Comparing the oxidative functions of neutrophil myeloperoxidase and cytochrome P450 enzymes in drug metabolism.

Drug metabolism is an essential process that chemically alters xenobiotic substrates to activate or terminate drug activity. Myeloperoxidase (MPO) is a neutrophil-derived haem-containing enzyme that is involved in killing invading pathogens, although consequentially, this same oxidative activity can produce metabolites that damage host tissue and play a role in various human pathologies. Cytochrome P450s (CYPs) are a superfamily of haem-containing enzymes that are significantly involved in the metabolism of drugs by functioning as monooxygenases and can be induced or inhibited, resulting in significant drug-drug interactions that lead to unanticipated adverse drug reactions. In this review, the functions of drug metabolism of MPO and CYPs are explored, along with their involvement and association for common enzymatic pathways by certain xenobiotics. MPO and CYPs metabolize numerous xenobiotics, although few reported studies have made a direct comparison between both enzymes. Additionally, we employed molecular docking to compare the active site and haem prosthetic group of MPO and CYPs, supporting their similar catalytic activities. Furthermore, we performed LCMS analysis and observed a shared hydroxylated mefenamic acid metabolite produced in both enzymatic systems. A proper understanding of the enzymology and mechanisms of action of MPO and CYPs is of significant importance when enhancing the beneficial functions of drugs in health and diminishing their damaging effects on diseases. Therefore, awareness of drugs and xenobiotic substrates involved in MPO and CYPs metabolism pathways will add to the knowledge base to foresee and prevent potential drug interactions and adverse events.

Precision Doppler shift measurements with a frequency comb calibrated laser heterodyne radiometer.

We report precision atmospheric spectroscopy of CO2 using a laser heterodyne radiometer (LHR) calibrated with an optical frequency comb. Using the comb calibrated LHR, we record spectra of atmospheric CO2 near 1572.33 nm with a spectral resolution of 200 MHz, using sunlight as a light source. The measured CO2 spectra exhibit frequency shifts by approximately 11 MHz over the course of the 5-h measurement, and we show that these shifts are caused by Doppler effects due to wind along the spectrometer line of sight. The measured frequency shifts are in excellent agreement with an atmospheric model, and we show that our measurements track the wind-induced Doppler shifts with a relative frequency precision of 2 MHz (3 m·s-1) for a single 10 s measurement, improving to 100 kHz (15 cm·s-1) after averaging (equivalent to a fractional precision of a few parts in 1010). These results demonstrate that frequency comb calibrated LHR enables precision velocimetry that can be of use in applications ranging from climate science to astronomy.

Investigation of the association between the interval from internal teat sealant administration to calving and early lactation clinical mastitis in New Zealand dairy heifers.

AIMS: To examine the association between the interval from internal teat sealant (ITS) administration to calving and the incidence of farmer-recorded clinical mastitis in the first 30 days of lactation in pasture-based dairy heifers. METHODS: Heifers that were administered an ITS by a single veterinary business in the South Island of New Zealand over the winter of 2014 were enrolled in a cross-sectional observational study. ITS was administered to all heifers on each participating farm on a single calendar day. The dates of calving and farmer-diagnosed clinical mastitis were recorded by farm staff. The interval from ITS administration to calving was categorised into four approximately evenly sized groups: <35, 35-48, 49-69 and >69 days. The quartile of the farm's calving period in which each heifer calved was also investigated as a potential confounding variable. A hierarchical logistic regression model was constructed to determine the association between the interval from ITS administration to calving with the odds of clinical mastitis in the first 30 days of lactation. RESULTS: Analysis was performed on 7,126 eligible heifers from 31 farms, with ITS administered between 9 May and 11 July 2014. The mean interval from ITS administration to calving was 52.9 (SD 24.4, min 1, max 137) days. Clinical mastitis was diagnosed in 420/7,126 (5.9 (95% CI=5.4-6.5)%) heifers between calving and day 30 of lactation. In the final multivariable model, which included calving period quartile, interval from ITS administration to calving was not associated with the odds of clinical mastitis (p=0.516). Compared to an interval from ITS administration to calving of <35 days, the adjusted OR of clinical mastitis for intervals of 35-48, 49-69 and >69 days were 0.83 (95% CI=0.59-1.17), 0.71 (95% CI=0.45-1.11) and 0.68 (95% CI=0.36-1.29), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Within the range of intervals from ITS administration to calving observed in this study, there was no association with the odds of clinical mastitis in the first 30 days of lactation in dairy heifers. This study suggests that veterinary clinics may be able to extend their ITS administration service and treat dairy heifers earlier than the current recommendation of approximately 4 weeks before the planned start of calving.

Large regional shortwave forcing by anthropogenic methane informed by Jovian observations.

Recently, it was recognized that widely used calculations of methane radiative forcing systematically underestimated its global value by 15% by omitting its shortwave effects. We show that shortwave forcing by methane can be accurately calculated despite considerable uncertainty and large gaps in its shortwave spectroscopy. We demonstrate that the forcing is insensitive, even when confronted with much more complete methane absorption spectra extending to violet light wavelengths derived from observations of methane-rich Jovian planets. We undertake the first spatially resolved global calculations of this forcing and find that it is dependent on bright surface features and clouds. Localized annual mean forcing from preindustrial to present-day methane increases approaches +0.25 W/m2, 10 times the global annualized shortwave forcing and 43% of the total direct CH4 forcing. Shortwave forcing by anthropogenic methane is sufficiently large and accurate to warrant its inclusion in historical analyses, projections, and mitigation strategies for climate change.

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS.

Role of activity-dependent BDNF expression in hippocampal-prefrontal cortical regulation of behavioral perseverance.

Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal-PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders.

Viral infections of the skin: clinical features and treatment options.

Viral infections of the skin can cause significant distress and embarrassment for people who are affected. This article explores four specific viral infections that manifest on the skin: herpes simplex, herpes zoster, viral warts and molluscum contagiosum. It describes the presentation and appearance of the virus as it affects the skin and what can be done to minimise the spread of the virus. Management options are considered, although many of these conditions are self-limiting.

A critical review and meta-analysis of the efficacy of whole-cell killed Tritrichomonas foetus vaccines in beef cattle.

This review assesses the efficacy of whole cell Tritrichomonas foetus vaccine to prevent and treat trichomoniasis in beef cattle. Three databases were searched in June 2012. Eligible studies compared infection risk, open risk, and abortion risk in heifers or infection risk in bulls that received vaccine compared with no vaccine. Study results were extracted, summary effect measures were calculated, and the quality of the evidence was assessed. From 334 citations identified, 10 were relevant to the review. For heifers, there was limited evidence of moderate quality to assess the impact of vaccination on infection risk (RR, 0.89; P = .16; 95% CI, 0.76-1.05; 6 randomized and 4 nonrandomized studies; 251 animals) and open risk (RR, 0.80; P = .06; 95% CI, 0.63-1.01; 6 randomized and 5 nonrandomized studies; 570 animals). The quality of the body of work describing the impact of vaccination on abortion risk was low (summary RR, 0.57; P = .0003; 95% CI, 0.42-0.78; 3 randomized and 2 nonrandomized studies; 176 animals). The quality of evidence was very low for duration of infection (mean difference, -23.42; P = .003; 95% CI, -38.36 to -7.85; 2 randomized and 3 nonrandomized studies; 163 animals). Although the summary effect measures suggest a benefit to vaccination, due to publication bias the effect reported here is likely an over estimate of efficacy. For bull-associated outcomes, the evidence base was low or very low quality.

Accelerated integrated science sequence: an interdisciplinary introductory course for science majors.

We report here on our development of an introductory science course sequence that integrates biology, chemistry and physics in order to foster an interdisciplinary perspective in future science majors. Accelerated Integrated Science Sequence (AISS) is a two semester, double credit sequence co-taught by a biologist, a physicist and a chemist to first year undergraduates who plan to major in a natural science field. Topics are organized within a thematic framework. The course sequence also features integration of various pedagogical approaches as students shift from one type of activity to another within the same class session. The presence of AISS in our curriculum over the past five years has been correlated with increased recruitment and graduation of students in science majors and a perception within the department that AISS has helped improve the culture of learning. These benefits outweigh the difficulties of developing such a course and encourage us that interdisciplinary introductory courses can make important contributions to training versatile scientists.

The impact of local surface changes in Borneo on atmospheric composition at wider spatial scales: coastal processes, land-use change and air quality.

We present results from the OP3 campaign in Sabah during 2008 that allow us to study the impact of local emission changes over Borneo on atmospheric composition at the regional and wider scale. OP3 constituent data provide an important constraint on model performance. Treatment of boundary layer processes is highlighted as an important area of model uncertainty. Model studies of land-use change confirm earlier work, indicating that further changes to intensive oil palm agriculture in South East Asia, and the tropics in general, could have important impacts on air quality, with the biggest factor being the concomitant changes in NO(x) emissions. With the model scenarios used here, local increases in ozone of around 50 per cent could occur. We also report measurements of short-lived brominated compounds around Sabah suggesting that oceanic (and, especially, coastal) emission sources dominate locally. The concentration of bromine in short-lived halocarbons measured at the surface during OP3 amounted to about 7 ppt, setting an upper limit on the amount of these species that can reach the lower stratosphere.

Sagittal alignment after Bryan cervical arthroplasty.

STUDY DESIGN: Prospective, randomized, Food and Drug Administration Investigational Device Exemption trial from one study site. OBJECTIVE: Examine the radiographic sagittal alignment of the Bryan cervical disc for one-level disease. SUMMARY OF BACKGROUND DATA: Prospective, randomized studies demonstrate Bryan arthroplasty provides statistically better functional outcomes than anterior cervical discectomy and fusion. Uncontrolled case reports describe kyphosis after disc replacement. No prospective study has critically assessed sagittal alignment after cervical arthroplasty. METHODS: Forty-eight patients reviewed with a minimum follow-up of 2 years. Quantitative motion analysis determined the change in overall (C2-C7) and treatment-level sagittal alignment, disc space heights, and range of motion. RESULTS: Preoperatively, overall sagittal alignment was equivalent in the two groups. At 24-month follow-up, overall lordosis for the cohorts was not statistically different from preoperative values for each group. In addition, overall lordosis was not significantly different at 24 months when comparing Bryan patients with the fusion patients. The average change in disc angle from preoperative to immediate postoperative at the treated level in the Bryan disc group was a nonsignificant increase in lordosis of 0.92°. The anterior disc height was the same at all time points, but the posterior disc height was slightly (0.7 mm) more in the Bryan than in the fusion patients (P = 0.04). The angular range of motion in the Bryan group was statistically equivalent at all time points. At the fused levels, average range of motion decreased from 6.4° to 0.9° at 24 months (P < 0.0001). CONCLUSION: With the Bryan disc, there was an insignificant increase in lordosis of 0.9° at immediate postoperative time point. Overall cervical sagittal alignment is not different between the experimental and control populations. This prospective study does not demonstrate a clinically significant increase in segmental kyphosis after Bryan disc arthroplasty. Global cervical lordosis is statistically equivalent between arthroplasty and fusion groups at 2 years follow-up.

Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment.

Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonists or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5-6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9-11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome.

The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication.

The environmental pathogen Legionella pneumophila encodes three proteins containing F-box domains and additional protein-protein interaction domains, reminiscent of eukaryotic SCF ubiquitin-protein ligases. Here we show that the F-box proteins of L. pneumophila strain Paris are Dot/Icm effectors involved in the accumulation of ubiquitinated proteins associated with the Legionella-containing vacuole. Single, double and triple mutants of the F-box protein encoding genes were impaired in infection of Acanthamoeba castellanii, THP-1 macrophages and human lung epithelial cells. Lpp2082/AnkB was essential for infection of the lungs of A/J mice in vivo, and bound Skp1, the interaction partner of the SCF complex in mammalian cells, similar to AnkB from strain AA100/130b. Using a yeast two-hybrid screen and co-immunoprecipitation analysis we identified ParvB a protein present in focal adhesions and in lamellipodia, as a target. Immunofluorescence analysis confirmed that ectopically expressed Lpp2082/AnkB colocalized with ParvB at the periphery of lamellipodia. Unexpectedly, ubiquitination tests revealed that Lpp2082/AnkB diminishes endogenous ubiquitination of ParvB. Based on these results we propose that L. pneumophila modulates ubiquitination of ParvB by competing with eukaryotic E3 ligases for the specific protein-protein interaction site of ParvB, thereby revealing a new mechanism by which L. pneumophila may employ translocated effector proteins to promote bacterial survival.

Quality of spinal motion with cervical disk arthroplasty: computer-aided radiographic analysis.

STUDY DESIGN: Kinematic study of a single site in an investigational device exemption trial. OBJECTIVE: Evaluate the center of rotation (COR) after Bryan cervical arthroplasty and compare adjacent segment motion after cervical disk arthroplasty and fusion using validated radiographic analysis. SUMMARY OF BACKGROUND DATA: The goal of cervical arthroplasty is to reestablish spinal kinematics after anterior decompression. Excellent maintenance of range of motion has been reported for a variety of the prostheses; however, the manner the prostheses perform this task is different. A parameter that may be as important as range of motion is restoring the quality of motion. One of the important components is the COR that is easily studied biomechanically but has not been reported from in vivo studies. Furthermore, the effects on the quality of motion at adjacent levels have not been studied. The purpose of this study is to determine the quality of motion after Bryan cervical disk arthroplasty at the target level and the adjacent segments. METHODS: The first 48 patients diagnosed with single level cervical disk degenerative disease and associated myelopathy or radiculopathy from a single institution enrolled in the Bryan disk investigational device exemption trial were selected for inclusion. Twenty-two investigational patients and 26 anterior cervical discectomy and fusion controls were evaluated radiographically preoperatively and 3, 6, 12, and 24 months postoperatively. These results were analyzed using Quantitative Motion Analysis software manufactured by Medical Metrics Inc. Kinematic parameters included translation, sagittal rotation, anterior/posterior disk height, and the calculation of the COR both in the sagittal and coronal planes. RESULTS: At the arthroplasty level, the COR shifted more posterior (0.3 mm, 1% end plate width) and cephalad (4.9 mm, 20% end plate width) compared with the preoperative position, however, this change was not statistically significant (P=0.06). The variability of the COR, however, was less after arthroplasty compared with preoperative values. There was no significant difference in the short term between the adjacent levels after fusion compared with the prosthesis. At later time points (12 and 24 mo), however, the COR was significantly posterior at the level above arthroplasty compared with fusion (P<0.01). COR X was not significantly (P>0.3) different below fusions compared with arthroplasty. Sagittal rotation significantly increased at the level above for both the fusion and prosthesis groups. A trend was noted for increased translation (2.5% end plate width) at the level above a fusion compared with the Bryan disk at 24 months postoperatively, but this did not reach statistical significance. CONCLUSIONS: Sagittal rotation increases above the level of the arthroplasty and fusion. In the long term, the arthroplasty group had a more posterior COR at the level above, compared with the level above a fusion. Translation at the level above a fusion was slightly increased but not statistically compared with the level above the arthroplasty with similar amounts of sagittal rotation (flexion/extension). Although not reaching statistical significance, the COR seemed to shift more posterior and cephalad at the arthroplasty level with less variability compared with the preoperative position.

MicroRNAs and glioblastoma; the stem cell connection.

Recent data draw close parallels between cancer, including glial brain tumors, and the biology of stem and progenitor cells. At the same time, it has become clear that one of the major roles that microRNAs play is in the regulation of stem cell biology, differentiation, and cell 'identity'. For example, microRNAs have been increasingly implicated in the regulation of neural differentiation. Interestingly, initial studies in the incurable brain tumor glioblastoma multiforme strongly suggest that microRNAs involved in neural development play a role in this disease. This encourages the idea that certain miRs allow continued tumor growth through the suppression of differentiation and the maintenance of the stem cell-like properties of tumor cells. These concepts will be explored in this article.

Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex.

Transcription of Bdnf is controlled by multiple promoters, which drive expression of multiple transcripts encoding for the same protein. Promoter IV contributes significantly to activity-dependent brain-derived neurotrophic factor (BDNF) transcription. We have generated promoter IV mutant mice (BDNF-KIV) by inserting a GFP-STOP cassette within the Bdnf exon IV locus. This genetic manipulation results in disruption of promoter IV-mediated Bdnf expression. BDNF-KIV animals exhibited significant deficits in GABAergic interneurons in the prefrontal cortex (PFC), particularly those expressing parvalbumin, a subtype implicated in executive function and schizophrenia. Moreover, disruption of promoter IV-driven Bdnf transcription impaired inhibitory but not excitatory synaptic transmission recorded from layer V pyramidal neurons in the PFC. The attenuation of GABAergic inputs resulted in an aberrant appearance of spike-timing-dependent synaptic potentiation (STDP) in PFC slices derived from BDNF-KIV, but not wild-type littermates. These results demonstrate the importance of promoter IV-dependent Bdnf transcription in GABAergic function and reveal an unexpected regulation of STDP in the PFC by BDNF.

Use of domestic detergents in the California mastitis test for high somatic cell counts in milk.

The California mastitis test (CMT) is used on farms to identify subclinical mastitis by an indirect estimation of the somatic cell count (SCC) in milk. Four commercially available detergents were compared with a bespoke cmt fluid for their ability to detect milk samples with a scc above 200,000 cells/ml; differences between the interpretation of the results of the tests by eight operators were also investigated. The sensitivity and specificity of the test were affected by the type of detergent, and by the operators' interpretations. When used by the most sensitive operator, suitably diluted Fairy Liquid performed almost identically to cmt fluid in identifying milk samples with more than 200,000 cells/ml. The average sensitivities achieved by the eight operators for detecting this threshold were 82 per cent for Fairy Liquid and 84 per cent for cmt fluid, and the specificities were 93 and 91 per cent respectively. The other detergents contained less anionic surfactants and were less sensitive but similarly specific.

Cervical disc arthroplasty compared with arthrodesis for the treatment of myelopathy.

BACKGROUND: Although there have been case reports describing the use of cervical disc arthroplasty for the treatment of myelopathy, there is a concern that motion preservation may maintain microtrauma to the spinal cord, negatively affecting the clinical results. As we are not aware of any studies on the use of arthroplasty in this scenario, we performed a cross-sectional analysis of two large, prospective, randomized multicenter trials to evaluate the efficacy of cervical disc arthroplasty for the treatment of myelopathy. METHODS: The patients in the current study were a cohort of patients who were enrolled in the United States Food and Drug Administration Investigational Device Exemption studies of the Prestige ST and Bryan disc replacements (Medtronic, Memphis, Tennessee). The inclusion criteria were myelopathy and spondylosis or disc herniation at a single level from C3 to C7. Clinical outcome measures were collected preoperatively and at six weeks, three months, six months, twelve months, and twenty-four months postoperatively. RESULTS: A total of 199 patients were included in the present study; 106 patients (53%) underwent arthroplasty, whereas ninety-three (47%) underwent arthrodesis. The Neck Disability Index, Short Form-36 scores, and specific arm and neck pain scores improved significantly from baseline at all time points. Patients in all four groups had improvement in the postoperative neurological status and gait function; at twenty-four months after surgery, 90% (95% confidence interval, 77.8% to 96.6%) of the patients in the arthroplasty group and 81% (95% confidence interval, 64.9% to 92.0%) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Prestige ST trial and 90% (95% confidence interval, 75.8% to 97.1%) of the patients in the arthroplasty group and 77% (95% confidence interval, 57.7% to 90.1%) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Bryan trial. CONCLUSIONS: We found that patients in both the arthroplasty and arthrodesis groups had improvement following surgery; furthermore, improvement was similar between the groups, with no worsening of myelopathy in the arthroplasty group. While the findings at two years postoperatively suggest that arthroplasty is equivalent to arthrodesis for the treatment of cervical myelopathy for a single-level abnormality localized to the disc space, the present study did not evaluate the treatment of retrovertebral compression as occurs in association with ossification of the posterior longitudinal ligament, and we cannot comment upon the treatment of this condition.

Aggressive papillary glioneuronal tumor: case report and literature review.

Papillary glioneuronal tumors (PGNT) are a rare, recently described form of mixed neoplasm composed of glial and neuronal components. PGNT usually occur in children and young adults, and typically demonstrate low-grade pathology, with a low proliferative index of 1-3%. Here we describe a newly diagnosed case of PGNT with a more aggressive phenotype that required irradiation and chemotherapy. The patient was a 19-year-old female who developed progressive headaches and visual seizures. An MRI revealed a heterogeneously enhancing solid mass in the left temporo-occipital region, with significant surrounding edema and mass effect. The mass was resected under stealth guidance without complication. Postoperative MRI scans showed patchy enhancement and residual T2 and FLAIR abnormality. Pathology revealed a highly cellular neoplasm with papillary-like structures, containing cells with glial and neuronal differentiation. Regions of mitoses and focal necrosis were noted, along with a Ki-67 labeling index of 26%. The diagnosis was aggressive PGNT, and treatment consisted of conformal irradiation and concomitant temozolomide over 6 weeks. Postirradiation follow-up MRI scans demonstrated a reduction of residual enhancement and FLAIR abnormality. The patient continues standard-dose adjuvant temozolomide on a monthly basis, with further improvement on subsequent MRI scans and a stable neurologic exam. This patient demonstrates that PGNT may, in rare cases, display an aggressive clinicopathologic phenotype that requires a therapeutic approach more consistent with a high-grade glioma.