Publications by authors named "Brandon Miller"

74 Publications

Cyclic Thiosulfinates as a Novel Class of Disulfide Cleavable Cross-Linkers for Rapid Hydrogel Synthesis.

Bioconjug Chem 2021 Feb 19. Epub 2021 Feb 19.

Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.

We recently reported that cyclic thiosulfinates are cysteine selective cross-linkers that avoid the "dead-end" modifications that contribute to other cross-linkers' toxicity. In this study, we generalize the chemistry of cyclic thiosulfinates to that of thiol selective cross-linking and apply them to the synthesis of hydrogels. Thiol-functionalized four-arm poly(ethylene glycol) and hyaluronic acid monomers were cross-linked with 1,2-dithiane-1-oxide to form disulfide cross-linked hydrogels within seconds. The synthesized hydrogel could be reduced with physiological concentrations of glutathione, which modulated hydrogel mechanical properties and degradation kinetics. Bovine serum albumin protein was successfully encapsulated in hydrogel, and diffusion-mediated release was demonstrated in vitro. Hep G2 cells grew in the presence of preformed hydrogel and during hydrogel synthesis, demonstrating acceptable cytotoxicity. We encapsulated cells within a hydrogel and demonstrated cell growth and recovery up to 10 days, with and without cell adhesion peptides. In summary, we report cyclic thiosulfinates as a novel class of cross-linkers for the facile synthesis of biodegradable hydrogels.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00049DOI Listing
February 2021

Hemoglobin induces oxidative stress and mitochondrial dysfunction in oligodendrocyte progenitor cells.

Transl Res 2021 Jan 15. Epub 2021 Jan 15.

Department of Neurosurgery, University of Kentucky, Lexington, Kentucky; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky. Electronic address:

Oligodendrocyte progenitor cells (OPCs) in the infant brain give rise to mature oligodendrocytes that myelinate CNS axons. OPCs are particularly vulnerable to oxidative stress that occurs in many forms of brain injury. One common cause of infant brain injury is neonatal intraventricular hemorrhage (IVH), which releases blood into the CSF and brain parenchyma of preterm infants. Although blood contains the powerful oxidant hemoglobin, the direct effects of hemoglobin on OPCs have not been studied. We utilized a cell culture system to test if hemoglobin induced free radical production and mitochondrial dysfunction in OPCs. We also tested if phenelzine (PLZ), an FDA-approved antioxidant drug, could protect OPCs from hemoglobin-induced oxidative stress. OPCs were isolated from Sprague Dawley rat pups and exposed to hemoglobin with and without PLZ. Outcomes assessed included intracellular reactive oxygen species levels using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent dye, oxygen consumption using the XFe96 Seahorse assay, and proliferation measured by BrdU incorporation assay. Hemoglobin induced oxidative stress and impaired mitochondrial function in OPCs. PLZ treatment reduced hemoglobin-induced oxidative stress and improved OPC mitochondrial bioenergetics. The effects of hemoglobin and PLZ on OPC proliferation were not statistically significant, but showed trends towards hemoglobin reducing OPC proliferation and PLZ increasing OPC proliferation (P=0.06 for both effects). Collectively, our results indicate that hemoglobin induces mitochondrial dysfunction in OPCs and that antioxidant therapy reduces these effects. Therefore, antioxidant therapy may hold promise for white matter diseases in which hemoglobin plays a role, such as neonatal IVH.
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http://dx.doi.org/10.1016/j.trsl.2021.01.005DOI Listing
January 2021

Synthesis of polymer nanoparticles via electrohydrodynamic emulsification-mediated self-assembly.

J Colloid Interface Sci 2021 Mar 28;586:445-456. Epub 2020 Oct 28.

William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 W. Woodruff Ave., Columbus, OH 43210, USA; Department of Biomedical Engineering, The Ohio State University, 151 W. Woodruff Ave., Columbus, OH 43210, USA. Electronic address:

Hypothesis: Electrospray can rapidly produce fine, organic solvent-in-water emulsions in the absence of surfactant via electrohydrodynamic emulsification (EE), a reverse configuration of traditional electrospray. This paper investigates whether EE can produce high-quality nanocomposites comprised of block co-polymers and organic nanoparticles (NPs) via the interfacial instability (IS) self-assembly method. Surfactant-free approaches may increase encapsulation efficiency and product uniformity, process speed, and ease of downstream product purification.

Experiments: All particles were produced using EE-mediated self-assembly (SA) (EE-SA). Particles were produced using poly(lactic-co-glycolic acid) (PLGA) polymers as proof of concept. Then, block copolymer (BCP) micelles were synthesized from polystyrene-block-poly(ethylene oxide) (PS-b-PEO) (PS 9.5 kDa:PEO 18.0 kDa) in the presence and absence of superparamagnetic iron oxide nanoparticles (SPIONs) or quantum dots (QDs). Encapsulant concentration was varied, and the effect of encapsulant NP ligands on final particle size was investigated.

Findings: EE-SA generated both pure polymer NPs and nanocomposites containing SPIONs and QDs. PLGA particles spanned from sub- to super-micron sizes. PS-b-PEO NPs and nanocomposites were highly monodisperse, and more highly loaded than those made via a conventional, surfactant-rich IS process. Free ligands decreased the size of pure BCP particles. Increasing encapsulant levels led to a morphological transition from spherical to worm-like to densely loaded structures.
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http://dx.doi.org/10.1016/j.jcis.2020.10.108DOI Listing
March 2021

Neurocognitive Outcomes in a Cisternal Blood Injection Murine Model of Subarachnoid Hemorrhage.

J Stroke Cerebrovasc Dis 2020 Nov 26;29(11):105249. Epub 2020 Aug 26.

Emory University School of Medicine, Department of Neurosurgery, Atlanta, GA, USA; Cerebrovascular Research Laboratory, Department of Neurosurgery, Atlanta, GA, USA. Electronic address:

Background: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model.

Methods: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus.

Results: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus.

Conclusions: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105249DOI Listing
November 2020

Acute brain inflammation, white matter oxidative stress, and myelin deficiency in a model of neonatal intraventricular hemorrhage.

J Neurosurg Pediatr 2020 Aug 28:1-11. Epub 2020 Aug 28.

1Departments of Neurosurgery.

Objective: Neonatal intraventricular hemorrhage (IVH) leads to posthemorrhagic hydrocephalus (PHH), brain injury, and long-term disability. Current therapy for IVH is based on treating PHH but does not address the underlying brain injury. In order to develop pharmacological treatment for IVH, there must be a better understanding of the underlying pathology of this disease. This study was designed to determine the time course of the acute inflammation and oxidative stress that may underlie the progressive pathology of IVH. The authors sought to understand the temporal relationships among inflammation, oxidative stress, and white matter pathology in a rat model of IVH.

Methods: A rat model of IVH consisting of hemoglobin injection into the lateral ventricle was used. Tissue was analyzed via biochemical and histological methods to map the spatiotemporal distribution of innate immune activation and oxidative stress. White matter was quantified using both immunohistochemistry and Western blot for myelin basic protein (MBP) in the corpus callosum.

Results: IVH led to acute induction of inflammatory cytokines, followed by oxidative stress. Oxidative stress was concentrated in white matter, adjacent to the lateral ventricles. Animals with IVH initially gained weight at a lower rate than control animals and had larger ventricles and less MBP than control animals.

Conclusions: Experimental IVH induces global inflammation throughout the brain and oxidative stress concentrated in the white matter. Both of these phenomena occur early after IVH. This has implications for human neonates with immature white matter that is exquisitely sensitive to inflammation and oxidative stress. Antiinflammatory or antioxidant therapy for IVH may need to be initiated early in order to protect developing white matter.
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http://dx.doi.org/10.3171/2020.5.PEDS20124DOI Listing
August 2020

Microscopic Manipulation of Ferroelectric Domains in SnSe Monolayers at Room Temperature.

Nano Lett 2020 Sep 24;20(9):6590-6597. Epub 2020 Aug 24.

Max Planck Institute of Microstructure Physics, Weinberg 2, Halle 06120, Germany.

Two-dimensional (2D) van der Waals ferroelectrics provide an unprecedented architectural freedom for the creation of artificial multiferroics and nonvolatile electronic devices based on vertical and coplanar heterojunctions of 2D ferroic materials. Nevertheless, controlled microscopic manipulation of ferroelectric domains is still rare in monolayer-thick 2D ferroelectrics with in-plane polarization. Here we report the discovery of robust ferroelectricity with a critical temperature close to 400 K in SnSe monolayer plates grown on graphene and the demonstration of controlled room-temperature ferroelectric domain manipulation by applying appropriate bias voltage pulses to the tip of a scanning tunneling microscope (STM). This study shows that STM is a powerful tool for detecting and manipulating the microscopic domain structures in 2D ferroelectric monolayers, which are difficult for conventional approaches such as piezoresponse force microscopy, thus facilitating the hunt for other 2D ferroelectric monolayers with in-plane polarization with important technological applications.
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http://dx.doi.org/10.1021/acs.nanolett.0c02357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498149PMC
September 2020

Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.

Oncologist 2020 08 17;25(8):e1158-e1169. Epub 2020 Jun 17.

Stefanie Spielman Comprehensive Breast Center, The Ohio State University, Columbus, Ohio, USA.

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) are U.S. Food and Drug Administration (FDA) approved for treatment of BRCA-mutated metastatic breast cancer. Furthermore, the BROCADE studies demonstrated benefit of adding an oral PARPi, veliparib, to carboplatin and paclitaxel in patients with metastatic breast cancer harboring BRCA mutation. Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay.

Materials And Methods: Patients received escalating doses of veliparib on a 7-, 14-, or 21-day schedule with carboplatin every 3 weeks. Patients underwent [18]fluoro-3'-deoxythymidine ( FLT) positron emission tomography (PET) imaging.

Results: Forty-four patients (39 TNBC, 5 HR positive/HER2 negative with a defective FA pathway) received a median of 5 cycles (range 1-36). Observed dose-limiting toxicities were grade (G) 4 thrombocytopenia (n = 4), G4 neutropenia (n = 1), and G3 akathisia (n = 1). Common grade 3-4 toxicities included thrombocytopenia, lymphopenia, neutropenia, anemia, and fatigue. Of the 43 patients evaluable for response, 18.6% achieved partial response and 48.8% had stable disease. Median progression-free survival was 18.3 weeks. RP2D of veliparib was established at 250 mg twice daily on days 1-21 along with carboplatin at area under the curve 5. Patients with partial response had a significant drop in maximum standard uptake value (SUV ) of target lesions between baseline and early in cycle 1 based on FLT-PET (day 7-21; p  = .006).

Conclusion: The combination of continuous dosing of veliparib and every-3-week carboplatin demonstrated activity and an acceptable toxicity profile. Decrease in SUV on FLT-PET scan during the first cycle of this therapy can identify patients who are likely to have a response.

Implications For Practice: The BROCADE studies suggest that breast cancer patients with BRCA mutation benefit from addition of veliparib to carboplatin plus paclitaxel. This study demonstrates that a higher dose of veliparib is tolerable and active in combination with carboplatin alone. With growing interest in imaging-based early response assessment, the authors demonstrate that decrease in [18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) SUV during cycle 1 of therapy is associated with response. Collectively, this study established a safety profile of veliparib and carboplatin in advanced breast cancer while also providing additional data on the potential for FLT-PET imaging modality in monitoring therapy response.
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http://dx.doi.org/10.1634/theoncologist.2020-0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418347PMC
August 2020

Intravenous 5-fluoro-2'-deoxycytidine administered with tetrahydrouridine increases the proportion of p16-expressing circulating tumor cells in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2020 05 20;85(5):979-993. Epub 2020 Apr 20.

Division of Cancer Treatment and Diagnosis, National Cancer Institute, 31 Center Drive, Bldg. 31 Room 3A-44, Bethesda, MD, 20892, USA.

Purpose: Following promising responses to the DNA methyltransferase (DNMT) inhibitor 5-fluoro-2'-deoxycytidine (FdCyd) combined with tetrahydrouridine (THU) in phase 1 testing, we initiated a non-randomized phase 2 study to assess response to this combination in patients with advanced solid tumor types for which tumor suppressor gene methylation is potentially prognostic. To obtain pharmacodynamic evidence for DNMT inhibition by FdCyd, we developed a novel method for detecting expression of tumor suppressor protein p16/INK4A in circulating tumor cells (CTCs).

Methods: Patients in histology-specific strata (breast, head and neck [H&N], or non-small cell lung cancers [NSCLC] or urothelial transitional cell carcinoma) were administered FdCyd (100 mg/m) and THU (350 mg/m) intravenously 5 days/week for 2 weeks, in 28-day cycles, and progression-free survival (PFS) rate and objective response rate (ORR) were evaluated. Blood specimens were collected for CTC analysis.

Results: Ninety-three eligible patients were enrolled (29 breast, 21 H&N, 25 NSCLC, and 18 urothelial). There were three partial responses. All strata were terminated early due to insufficient responses (H&N, NSCLC) or slow accrual (breast, urothelial). However, the preliminary 4-month PFS rate (42%) in the urothelial stratum exceeded the predefined goal-though the ORR (5.6%) did not. An increase in the proportion of p16-expressing cytokeratin-positive CTCs was detected in 69% of patients evaluable for clinical and CTC response, but was not significantly associated with clinical response.

Conclusion: Further study of FdCyd + THU is potentially warranted in urothelial carcinoma but not NSCLC or breast or H&N cancer. Increase in the proportion of p16-expressing cytokeratin-positive CTCs is a pharmacodynamic marker of FdCyd target engagement.
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http://dx.doi.org/10.1007/s00280-020-04073-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188725PMC
May 2020

Republished: A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus.

J Neurointerv Surg 2020 May 17;12(5):e5. Epub 2020 Mar 17.

Department of Radiology, University of Kentucky, Lexington, Kentucky, USA.

Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.
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http://dx.doi.org/10.1136/neurintsurg-2019-015631.repDOI Listing
May 2020

A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus.

BMJ Case Rep 2020 Mar 3;13(3). Epub 2020 Mar 3.

Department of Radiology, University of Kentucky, Lexington, Kentucky, USA.

Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.
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http://dx.doi.org/10.1136/bcr-2019-015631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059410PMC
March 2020

Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice.

J Neurosurg Pediatr 2020 Feb 7:1-8. Epub 2020 Feb 7.

1Department of Neurosurgery.

Objective: The authors sought to determine if hydrocephalus caused a proinflammatory state within white matter as is seen in many other forms of neonatal brain injury. Common causes of hydrocephalus (such as trauma, infection, and hemorrhage) are inflammatory insults themselves and therefore confound understanding of how hydrocephalus itself affects neuroinflammation. Recently, a novel animal model of hydrocephalus due to a genetic mutation in the Ccdc39 gene has been developed in mice. In this model, ciliary dysfunction leads to early-onset ventriculomegaly, astrogliosis, and reduced myelination. Because this model of hydrocephalus is not caused by an antecedent proinflammatory insult, it was utilized to study the effect of hydrocephalus on inflammation within the white matter of the corpus callosum.

Methods: A Meso Scale Discovery assay was used to measure levels of proinflammatory cytokines in whole brain from animals with and without hydrocephalus. Immunohistochemistry was used to measure macrophage activation and NG2 expression within the white matter of the corpus callosum in animals with and without hydrocephalus.

Results: In this model of hydrocephalus, levels of cytokines throughout the brain revealed a more robust increase in classic proinflammatory cytokines (interleukin [IL]-1β, CXCL1) than in immunomodulatory cytokines (IL-10). Increased numbers of macrophages were found within the corpus callosum. These macrophages were polarized toward a proinflammatory phenotype as assessed by higher levels of CD86, a marker of proinflammatory macrophages, compared to CD206, a marker for antiinflammatory macrophages. There was extensive structural damage to the corpus callosum of animals with hydrocephalus, and an increase in NG2-positive cells.

Conclusions: Hydrocephalus without an antecedent proinflammatory insult induces inflammation and tissue injury in white matter. Future studies with this model will be useful to better understand the effects of hydrocephalus on neuroinflammation and progenitor cell development. Antiinflammatory therapy for diseases that cause hydrocephalus may be a powerful strategy to reduce tissue damage.
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http://dx.doi.org/10.3171/2019.12.PEDS19625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415550PMC
February 2020

The Interaction of Cognitive Interference, Standing Surface, and Fatigue on Lower Extremity Muscle Activity.

Saf Health Work 2019 Sep 12;10(3):321-326. Epub 2019 Jun 12.

Mississippi State University, Department of Kinesiology, Mississippi State, MS, United States.

Background: Performing cognitive tasks and muscular fatigue have been shown to increase muscle activity of the lower extremity during quiet standing. A common intervention to reduce muscular fatigue is to provide a softer shoe-surface interface. However, little is known regarding how muscle activity is affected by softer shoe-surface interfaces during static standing. The purpose of this study was to assess lower extremity muscular activity during erect standing on three different standing surfaces, before and after an acute workload and during cognitive tasks.

Methods: Surface electromyography was collected on ankle dorsiflexors and plantarflexors, and knee flexors and extensors of fifteen male participants. Dependent electromyography variables of mean, peak, root mean square, and cocontraction index were calculated and analyzed with a 2 × 2 × 3 within-subject repeated measures analysis of variance.

Results: Pre-workload muscle activity did not differ between surfaces and cognitive task conditions. However, greater muscle activity during post-workload balance assessment was found, specifically during the cognitive task. Cognitive task errors did not differ between surface and workload.

Conclusions: The cognitive task after workload increased lower extremity muscular activity compared to quite standing, irrespective of the surface condition, suggesting an increased demand was placed on the postural control system as the result of both fatigue and cognitive task.
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http://dx.doi.org/10.1016/j.shaw.2019.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717930PMC
September 2019

Effects of Weighted Vest Loading During Daily Living Activities on Countermovement Jump and Sprint Performance.

Int J Sports Physiol Perform 2019 Oct 11:1-10. Epub 2019 Oct 11.

Purpose: Wearing a weighted vest (WV) during daily living and training can enhance jump and sprint performance; however, studies examining the efficacy of this method in female populations is limited. This study examined the effect of wearing a WV during daily living and training on countermovement jump (CMJ), change-of-direction, and sprint performance.

Methods: Trained females were separated into intervention (n = 9) and control (n = 10) groups. The intervention group wore WVs of ∼8% body mass 4 days per week for 8 hours per day (32 h/wk total), and 3 training sessions per week for the first 3 weeks. Subsequently, 3 weeks of regular training without WV stimulus was completed. The control group received no intervention and continued normal training for 6 weeks. Average and best performance was assessed on the single CMJ, four continuous CMJ, t-test change-of-direction drill, and a 25-m sprint at baseline, week 3, and week 6.

Results: No significant interactions or group effects were found. However, significant time main effects revealed increases in average rate of force development during the CMJ from baseline to week 3 (P = .048) and week 6 (P = .013), whereas peak vertical ground reaction force increased during the four continuous CMJ from baseline to week 3 (P = .048) and week 6 (P = .025) for both groups.

Conclusions: The lower relative WV load used in this study failed to elicit significant improvements in jump and sprint performance in comparison with routine training, or that which have been found in past investigations with elite male athletes completing high-intensity performance tasks with greater WV loads.
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http://dx.doi.org/10.1123/ijspp.2019-0318DOI Listing
October 2019

Standing Waves Induced by Valley-Mismatched Domains in Ferroelectric SnTe Monolayers.

Phys Rev Lett 2019 May;122(20):206402

State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing 100084, China.

Two-dimensional (2D) quasiparticle standing waves originate from the interference of coherent quantum states and are usually created by the scattering off edges, atomic steps, or adatoms that induce large potential barriers. We report standing waves close to the valence band maximum (E_{V}), confined by electrically neutral domain walls of newly discovered ferroelectric SnTe monolayers, as revealed by spatially resolved scanning tunneling spectroscopy. Ab initio calculations show that this novel confinement arises from the polarization lifted hole valley degeneracy and a ∼90° rotation of the Brillouin zones that render holes' momentum mismatched across neighboring domains. These results show a potential for polarization-tuned valleytronics in 2D ferroelectrics.
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http://dx.doi.org/10.1103/PhysRevLett.122.206402DOI Listing
May 2019

A Picture is Worth 1000 Messages: Investigating Face and Body Photos on Mobile Dating Apps for Men Who Have Sex with Men.

Authors:
Brandon Miller

J Homosex 2020 Nov 10;67(13):1798-1822. Epub 2019 May 10.

Communication Department, University of Massachusetts Boston , Boston, Massachusetts, USA.

The present study investigated the way men visually self-present on MSM-specific mobile dating app profiles, as well as the connection between visual self-presentation strategies, demographic variables, and psychosocial attitudes about masculinity and the body. In particular, emphasis was placed on two aspects of men's visual self-presentation: face-disclosure and body-disclosure. Using a selective self-presentation framework, findings indicated that the majority of men presented their face in their profile photo and that nearly one in five presented their unclothed torso. Face-disclosure was connected to higher levels of app usage, longer-term app usage, and levels of outness. The use of shirtless photos was related to age, a higher drive for muscularity, more self-perceived masculinity, and stronger anti-effeminacy attitudes. The findings are discussed in relation to both strategic self-presentation, and the distinct meanings of face and body photos within MSM online culture.
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http://dx.doi.org/10.1080/00918369.2019.1610630DOI Listing
November 2020

Comparison of manual and automated image analysis techniques for characterization of fission gas pores in irradiated U-Mo fuels.

Micron 2019 04 23;119:98-108. Epub 2019 Jan 23.

Nuclear Engineering Program, Department of Materials Science and Engineering, University of Florida, Gainesville, FL, 32611, USA. Electronic address:

Irradiation of low enriched uranium-molybdenum fuel results in the production and agglomeration of fission gas bubbles that can potentially lead to fuel failure. Manual point volume fraction counting in accordance with ASTME562 standard has been historically used to conduct pore size distribution analysis. While effective, the manual methodology is not efficient and therefore not feasible for the characterization of several fuel plates in a timely manner. In this contribution, ImageJ and MATLAB software were investigated as suitable alternatives to manual counting. Validation and verification were performed to show that the results are reproducible. Image analysis revealed insignificant variation of fission gas pore morphology with fission density. In addition, the results from two different sample preparation techniques - vibratory polishing and focused ion beam milling were compared. Sample preparation has more than 1% influence on the results of pore size distribution analysis. Comprehensive comparison identified vibratory polishing as the preferred method for conducting fission gas pore size distribution analysis.
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http://dx.doi.org/10.1016/j.micron.2019.01.008DOI Listing
April 2019

Onyx embolization of a ruptured anterior inferior cerebellar artery in a neonate.

Childs Nerv Syst 2019 02 10;35(2):373-378. Epub 2018 Sep 10.

Department of Neurosurgery, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, USA.

Aneurysmal subarachnoid hemorrhage (SAH) is rare in neonates. The authors present a unique report of a neonate with SAH from anterior inferior cerebellar artery (AICA) aneurysm rupture that was successfully treated with Onyx embolization. This case report demonstrates the utility of Onyx embolization for posterior circulation aneurysms in neonates and the successful management of SAH in this population.
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http://dx.doi.org/10.1007/s00381-018-3968-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257924PMC
February 2019

Simultaneous Selective Dorsal Rhizotomy and Baclofen Pump Removal Improve Ambulation in Patients with Spastic Cerebral Palsy.

Cureus 2018 Jun 12;10(6):e2791. Epub 2018 Jun 12.

Neurological Surgery, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, USA.

Background: Intrathecal baclofen (ITB) administration via an implanted programmable pump and selective dorsal rhizotomy (SDR) are both used for the treatment of cerebral palsy (CP) spasticity.

Objective: To examine whether SDR can improve ambulation in children who have been receiving ITB therapy for spastic cerebral palsy.

Methods: We reviewed 13 patients who received prior ITB placement with subsequent simultaneous SDR and ITB removal. Patients also completed a follow-up survey to document long-term motor function.

Results: In our 13-patient cohort, patients received ITB treatment for an average of 4.4 [Formula: see text] 1.8 years and the mean age of ITB removal/SDR was 12.5 [Formula: see text] 5.8 years. The follow-up period ranged from 3 to 19 months (mean duration: 6.9 [Formula: see text] 5 months). Pre-operatively, all patients had Gross Motor Function Classification System (GMFCS) scores between 2 and 4. Nine patients were diagnosed with spastic diplegia, two had spastic triplegia and two had spastic quadriplegia. SDR and ITB removal led to improved lower limb spasticity and ambulation. GMFCS scores remained stable in all patients. One patient developed a cerebrospinal fluid (CSF) collection in the abdominal wall due to a CSF leak from the baclofen pump site. All 11 patients who completed the follow-up survey noted improved motor function.

Conclusion: This study demonstrates that SDR can reduce spasticity and improve mobility after years of ITB treatment for spastic cerebral palsy.
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http://dx.doi.org/10.7759/cureus.2791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089480PMC
June 2018

Widely Metastatic Choroid Plexus Carcinoma Associated with Novel TP53 Somatic Mutation.

World Neurosurg 2018 Nov 9;119:233-236. Epub 2018 Aug 9.

Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: Choroid plexus carcinoma (CPC) is a rare, malignant tumor occurring more commonly in children than adults. This case report describes the clinical course of a 3-year-old boy with a rare case of metastatic CPC with a novel TP53 mutation.

Case Description: A 3-year-old boy presented with postconcussive symptoms after a fall. Computed tomography and magnetic resonance imaging revealed lesions in the suprasellar cistern, left lateral ventricle, and cauda equina. The tumor was diagnosed as choroid plexus carcinoma with a novel TP53 V216M somatic mutation. The patient underwent resection of the left lateral ventricle lesion.

Conclusion: We describe a case of CPC with highly metastatic characteristics and a novel TP53 mutation. Our report implicates TP53 in the pathogenesis of pediatric CPC, and we emphasize that CPC in children should prompt careful consideration of TP53 status to inform prognosis and clinical treatment.
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http://dx.doi.org/10.1016/j.wneu.2018.07.284DOI Listing
November 2018

Analysis and comparison of focused ion beam milling and vibratory polishing sample surface preparation methods for porosity study of U-Mo plate fuel for research and test reactors.

Micron 2018 07 2;110:57-66. Epub 2018 May 2.

Oregon State University, School of Mechanical, Industrial and Manufacturing Engineering, 204 Rogers Hall, Corvallis, OR 97331, United States.

Uranium-Molybdenum (U-Mo) low enriched uranium (LEU) fuels are a promising candidate for the replacement of high enriched uranium (HEU) fuels currently in use in a high power research and test reactors around the world. Contemporary U-Mo fuel sample preparation uses focused ion beam (FIB) methods for analysis of fission gas porosity. However, FIB possess several drawbacks, including reduced area of analysis, curtaining effects, and increased FIB operation time and cost. Vibratory polishing is a well understood method for preparing large sample surfaces with very high surface quality. In this research, fission gas porosity image analysis results are compared between samples prepared using vibratory polishing and FIB milling to assess the effectiveness of vibratory polishing for irradiated fuel sample preparation. Scanning electron microscopy (SEM) imaging was performed on sections of irradiated U-Mo fuel plates and the micrographs were analyzed using a fission gas pore identification and measurement script written in MatLab. Results showed that the vibratory polishing method is preferentially removing material around the edges of the pores, causing the pores to become larger and more rounded, leading to overestimation of the fission gas porosity size. Whereas, FIB preparation tends to underestimate due to poor micrograph quality and surface damage leading to inaccurate segmentations. Despite the aforementioned drawbacks, vibratory polishing remains a valid method for porosity analysis sample preparation, however, improvements should be made to reduce the preferential removal of material surrounding pores in order to minimize the error in the porosity measurements.
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http://dx.doi.org/10.1016/j.micron.2018.04.010DOI Listing
July 2018

Ground reaction forces during a drop vertical jump: Impact of external load training.

Hum Mov Sci 2018 Jun 24;59:12-19. Epub 2018 Mar 24.

Neuromechanics Laboratory, Department of Kinesiology, Mississippi State University, PO Box 6186, Mississippi State, MS 39762, USA.

External load training (ELT) is a supplemental training method used to potentially improve high intensity task performance. However, biomechanical parameters such as ground reaction forces (GRF), ground contact time, and time to peak GRF during a drop vertical jump (DVJ) following an ELT intervention have yet to be examined. Therefore, this study investigated the impact of ELT on certain biomechanical parameters of a DVJ task. Well-trained females stratified into two groups (ELT = 9, Control = 10) completed a DVJ from a 45.72 cm box onto a force platform at baseline, post-ELT, and post-detraining (DET). ELT consisted of wearing weight vests (WV) with 8% body mass for 32 h/week during daily living and 3 training sessions/week for 3 weeks. After ELT, a 3 week DET phase was completed. The control group replicated procedures without ELT intervention. The vertical, medial/lateral, and anterior/posterior components of the GRF were assessed during the initial contact, minimum force following initial contact, push-off, and second landing periods. Dependent variables were analyzed using a 2 (group) × 3 (time) mixed model ANOVA (p < .05). Significantly greater peak vertical GRF during the initial contact period was identified for the ELT group. Significant increases in the minimum vertical GRF following the initial contact period from baseline to post-ELT following the were observed for the ELT group, while significant increases in peak vertical GRF during the second landing period at post-ELT and post-DET in comparison to baseline was observed for both groups. The combination of greater vertical GRF during the initial contact period and the period following initial contact suggests that ELT may increase GRFs during a DVJ in comparison to routine training without a weighted vest.
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http://dx.doi.org/10.1016/j.humov.2018.03.011DOI Listing
June 2018

Current Perspectives in Imaging Modalities for the Assessment of Unruptured Intracranial Aneurysms: A Comparative Analysis and Review.

World Neurosurg 2018 May 31;113:280-292. Epub 2018 Jan 31.

Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA. Electronic address:

Background: Intracranial aneurysms (IAs) are pathologic dilatations of cerebral arteries. This systematic review summarizes and compares imaging techniques for assessing unruptured IAs (UIAs). This review also addresses their uses in different scopes of practice. Pathophysiologic mechanisms are reviewed to better understand the clinical usefulness of each imaging modality.

Methods: A literature review was performed using PubMed with these search terms: "intracranial aneurysm," "cerebral aneurysm," "magnetic resonance angiography (MRA)," computed tomography angiography (CTA)," "catheter angiography," "digital subtraction angiography," "molecular imaging," "ferumoxytol," and "myeloperoxidase". Only studies in English were cited.

Results: Since the development and improvement of noninvasive diagnostic imaging (computed tomography angiography and magnetic resonance angiography), many prospective studies and meta-analyses have compared these tests with gold standard digital subtraction angiography (DSA). Although computed tomography angiography and magnetic resonance angiography have lower detection rates for UIAs, they are vital in the treatment and follow-up of UIAs. The reduction in ionizing radiation and lack of endovascular instrumentation with these modalities provide benefits compared with DSA. Novel molecular imaging techniques to detect inflammation within the aneurysmal wall with the goal of stratifying risk based on level of inflammation are under investigation.

Conclusions: DSA remains the gold standard for preoperative planning and follow-up for patients with IA. Newer imaging modalities such as ferumoxytol-enhanced magnetic resonance imaging are emerging techniques that provide critical in vivo information about the inflammatory milieu within aneurysm walls. With further study, these techniques may provide aneurysm rupture risk and prediction models for individualized patient care.
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http://dx.doi.org/10.1016/j.wneu.2018.01.054DOI Listing
May 2018

Fibroblast growth factor receptor 1 amplification in laryngeal squamous cell carcinoma.

PLoS One 2018 19;13(1):e0186185. Epub 2018 Jan 19.

Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.

Fibroblast growth factor receptor 1 (FGFR1) has been noted to be amplified in a variety of squamous cell carcinomas (SCCa) of the head, neck, and lung and increased copy number (CN) is a predictor of poor outcomes. FGFR1 is a therapeutic target for lung SCCa and inhibition therapy is currently in clinical trials. Absolute quantification of FGFR1 from formalin fixed paraffin embedded (FFPE) tissue of laryngeal SCCa was examined in this retrospective study. A droplet digital polymerase chain reaction (ddPCR) was used for absolute quantitation of the FGFR1 gene CN. Of the 74 samples analyzed, FGFR1 CN analysis revealed 54% of samples had CN greater than 2 copies/cell (1.8-2.2 copies/cell), and 38% had CN values greater than 3. The mean and standard deviation FGFR1 CN was 4.17 ± 1.46 CN for African American patients (n = 41) and 3.78 ±1.85 CN for Caucasian patients (n = 31). Further, 60.9% of specimens from African Americans demonstrated increased FGFR1 CN compared to 48.4% of Caucasians. Two SCCA samples from Native American demonstrated increased FGFR1 CN (4.19 and 3.01 CN). The level of FGFR1 amplification did not correlate with tumor stage, lymph node staging, or metastasis. In this population, the proportion of patient samples with an FGFR1 amplification was three times higher than in reported for SCCA of the head and neck. Further, increased FGFR1 CN was observed in two racial groups not previously reported: African Americans and Native Americans. However, FGFR1 amplification is not prognostic in laryngeal squamous cell carcinomas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186185PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774678PMC
February 2018

Effects of 2% Dehydration on Lactate Concentration During Constant-Load Cycling.

J Strength Cond Res 2018 Jul;32(7):2066-2071

Department of Health and Fitness Management, Clayton State University, Morrow, Georgia.

Green, JM, Miller, B, Simpson, J, Dubroc, D, Keyes, A, Neal, K, Gann, J, and Andre, T. Effects of 2% dehydration on lactate concentration during constant-load cycling. J Strength Cond Res 32(7): 2066-2071, 2018-The lactate [La] threshold (LT) can predict endurance performance potential. Dehydration may alter LT. This study examined effects of dehydration on [La] response during constant-load cycling. Recreationally fit (V[Combining Dot Above]O2peak = 48.7 ± 5.2 ml·kg·min) male participants (n = 9) completed 2 × 40-minute constant-load cycling trials; euhydrated (HYD) and after previous evening passive (water bath) dehydration (2% body weight, DEH) (HYD and DEH counterbalanced). Lactate, heart rate (HR), 10-point Omni ratings of perceived exertion (RPE), and rectal temperature (Trec) were measured after warm-up (WU) and at 10, 20, 30, and 40 minutes. Before cycling, urine specific gravity (USG) was measured and participants estimated perceived recovery status (PRS). Urine specific gravity DEH (1.027 ± 0.004) was significantly greater than HYD (1.013 ± 0.007). After WU, [La] was significantly greater (all time points) for DEH (∼4.1 mmol·L) vs. HYD (∼3.5 mmol·L) with similar results for HR (DEH: ∼167, HYD: ∼158 b·min). For DEH, RPE was significantly greater (∼1 unit) at 20, 30, and 40 minutes, and Trec was significantly greater at 30 and 40 minutes (∼0.4° C). DEH (vs. HYD) also resulted in significantly different resting HR (93 ± 6, vs. 85 ± 7 b·min), significantly greater session RPE (7.7 ± 1.1 vs. 5.3 ± 1.1), and significantly lower subjective feelings of recovery (PRS = 6.4 ± 2.9, vs. 9.0 ± 1.5). Current results indicate systematic changes in [La] and associated physiological responses result from previous day dehydration. Hydration status should be a concern in paradigms where [La] assessment is used.
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http://dx.doi.org/10.1519/JSC.0000000000002293DOI Listing
July 2018

Cerebral venous sinus thrombosis after cranial surgery in children.

Childs Nerv Syst 2018 02 15;34(2):187-188. Epub 2017 Nov 15.

Department of Neurosurgery, University of Kentucky Hospital, 800 Rose Street, 40536, Lexington, USA.

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http://dx.doi.org/10.1007/s00381-017-3642-4DOI Listing
February 2018

Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage.

World Neurosurg 2018 Feb 31;110:e150-e159. Epub 2017 Oct 31.

Cerebrovascular Research Laboratory, Emory University School of Medicine, Atlanta, Georgia; Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Background: Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH.

Methods: We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically.

Results: PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days.

Conclusions: PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH.
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http://dx.doi.org/10.1016/j.wneu.2017.10.118DOI Listing
February 2018

Multispectral Imaging Analysis of Circulating Tumor Cells in Negatively Enriched Peripheral Blood Samples.

Methods Mol Biol 2017 ;1634:219-234

William G. Lowrie Department of Chemical and Biomolecular Engineering, Ohio State University, 151 W. Woodruff Ave., Columbus, OH, 43210, USA.

A variety of biomarkers are present on cells in peripheral blood of patients with a variety of disorders, including solid tumor malignancies. While rare, characterization of these cells for specific protein levels with the advanced technology proposed, will lead to future validation studies of blood samples as "liquid biopsies" for the evaluation of disease status and therapeutic response. While circulating tumor cells (CTCs) have been isolated in the blood samples of patients with solid tumors, the exact role of CTCs as clinically useful predictive markers is still debated. Current commercial technology has significant bias in that a positive selection technology is used that preassumes specific cell surface markers (such as EpCAM) are present on CTCs. However, CTCs with low EpCAM expression have been experimentally demonstrated to be more likely to be missed by this method. In contrast, this application uses a previously developed, technology that performs a purely negative enrichment methodology on peripheral blood, yielding highly enriched blood samples that contain CTCs as well as other, undefined cell types. The focus of this contribution is the use of multispectral imaging of epifluorescent, microscopic images of these enriched cells in order to help develop clinically relevant liquid biopsies from peripheral blood samples.
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http://dx.doi.org/10.1007/978-1-4939-7144-2_19DOI Listing
April 2018

Applications of a robotic stereotactic arm for pediatric epilepsy and neurooncology surgery.

J Neurosurg Pediatr 2017 Oct 4;20(4):364-370. Epub 2017 Aug 4.

Department of Neurosurgery, Washington University School of Medicine in St. Louis, Missouri.

OBJECTIVE The ROSA device is a robotic stereotactic arm that uses a laser system to register the patient's head or spine with MR or CT images. In this study, the authors analyze their experience with this system in pediatric neurosurgical applications and present selected cases that exemplify the usefulness of this system. METHODS The authors reviewed all cases that utilized the ROSA system at their institution. Patient demographics, pathology, complications, electrode placement, laser ablation, and biopsy accuracy were analyzed. Patient disposition and condition at follow-up were also analyzed. RESULTS Seventeen patients underwent 23 procedures using the ROSA system. A total of 87 electroencephalography electrodes were placed, with 13% deviating more than 3 mm from target. Six patients underwent stereotactic needle biopsy, and 9 underwent laser interstitial thermotherapy (LITT). One patient who underwent LITT required a subsequent craniotomy for tumor resection. Another patient experienced an asymptomatic extraaxial hematoma that spontaneously resolved. No patient suffered neurological complications during follow-up. Follow-up from the last procedure averaged 180 days in epilepsy patients and 309 days in oncology patients. CONCLUSIONS The precision, ease of use, and versatility of the ROSA system make it well suited for pediatric neurosurgical practice. Further work, including long-term analysis of results and cost-effectiveness, will help determine the utility of this system and if its applications can be expanded.
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http://dx.doi.org/10.3171/2017.5.PEDS1782DOI Listing
October 2017

Hydrocephalus presenting as idiopathic aqueductal stenosis with subsequent development of obstructive tumor: report of 2 cases demonstrating the importance of serial imaging.

J Neurosurg Pediatr 2017 Oct 4;20(4):329-333. Epub 2017 Aug 4.

Departments of 1 Neurological Surgery.

The authors describe 2 cases of triventricular hydrocephalus initially presenting as aqueductal stenosis that subsequently developed tumors of the pineal and tectal region. The first case resembled late-onset idiopathic aqueductal stenosis on serial imaging. Subsequent imaging revealed a new tumor in the pineal region causing mass effect on the midbrain. The second case presented in a more typical pattern of aqueductal stenosis during infancy. On delayed follow-up imaging, an enlarging tectal mass was discovered. In both cases hydrocephalus was successfully treated by cerebrospinal fluid diversion prior to tumor presentation. The differential diagnoses, diagnostic testing, and treatment course for these unusual cases are discussed. The importance of follow-up MRI in cases of idiopathic aqueductal stenosis is emphasized by these exemplar cases.
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http://dx.doi.org/10.3171/2017.5.PEDS1779DOI Listing
October 2017

External load training does not alter balance performance in well-trained women.

Sports Biomech 2018 Sep 21;17(3):336-349. Epub 2017 Jul 21.

a Department of Kinesiology , Mississippi State University , Mississippi State , MS , USA.

This study investigated the influence of external load training (ELT) on static and dynamic balance. Nineteen females stratified into two groups (ELT = 9, control = 10) completed three testing sessions over 6 weeks. The ELT group wore weighted vests (WV) of ~8% body mass for 32 h/week during daily living and three training sessions/week for 3 weeks. Following completion of ELT, a 3 week detraining (DET) phase was completed. Bilateral and unilateral static balance were assessed with eyes open and closed. Dynamic balance was assessed using the star excursion balance test (SEBT). Static and dynamic balance variables were analysed using a 2 (group) x 3 (time) between participants repeated measures ANOVA (p < 0.05). Results revealed significant reductions in average centre of pressure (COP) velocity in the control group on the non-dominant limb with eyes closed, and significantly greater reach distances in the ELT group on the SEBT for the posteromedial and medial directions on the dominant limb (p < 0.05). These findings suggest the ELT group did not significantly improve their balance in comparison to the control group. However, future research should further examine this unique, supplemental training method and the impact on balance performance.
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http://dx.doi.org/10.1080/14763141.2017.1341546DOI Listing
September 2018