformations (2), obstructive ureterocele (1), bladder trigone malformation (1) and neonatal bladder-sphincter dysfunction without neurological abnormalities (7). Incidence of CRD at age 10 years was 37% in congenital LUTO, 42% in PUVs and 30% in other aetiologies, and was significantly higher in PUVs (P=0.032). Renal prognosis was significantly worsened by discover of retentional bladder wall changes in initial cystoscopy, and by loss of parenchymal differentiation or cortical microcysts in first ultrasonography. The use of urinary diversion was significantly higher in LUTO of other aetiologies., Conclusion: A high incidence of CRD is observed in patients with congenital LUTO, significantly higher in patients with PUV. LUTO of other aetiologies require step by step surgical management and higher use of urinary diversion. Precise initial evaluation in cystoscopy and ultrasonography is required and participate to evaluate future renal outcome., Level of Incidence: 4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Importance: Though theoretically sound, studies have failed to demonstrate the benefit of routine repositioning of at-risk patients for the prevention of hospital acquired pressure injuries., Objective: To assess the clinical effectiveness of a wearable patient sensor to improve care delivery and patient outcomes by increasing the total time with turning compliance and preventing pressure injuries in acutely ill patients., Design: Pragmatic, investigator initiated, open label, single site, randomized clinical trial., Setting: Two Intensive Care Units in a large Academic Medical Center in California., Participants: Consecutive adult patients admitted to one of two Intensive Care Units between September 2015 to January 2016 were included (n = 1564). Of the eligible patients, 1312 underwent randomization., Intervention: Patients received either turning care relying on traditional turn reminders and standard practices (control group, n = 653), or optimal turning practices, influenced by real-time data derived from a wearable patient sensor (treatment group, n = 659)., Main Outcome(s) and Measure(s): The primary and secondary outcomes of interest were occurrence of hospital acquired pressure injury and turning compliance. Sensitivity analysis was performed to compare intention-to-treat and per-protocol effects., Results: The mean age was 60 years (SD, 17 years); 55% were male. We analyzed 103,000 h of monitoring data. Overall the intervention group had significantly fewer Hospital Acquired Pressure Injuries during Intensive Care Unit admission than the control group (5 patients [0.7%] vs. 15 patients [2.3%] (OR = 0.33, 95%CI [0.12, 0.90], p = 0.031). The total time with turning compliance was significantly different in the intervention group vs. control group (67% vs 54%; difference 0.11, 95%CI [0.08, 0.13], p < 0.001). Turning magnitude (21°, p = 0.923) and adequate depressurization time (39%, p = 0.145) were not statistically different between groups., Conclusions and Relevance: Among acutely ill adult patients requiring Intensive Care Unit admission, the provision of optimal turning was greater with a wearable patient sensor, increasing the total time with turning compliance and demonstrated a statistically significant protective effect against the development of hospital acquired pressure injuries. These are the first quantitative data on turn quality in the Intensive Care Unit and highlight the need to reinforce optimal turning practices. Additional clinical trials leveraging technologies like wearable sensors are needed to establish the appropriate frequency and dosing of individualized turning protocols to prevent pressure injuries in at-risk hospitalized patients., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the status of congenital diaphragmatic hernia (CDH) management in France and to assess predictors of adverse outcomes., Study Design: We reviewed the first-year outcome of all cases of CDH reported to the French National Register in 2011., Results: A total of 158 cases were included. Of these, 83% (131) were prenatally diagnosed, with a mortality rate of 39% (44 of 112) for live born infants with a known outcome at hospital discharge. Mortality increased to 47% (60 of 128) including those with termination of pregnancy and fetal loss. This contrasts with the 7% (2 of 27) mortality rate of the patients diagnosed postnatally (P = .002). Mortality worsened with 1 prenatal marker of CDH severity (OR 3.38 [1.30-8.83] P = .013) and worsened further with 2 markers (OR 20.64 [5.29-80.62] P < .001). Classic postnatal risk factors of mortality such as side of hernia (nonleft P = .001), prematurity (P < .001), low birth weight (P = .002), and size of the defect (P < .001) were confirmed. Of the 141 live births (114 prenatal and 27 postnatal diagnosis) with known outcomes, 93 (67%) survived to hospital discharge, 68 (60%) with a prenatal diagnosis and 25 (93%) with a postnatal diagnosis. The median time to hospital discharge was 34 days (IQR, 19.25-62). Of these survivors, 71 (76%) were followed up for 1 year., Conclusions: Despite advances in management of CDH, mortality was high and associated with prenatal risk factors. Postnatally, severe persistent pulmonary hypertension was difficult to predict and presented persistent challenges in management., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Infantile hepatic hemangioma (IHH) and mesenchymal hamartoma (MH) form the first and second most common benign hepatic tumors in children. In this case report, we present a newborn child in whom a growing hepatic mass was discovered at the age of 7 days. She suffered also from anemia, respiratory and renal failure. No signs of heart disease or cutaneous lesions were detected. Alpha-fetoprotein was elevated for her age (3562.2 ng/ml). Imaging studies showed multifocal large cystic lesions associated with heterogeneous small solid lesions with arterial enhancement of the liver. Non-anatomical liver resection was performed initially and synchronous MH and IHH GLUT-1 positive were discovered in the pathological analysis. Segmental IV hepatic resection and later on selective cysts excision were done for persistent hepatic lesion despite medical treatment. After 14 months of beta-blockers treatment, clinical follow-up shows a healthy child with no residual cystic lesions.

Integrins have been suggested as possible targets in anticancer therapy. Here we show that knockdown of integrins αVβ3, αVβ5, α3β1 and α4β1 and pharmacological inhibition using a cyclo-RGD integrin αVβ3/αVβ5 antagonist sensitized multiple high-grade glioma cell lines to temozolomide (TMZ)-induced cytotoxicity. The greatest effect was observed in LN229 cells upon integrin β3 silencing, which led to inhibition of the FAK/Src/Akt/NFκB signaling pathway and increased formation of γH2AX foci. The integrin β3 knockdown led to the proteasomal degradation of Rad51, reduction of Rad51 foci and reduced repair of TMZ-induced DNA double-strand breaks by impairing homologous recombination efficiency. The down-regulation of β3 in Rad51 knockdown (LN229-Rad51kd) cells neither further sensitized them to TMZ nor increased the number of γH2AX foci, confirming causality between β3 silencing and Rad51 reduction. RIP1 was found cleaved and IκBα significantly less degraded in β3-silenced/TMZ-exposed cells, indicating inactivation of NFκB signaling. The anti-apoptotic proteins Bcl-xL, survivin and XIAP were proteasomally degraded and caspase-3/-2 cleaved. Increased H2AX phosphorylation, caspase-3 cleavage, reduced Rad51 and RIP1 expression, as well as sustained IκBα expression were also observed in mouse glioma xenografts treated with the cyclo-RGD inhibitor and TMZ, confirming the molecular mechanism in vivo. Our data indicates that β3 silencing in glioma cells represents a promising strategy to sensitize high-grade gliomas to TMZ therapy.

Malignant gliomas exhibit a high level of intrinsic and acquired drug resistance and have a dismal prognosis. First- and second-line therapeutics for glioblastomas are alkylating agents, including the chloroethylating nitrosoureas (CNU) lomustine, nimustine, fotemustine, and carmustine. These agents target the tumor DNA, forming O 6 -chloroethylguanine adducts and secondary DNA interstrand cross-links (ICL). These cross-links are supposed to be converted into DNA double-strand breaks, which trigger cell death pathways. Here, we show that lomustine (CCNU) with moderately toxic doses induces ICLs in glioblastoma cells, inhibits DNA replication fork movement, and provokes the formation of DSBs and chromosomal aberrations. Since homologous recombination (HR) is involved in the repair of DSBs formed in response to CNUs, we elucidated whether pharmacologic inhibitors of HR might have impact on these endpoints and enhance the killing effect. We show that the Rad51 inhibitors RI-1 and B02 greatly ameliorate DSBs, chromosomal changes, and the level of apoptosis and necrosis. We also show that an inhibitor of MRE11, mirin, which blocks the formation of the MRN complex and thus the recognition of DSBs, has a sensitizing effect on these endpoints as well. In a glioma xenograft model, the Rad51 inhibitor RI-1 clearly enhanced the effect of CCNU on tumor growth. The data suggest that pharmacologic inhibition of HR, for example by RI-1, is a reasonable strategy for enhancing the anticancer effect of CNUs. Mol Cancer Ther; 15(11); 2665-78. ©2016 AACR., (©2016 American Association for Cancer Research.)

Glioblastoma multiforme (GBM), a malignant brain tumor with a dismal prognosis, shows a high level of chemo- and radioresistance and, therefore, attempts to sensitize glioma cells are highly desired. Here, we addressed the question of whether artesunate (ART), a drug currently used in the treatment of malaria, enhances the killing response of glioblastoma cells to temozolomide (TMZ), which is the first-line therapeutic for GBM. We measured apoptosis, necrosis, autophagy and senescence, and the extent of DNA damage in glioblastoma cells. Further, we determined the tumor growth in nude mice. We show that ART enhances the killing effect of TMZ in glioblastoma cell lines and in glioblastoma stem-like cells. The DNA double-strand break level induced by TMZ was not clearly enhanced in the combined treatment regime. Also, we did not observe an attenuation of TMZ-induced autophagy, which is considered a survival mechanism. However, we observed a significant effect of ART on homologous recombination (HR) with downregulation of RAD51 protein expression and HR activity. Further, we found that ART is able to inhibit senescence induced by TMZ. Since HR and senescence are pro-survival mechanisms, its inhibition by ART appears to be a key node in enhancing the TMZ-induced killing response. Enhancement of the antitumor effect of TMZ by co-administration of ART was also observed in a mouse tumor model. In conclusion, the amelioration of TMZ-induced cell death upon ART co-treatment provides a rational basis for a combination regime of TMZ and ART in glioblastoma therapy.

The outcome of cancer therapy strongly depends on the complex network of cell signaling pathways, including transcription factor activation following drug exposure. Here we assessed whether and how the MAP kinase (MAPK) cascade and its downstream target, the transcription factor AP-1, influence the sensitivity of malignant glioma cells to the anticancer drugs temozolomide (TMZ) and nimustine (ACNU). Both drugs induce apoptosis in glioma cells at late times following treatment. Activation of the MAPK cascade precedes apoptosis, as shown by phosphorylation of Jun kinase (JNK) and c-Jun, a main component of AP-1. Pharmacological inhibition and siRNA mediated knockdown of JNK and c-Jun reduced the level of apoptosis in LN-229 glioma cells treated with TMZ or ACNU. Analyzing the underlying molecular mechanism, we identified the pro-apoptotic gene BIM as a critical target of AP-1, which is upregulated following TMZ and ACNU. Importantly, shRNA mediated downregulation of BIM in the malignant glioma cell lines LN-229 and U87MG led to an attenuated cleavage of caspase-9 and, consequently, reduced the level of apoptosis following TMZ and ACNU treatment. Overall, we identified JNK/c-Jun activation and BIM induction as a late pro-apoptotic response of glioma cells treated with alkylating anticancer drugs.

Introduction: The development of reconstructive surgery of the lower limbs aimed at multilevel correction demands a precise knowledge of the physiological variations in general radiological parameters of the lower limbs in children of various age groups. It is crucial in systemic skeletal diseases, when deformities affect limbs and the surgeon does not have an intact limb as a reference. The aim of this retrospective study was to establish the normal radiological values of lower limb parameters used in the surgical correction of deformities in children of various age groups., Material and Methods: Teleradiographs of the lower limbs taken in children with unilateral congenital or posttraumatic deformity were retrospectively reviewed. Weight-bearing full-length anteroposterior radiographs of the entire lower extremities were taken in a standing position. The study involved 215 extremities of 208 children (93 girls and 115 boys); the ages ranged from 2 years 1 month to 15 years 11 months old. Key variables included the anatomic medial proximal femoral angle (aMPFA), anatomic lateral distal femoral angle (aLDFA), anatomic medial proximal tibial angle (aMPTA), anatomic lateral distal tibial angle (aLDTA), mechanical axis deviation (MAD), the angle formed by the femoral anatomical axis and the mechanical axis of the lower limb., Results: The means and dynamics of variations, standard deviations (SD) and 95% confidence intervals of each parameter were calculated for each age and gender group. Simple regression analysis was performed to determine the relationship between the patient's age and the magnitude of aMPFA, aLDFA, aMPTA and aLDTA. Simple regression analysis showed a significant inverse correlation between patient age and the magnitude of aMPFA: the correlation coefficient was -0.77. A statistically significant inverse correlation between the MAD and the angle between the anatomic femoral axis and mechanical limb axis was found: the correlation coefficient was -0.53., Conclusion: In general, the received values were concordant to results of other studies. It concerned the MAD, aLDFA, aMPTA and angle between the mechanical limb axis and anatomic femoral axis. This is the first chronological evaluation of aMPFA and aLDTA from a relavively large series of patients. These normative data should be taken into consideration when evaluating lower limb alignment in children or applied in practice for planning and evaluation of the quality of surgical correction of complex deformities.