Molecular cloning and expression analysis of myd88 from oriental weatherfish (Misgurnus anguillicaudatus) in response to bacterial challenge.

Myeloid differentiation factor 88 (Myd88) plays an important role in both innate and adaptive immune response. In this study, the full-length complementary DNA (cDNA) of myd88 from Misgurnus anguillicaudatus was characterized. The myd88 cDNA is 1333 bp in length and contains an 855 bp open reading frame encoding a predicted protein of 284 amino acids. The predicted protein possesses typical Myd88 domain structural features including a death domain in the N-terminus, and box 1, 2, and 3 motifs of the Toll/IL-1 receptor domain in the C-terminus. Quantitative real-time PCR (qRT-PCR) revealed that myd88 messenger RNA (mRNA) was ubiquitously expressed in all examined tissues, especially highly in brain, kidney, blood, intestines and liver. qRT-PCR and western blotting were used to determine the mRNA and protein levels of Myd88 after Aeromonas veronii challenge, respectively. The Myd88 was remarkably upregulated in response to infection of A. veronii. These results suggested that Myd88 may play a vital role during the immune response of M. anguillicaudatus against bacterial infection.

Antibacterial Activity of Senkyunolide A Isolated from Cnidium Officinale Extract.

In this study, we investigated the antibacterial and anti-inflammatory properties of Cnidium officinale hexane (COH) extract and senkyunolide A (SA). The antibacterial activities were measured using the paper disk diffusion method and minimum inhibitory concentration (MIC) against Propionibacterium acnes and Malassezia furfur. COH extract showed antibacterial activity at a concentration of 50 mg ml-1. The MICs of COH and SA were determined using the broth microdilution method. COH was found to be active on all the bacteria tested (10 ≤ MIC ≤ 20 mg ml-1). SA showed antibacterial activity against P. acnes. The anti-inflammatory properties were determined using a pancreatic lipase inhibition activity method, lipoxygenase inhibition activity, and inhibition of nitric oxide production activity. COH and SA inhibited the production of nitric oxide by up to 50 µg ml-1 in a dose-dependent manner. COH and SA possess antibacterial and anti-inflammatory activities. They could be used as antibacterial ingredients in various industries.

Post-Traumatic Epilepsy and Seizure Susceptibility in Rat Models of Penetrating and Closed-Head Brain Injury.

Traumatic brain injury (TBI) carries a risk of developing post-traumatic epilepsy (PTE). Currently, animal models that replicate clinical PTE (delayed spontaneous and recurrent seizures) are limited, which hinders pre-clinical research. In this study, we used two rat models of penetrating ballistic-like brain injury (PBBI) and closed-head injury (CHI) to induce spontaneous seizures and also measure changes in seizure susceptibility. In the PBBI model, two trajectories (frontal and lateral) and two injury severities for each trajectory, were evaluated. In the CHI model, a single projectile impact to the dorsal/lateral region of the head was tested. Continuous video-electroencephalographic (EEG) recordings were collected for 10 days at 1 or 6 month(s) post-injury. After EEG recording, all rats were given a sub-convulsant dose of pentylenetetrazole (PTZ) to challenge the seizure susceptibility. The video-EEG recording did not detect PTE following the PBBI. Only one CHI rat demonstrated persistent and recurrent non-convulsive seizures detected at 6 months post-injury. However, after PTZ challenge, 50-100% of the animals across different TBI groups experienced seizures. Seizure susceptibility increased over time from 1 to 6 months post-injury across the majority of TBI groups. Injury severity effects were not apparent within the PBBI model, but were evident between PBBI and CHI models. These results demonstrated the difficulties in detecting delayed spontaneous post-traumatic seizures even in a high-risk model of penetrating brain injury. The PTZ-induced increase in seizure susceptibility indicated the existence of vulnerable risk of epileptogenesis following TBI, which may be considered as an alternative research tool for pre-clinical studies of PTE.

Using components of the Glasgow coma scale and Rotterdam CT scores for mortality risk stratification in adult patients with traumatic brain injury: A preliminary study.

OBJECTIVE: The Glasgow Coma Scale (GCS) and Rotterdam Computed Tomography Score (RCTS) are widely used to predict outcomes after traumatic brain injury (TBI). The objective of this study was to determine whether the GCS and RCTS components can be used to predict outcomes in patients with traumatic intracranial hemorrhage (IH) after TBI. PATIENTS AND METHODS: Between May 2009 and July 2017, 773 patients with IH after TBI were retrospectively reviewed. Data on initial GCS, RCTS according to initial brain CT, and status at hospital discharge and last follow-up were collected. Logistic regression analysis was performed to evaluate the relationship between GCS and RCTS components with outcomes after TBI. RESULTS: Among the 773 patients, the overall in-hospital mortality rate was 14.0%. Variables independently associated with outcomes were the verbal (V-GCS) and motor components of GCS (M-GCS), epidural mass lesion (E-RCTS) and intraventricular or subarachnoid hemorrhage components of RCTS (H-RCTS) (p < 0.0001). The new TBI score was obtained with the following calculation: [V-GCS + M-GCS] - [E-RCTS + H-RCTS]. CONCLUSION: The new TBI score includes both clinical status and radiologic findings from patients with IH after TBI. The new TBI score is a useful tool for assessing TBI patients with IH in that it combines the GCS and RCTS components that increases area under the curve for predicting in-hospital mortality and unfavorable outcomes and eliminates the paradoxical relationship with outcomes which was observed in GCS score. It allows a practical method to stratify the risk of outcomes after TBI.

A Feasibility Study on Timber Moisture Monitoring Using Piezoceramic Transducer-Enabled Active Sensing.

In recent years, the piezoceramic transducer-enabled active sensing technique has been extensively applied to structural damage detection and health monitoring, in civil engineering. Being abundant and renewable, timber has been widely used as a building material in many countries. However, one of the more challenging applications of timber, in construction, is the potential damage caused by moisture. Increased moisture may cause easier warping of timber components and encourage corrosion of integrated metal members, on top of potentially causing rot and decay. However, despite numerous efforts to inspect and monitor the moisture content of timber, there lacks a method that can provide truly real time, quantitative, and non-invasive measurement of timber moisture. Thus, the research presented in this paper investigated the feasibility of moisture-content monitoring using an active sensing approach, as enabled by a pair of the Lead Zirconate Titanate (PZT) transducers bonded on the surface of a timber specimen. Using a pair of transducers in an active sensing scheme, one patch generated a designed stress wave, while another patch received the signal. While the active sensing was active, the moisture content of the timber specimen was gradually increased from 0% to 60% with 10% increments. The material properties of the timber correspondingly changed under varying timber moisture content, resulting in a measurable differential in stress wave attenuation rates among the different specimens used. The experimental results indicated that the received signal energy and the moisture content of the timber specimens show a parabolic relationship. Finally, the feasibility and reliability of the presented method, for monitoring timber moisture content, are discussed.

Physical properties of root cementum: Part 27. Effect of low-level laser therapy on the repair of orthodontically induced inflammatory root resorption: A double-blind, split-mouth, randomized controlled clinical trial.

INTRODUCTION: The purpose of this 2-arm-parallel split-mouth trial was to investigate the effect of low-level laser therapy (LLLT) on the repair of orthodontically induced inflammatory root resorption (OIIRR). METHODS: Twenty patients were included in this study, with 1 side randomly assigned to receive LLLT, and the other side served as a sham. Eligibility criteria included need for bilateral maxillary first premolar extractions as part of fixed appliance treatment. OIIRR was generated by applying 150 g of buccal tipping force on the maxillary first premolars for 4 weeks. After the active force was removed, the teeth were retained for 6 weeks. LLLT commenced with weekly laser applications using a continuous beam 660-nm, 75-mW aluminum-gallium-indium-phosphorus laser with 1/e2 spot size of 0.260 cm2, power density of 0.245 W/cm2, and fluence of 3.6 J/cm2. Contact application was used at 8 points buccally and palatally above the mucosa over each tooth root for 15 seconds with a total treatment time of 2 minutes. After 6 weeks, the maxillary first premolars were extracted and scanned with microcomputed tomography for primary outcome OIIRR calculations. Subgroup analysis included assessment per root surface, per vertical third, and sites of heaviest compressive forces (buccal-cervical and palato-apical). Randomization was generated using www.randomization.com, and allocation was concealed in sequentially numbered, opaque, sealed envelopes. Blinding was used for treatment and outcome assessments. Two-tailed paired t tests were used to determine whether there were any statistically significant differences in total crater volumes of the laser vs the sham treated teeth. RESULTS: Total crater volumes were 0.746 mm3 for the laser treated teeth and 0.779 mm3 for the sham. There was a mean difference of 0.033 ± 0.39 mm3 (95% CI, -0.21 to 0.148 mm3) greater resorption crater volume in the sham group compared with the laser group; this was not statistically significant (P = 0.705). No harm was observed. CONCLUSIONS: No significant difference was found between LLLT and sham control groups in OIIRR repair.

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma

Purpose: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). Methods/patients: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). Results: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. Conclusions: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor

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Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma.

PURPOSE: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). METHODS/PATIENTS: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). RESULTS: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. CONCLUSIONS: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

Deep-Inspiration Breath-Hold Intensity Modulated Radiation Therapy to the Mediastinum for Lymphoma Patients: Setup Uncertainties and Margins.

PURPOSE: Patient setup for treating large target volumes can be challenging. In the present study, we measured the local uncertainties in the treatment of mediastinal lymphoma and investigated the need for region-specific planning target volume (PTV) margins. METHODS AND MATERIALS: The data from 30 patients who had undergone radiation therapy for mediastinal lymphoma were retrospectively analyzed. A computed tomography (CT)-on-rails (CTOR) system in the treatment room was used for daily image guidance. The total PTV was split into 6 regions: neck, supraclavicular fossa, axilla, mediastinum, upper heart, and lower heart. The total PTV and the 6 local regions were separately aligned to the planning CT scan using automatic rigid registration. The residual local errors using 3 setup strategies were investigated: no image guidance, CTOR setup to total PTV, and simulated cone beam CT setup to the mediastinum. Errors were recorded in the anteroposterior, superoinferior, and right-left directions separately. Using the residual error calculations, the margins required to cover 95% of the clinical target volume for 90% of the patients was estimated. RESULTS: For each patient, 12 to 21 days of daily CTOR data were available for analysis. The residual errors for the total PTV and mediastinum setups were both smaller than those with no image guidance. The lower heart region had more uncertainty with all 3 setup strategies. Margin analysis revealed that the magnitude of the margin is dependent on the imaging strategy, direction, and local region inside the PTV. Margins >7 mm are necessary to account for uncertainty in the neck, lower heart, and axilla regions even under daily CT guidance. CONCLUSIONS: Setup uncertainties in the mediastinum are not uniform and are dependent on target location and imaging strategy. However, with the appropriate margin, we can target regions that might not be visualized with the available on-board imager system.

A Case of Brown-Vialetto-Van Laere Syndrome Due To a Novel Mutation in SLC52A3 Gene: Clinical Course and Response to Riboflavin.

Brown-Vialetto-Van Laere syndrome is a rare disorder characterized by motor, sensory, and cranial neuronopathies, associated with mutations in SLC52A2 and SLC52A3 genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. The authors describe the clinical course of a 6-year-old girl with Brown-Vialetto-Van Laere syndrome and a novel homozygous mutation c.1156T>C in the SLC52A3 gene, who presented at the age of 2.5 years with progressive brain stem dysfunction including ptosis, facial weakness, hearing loss, dysphagia, anarthria with bilateral vocal cord paralysis, and ataxic gait. She subsequently developed respiratory failure requiring tracheostomy and worsening dysphagia necessitating a gastrostomy. Following riboflavin supplementation, resolution of facial diplegia and ataxia, improvements in ptosis, and bulbar function including vocalization and respiration were noted. However, her sensorineural hearing loss remained unchanged. Similar to other cases of Brown-Vialetto-Van Laere syndrome, our patient responded favorably to early riboflavin supplementation with significant but not complete neurologic recovery.

Concurrent hyperthermia and re-irradiation for recurrent high-grade gliomas.

Salvage therapy for recurrent high grade gliomas (HGG) includes surgery, radiotherapy and chemotherapy, however, standard treatment does not exist. We evaluated the tolerability and efficacy of re-irradiation (re-RT) with hyperthermia (HT) for patients with recurrent HGG. From September 2010 to July 2015, 20 patients with recurrent HGG were treated with re-RT and HT. The radiotherapy dose of 30 Gray (Gy) was delivered with 2 Gy per fraction daily, and HT was performed twice weekly. Primary endpoints were treatment compliance and toxicity. Second endpoints were overall survival (OS) and progression free survival (PFS). The median interval between initial RT and re-RT was 11 months. During re-RT with HT, there were no significant acute morbidities over grade 3. Median overall survival (OS) from re-irradiation was 8.4 months and the 6 and 12 months survival rate were 67% and 30%, respectively. The median progression free survival (PFS) from re-irradiation was 4.1 month. Our findings suggested that concurrent re-RT with HT was a safe and well-tolerated. In addition, the combination re-RT and HT could be a valuable salvage treatment option for selected recurrent HGG patients with poor performance status.

Combination therapy of levetiracetam and gabapentin against nonconvulsive seizures induced by penetrating traumatic brain injury.

BACKGROUND: Posttraumatic seizures are a medical problem affecting patients with traumatic brain injury. Yet effective treatment is lacking owing to the limitations of antiepileptic drugs (AEDs) applicable to these patients. METHODS: In this study, we evaluated the dose-response efficacy of levetiracetam (12.5-100.0 mg/kg) and gabapentin (1.25-25.0 mg/kg) administered either individually or in pairs at fixed-dose ratios as a combination in mitigating posttraumatic nonconvulsive seizures induced by severe penetrating ballistic-like brain injury (PBBI) in rats. Seizures were detected by continuous electroencephalogram (EEG) monitoring for 72 hours postinjury. Animals were treated twice per day for 3 days by intravenous injections. RESULTS: Both levetiracetam (25-100 mg/kg) and gabapentin (6.25-25 mg/kg) significantly reduced PBBI-induced seizure frequency by 44% to 73% and 61% to 69%, and seizure duration by 45% to 64% and 70% to 78%, respectively. However, the two drugs manifested different dose-response profiles. Levetiracetam attenuated seizure activity in a dose-dependent fashion, whereas the beneficial effects of gabapentin plateaued across the three highest doses tested. Combined administration of levetiracetam and gabapentin mirrored the more classic dose-response profile of levetiracetam monotherapy. However, no additional benefit was derived from the addition of gabapentin. Furthermore, isobolographic analysis of the combination dose-response profile of levetiracetam and gabapentin failed to reach the expected level of additivity, suggesting an unlikelihood of favorable interactions between these two drugs against spontaneously occurring posttraumatic seizure activities at the particular set of dose ratios tested. CONCLUSION: This study was the first attempt to apply isobolographic approach to studying AED combination therapy in the context of spontaneously occurring posttraumatic seizures. Despite the failure to achieve additivity from levetiracetam and gabapentin combination, it is important to recognize the objectivity of the isobolographic approach in the evaluation of AED combination therapy against seizures directly associated with brain injuries.

Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-γ (PPARγ) are disrupted by retinal disease-associated mutations.

Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the nuclear receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand-binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of peroxisome proliferator-activated receptor-γ (PPARγ)/NR1C3 and thyroid hormone receptor b (TRb) TRß/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARα/NR1C1 or PPARδ/NR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild-type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary, our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRß that have potential importance in retinal development and disease.

Characterizing Attention with Predictive Network Models.

Recent work shows that models based on functional connectivity in large-scale brain networks can predict individuals' attentional abilities. While being some of the first generalizable neuromarkers of cognitive function, these models also inform our basic understanding of attention, providing empirical evidence that: (i) attention is a network property of brain computation; (ii) the functional architecture that underlies attention can be measured while people are not engaged in any explicit task; and (iii) this architecture supports a general attentional ability that is common to several laboratory-based tasks and is impaired in attention deficit hyperactivity disorder (ADHD). Looking ahead, connectivity-based predictive models of attention and other cognitive abilities and behaviors may potentially improve the assessment, diagnosis, and treatment of clinical dysfunction.

TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication.

OBJECTIVE: We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. DESIGN: We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. RESULTS: We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. CONCLUSIONS: Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.

Bunch-by-bunch position measurement and analysis at PLS-II.

A bunch-by-bunch measurement system has been developed at Pohang Light Source II. The system consists of a four-channel button pick-up, 20 GHz sampling oscilloscope and an 800 MHz low-pass digital filter. Upon measuring a bunch-by-bunch spatio-temporal beam motion matrix over many turns, singular-value decomposition analysis is used to reveal the dominant coupled-bunch modes. The system can diagnose injection oscillations due to kicker errors and the effect of resistive-wall impedance that gives rise to instability during operation.

Study on the Mechanism of Health Protection of Mongolian Medicine Polyginatum Odoratum / Монголын эм зүй, эм судлал

Objective: To explore the effects of Polygonatum odoratum on body based on metabonomics. Methods: The ultra performance liquid chromatography coupled with mass spectrometry (UPLC-MS) and principle component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to evaluate the changes of endogenous substances in rats after intragastric administration of Polygonatum odoratum. Results: Significant differences between the control group and administration group were observed in PCA and OPLS-DA model. Five potential biomarkers between control group and administration group were identified. The relative content of Alpha-Tocotrienol, PC(14:1(9Z)/14:1(9Z)), Stearic acid, Theasapogenol A, Docosahexaenoic acid increased. Conclusion: The biomarkers had many beneficial activities, so the Mongolian medicine Polygonatum odoratum had the function of health care. Key words: Mongolian drug; Polygonatum odoratum; Biomarkers; UPLC-MS

Impact of paraaortic lymphadenectomy for endometrial cancer with positive pelvic lymph nodes: A Korean Radiation Oncology Group study (KROG 13-17).

AIM: We investigated the role of paraaortic lymph node dissection (PALND) in patients with stage IIIC1 endometrial carcinoma after surgery followed by adjuvant radiotherapy (RT) alone or chemoradiotherapy (CTRT). METHODS: We performed a subgroup analysis in 151 patients treated with adjuvant pelvic RT. Paraaortic-recurrence free survival, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: In adjuvant RT alone, PALND was significantly related to reduced risk of paraaortic recurrence (0% vs. 17.1%) and distant metastasis (4.5% vs. 19.5%) compared with the no PALND group. PALND affected 5-year DFS (90.2% vs. 58.9%, p = 0.016) and OS (100% vs. 83.1%, p = 0.022). For the CTRT group, the paraaortic recurrence rate was 19.5% for the no PALND group and 12.8% for the PALND group (p = 0.682). Of patients who underwent PALND in the CTRT group, less extensive PALND was significantly related to increased paraaortic recurrence (≤10 vs. >10 dissected LNs, 17.1% vs. 0%). In the no PALND group (n = 82), 5-year paraaortic-recurrence free survival was 79.4% for the CTRT group and 76.2% for the RT alone group (p = 0.941). In multivariate analysis, PALND was significantly associated with reduced risk of disease-specific death (HR, 0.50; 95% CI, 0.26-0.96; p = 0.037). CONCLUSION: PALND provided excellent paraaortic control and improved outcome in stage IIIC1 endometrial cancer with favorable tumor features treated with adjuvant RT alone. Less extensive PALND was associated with significantly increased paraaortic recurrence in patients with advanced tumor features treated with adjuvant CTRT. Combined CTRT did not affect disease control in the paraaortic region compared with RT alone.

Neuroprotection and anti-seizure effects of levetiracetam in a rat model of penetrating ballistic-like brain injury.

PURPOSE: We assessed the therapeutic efficacy of FDA-approved anti-epileptic drug Levetiracetam (LEV) to reduce post-traumatic nonconvulsive seizure (NCS) activity and promote neurobehavioral recovery following 10% frontal penetrating ballistic-like brain injury (PBBI) in male Sprague-Dawley rats. METHODS: Experiment 1 anti-seizure study: 50 mg/kg LEV (25 mg/kg maintenance doses) was given twice daily for 3 days (LEV3D) following PBBI; outcome measures included seizures incidence, frequency, duration, and onset. Experiment 2 neuroprotection studies: 50 mg/kg LEV was given twice daily for either 3 (LEV3D) or 10 days (LEV10D) post-injury; outcome measures include motor (rotarod) and cognitive (water maze) functions. RESULTS: LEV3D treatment attenuated seizure activity with significant reductions in NCS incidence (54%), frequency, duration, and delayed latency to seizure onset compared to vehicle treatment. LEV3D treatment failed to improve cognitive or motor performance; however extending the dosing regimen through 10 days post-injury afforded significant neuroprotective benefit. Animals treated with the extended LEV10D dosing regimen showed a twofold improvement in rotarod task latency to fall as well as significantly improved spatial learning performance (24%) in the MWM task. CONCLUSIONS: These findings support the dual anti- seizure and neuroprotective role of LEV, but more importantly identify the importance of an extended dosing protocol which was specific to the therapeutic targets studied.