Patterns of Failure for Pediatric Glioblastoma Multiforme Following Radiation Therapy

Despite aggressive multimodal therapy for pediatric glioblastoma multiforme (GBM), patient survival remains poor. This retrospective review of patients with GBM aims to evaluate the patterns of failure after radiation therapy (RT). The study included 14 pediatric patients treated with RT at the Children's Hospital of Philadelphia from 2007 to 2015. With a median follow‐up of 16.9 months, 13 (92.9%) developed recurrent disease. Of recurrences, nine (69.2%) were in‐field, three (23.1%) were marginal, and one (7.7%) was distant. The majority of patients treated with adjuvant radiation failed in the region of high‐dose RT, indicating the need for improvements in local therapy.     

Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders

Objective: To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders.

Methods: Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5?mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters.

Results: In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar.

Conclusion: Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.     

Demonstration of In Vitro Host-Guest Complex Formation and Safety of para-Sulfonatocalix[8]arene as a Delivery Vehicle for Two Antibiotic Drugs

The macrocycle para-sulfonatocalix[8]arene, sCX[8], was examined with 2 antibiotic drugs, ciprofloxacin (CIP) and isoniazid. The drugs were shown to form complexes with sCX[8] using proton nuclear magnetic resonance, thermogravimetric analysis, fluorescence spectroscopy, and molecular modeling. Both drugs form 1:1 hydrated (H₂O: 13%-14% w/w) host-guest complexes, with sCX[8] binding around the pyridine ring of isoniazid, and around the piperazine and cyclopropane rings of CIP. From proton nuclear magnetic resonance, the binding constant of isoniazid to sCX[8] was 6.8 (±0.3) × 10³ M^?1. Addition of 2 equivalents of sCX[8] to CIP resulted in a 58% decrease in fluorescence, and time-resolved fluorescence anisotropy of CIP doubles with sCX[8]. Each drug binds into the cavity of the macrocycle, with binding stabilized via combinations of hydrogen bonding, electrostatic interactions, π-π stacking, and hydrophobic effects. The safety of sCX[8] was examined in vitro with human embryonic kidney 293 cells. The IC₅₀ of sCX[8] was 559 μM, which is a minimum of 5-fold higher than the concentration that would be used in the clinic. The in vitro effect of sCX[8] on the action of CIP was examined on a panel of bacterial lines. The results showed that sCX[8] has no inherent antibiotic activity and had no negative effect on the action of CIP.     

The prosthodontic restoration of a self-inflicted gunshot maxillofacial defect: a short-term follow-up case report

A self-inflicted gunshot maxillofacial defect was restored with dental implants and various attachments. Following mandibular surgical reconstruction, a fixed full-arch implant-supported prosthesis was fabricated. The maxillary defect was restored with an obturator retained with bar-clip and ball attachments. Crowns with an unfavorable crown-to-root ratio were used to rectify a compromised unilateral interocclusal space. Functional rehabilitation was achieved without any pathologic sequelae and maintained over a 1-year observation period. Provision of a fixed implant-retained mandibular prosthesis opposing a specific design for a maxillary obturator provided short-term and optimistic prognosis in the management of a serious traumatic injury.     

Eviszeration von Darm nach Stichverletzung des Abdomens

Study aim

The aim of the study was an estimation of the incidence and clinical aspects of emergency room (ER) parameters of penetrating abdominal injury patients with bowel evisceration.

Study design and methods

The study involved a retrospective cohort analysis of ER data from the Chris Hani Baragwanath Academic Hospitals, Soweto, Johannesburg, South Africa between September 2000 to May 2005.

Results

Out of 9,010 ER patients, 4,390 suffered penetrating injuries with 8 out of 71 eviscerations due to a single gunshot wound, 60 out of 71 eviscerations due to single stab wounds and 3 further patients suffered multiple injuries. The ER mortality was 1 out of 71(1.6 %) with an average ER mortality of 4.2 %. The only death seen was a single abdominal gunshot wound with vascular injury. The causative mortality due to abdominal stab wounds with evisceration of the bowels was therefore zero. The heart rate in patients with abdominal stab wounds with and without bowel evisceration showed no significant difference, thus mesentery tearing or vagal overstimulation could not be seen, neither with bradycardia nor hypotension.

Conclusion

Evisceration itself is not a cause for increased mortality or cardiovascular instability seen in the ER. There is ample time for diagnostic procedures before laparotomy is performed.     

Metabolic clearance rates of catechol estrogens in rats

MCRs of the catechol estrogens 4-hydroxyestradiol (4-OHE2) and 2-hydroxyestradiol (2-OHE2) and of the parent estrogen 17 beta-estradiol (E2) were determined in rats. Long term ovariectomized Wistar rats were infused with the steroids at a constant rate for 3 days via a catheter placed in the abdominal aorta. Blood samples were drawn discontinually by retroorbital puncture, and the serum concentrations of E2, 4-OHE2, and 2-OHE2 were measured by RIA. Steady state was reached within 24 h of infusion. Mean serum MCRs were calculated to be 740 +/- 117 ml/h for E2, 2700 +/- 1000 ml/h for 4-OHE2, and 8300 +/- 1700 ml/h for 2-OHE2. Thus, the MCRs of the catechol estrogens were definitely higher than the MCR of E2 resulting in an apparent ratio of 1:4:11 (E2:4-OHE2:2-OHE2).     

In vitro leishmanicidal activity of monomeric and dimeric naphthoquinones

A series of monomeric and dimeric naphthoquinones with potential for treatment of Leishmania infections was identified in vitro using both a direct cytotoxicity assay against extracellular promastigotes of Leishmania donovani, L. infantum, L. enriettii, and L. major and a test against intracellular amastigote L. donovani residing within murine macrophages. Several naphthoquinones proved to be active at concentrations in the microgram range (EC(50) 0.9-17.0 microg/ml). When tested against a panel of human cancer cell lines (KB, SKMel, A549, MDA) and murine bone marrow culture-derived macrophages (BMMPhi) as mammalian host cell controls, compounds with anti-Leishmania-activity showed moderate (EC(50)>25 microg/ml) to pronounced (EC(50)<10 microg/ml) toxic effects.     

Frontal theta and posterior alpha in resting EEG: A critical examination of convergent and discriminant validity

Prior research has identified two resting EEG biomarkers with potential for predicting functional outcomes in depression: theta current density in frontal brain regions (especially rostral anterior cingulate cortex) and alpha power over posterior scalp regions. As little is known about the discriminant and convergent validity of these putative biomarkers, a thorough evaluation of these psychometric properties was conducted toward the goal of improving clinical utility of these markers. Resting 71-channel EEG recorded from 35 healthy adults at two sessions (1-week retest) were used to systematically compare different quantification techniques for theta and alpha sources at scalp (surface Laplacian or current source density [CSD]) and brain (distributed inverse; exact low resolution electromagnetic tomography [eLORETA]) level. Signal quality was evaluated with signal-to-noise ratio, participant-level spectra, and frequency PCA covariance decomposition. Convergent and discriminant validity were assessed within a multitrait-multimethod framework. Posterior alpha was reliably identified as two spectral components, each with unique spatial patterns and condition effects (eyes open/closed), high signal quality, and good convergent and discriminant validity. In contrast, frontal theta was characterized by one low-variance component, low signal quality, lack of a distinct spectral peak, and mixed validity. Correlations between candidate biomarkers suggest that posterior alpha components constitute reliable, convergent, and discriminant biometrics in healthy adults. Component-based identification of spectral activity (CSD/eLORETA-fPCA) was superior to fixed, a priori frequency bands. Improved quantification and conceptualization of frontal theta is necessary to determine clinical utility.