MicroRNA Alterations in Chronic Traumatic Encephalopathy and Amyotrophic Lateral Sclerosis.

Repetitive head impacts (RHI) and traumatic brain injuries are risk factors for the neurodegenerative diseases chronic traumatic encephalopathy (CTE) and amyotrophic lateral sclerosis (ALS). ALS and CTE are distinct disorders, yet in some instances, share pathology, affect similar brain regions, and occur together. The pathways involved and biomarkers for diagnosis of both diseases are largely unknown. MicroRNAs (miRNAs) involved in gene regulation may be altered in neurodegeneration and be useful as stable biomarkers. Thus, we set out to determine associations between miRNA levels and disease state within the prefrontal cortex in a group of brain donors with CTE, ALS, CTE + ALS and controls. Of 47 miRNAs previously implicated in neurological disease and tested here, 28 (60%) were significantly different between pathology groups. Of these, 21 (75%) were upregulated in both ALS and CTE, including miRNAs involved in inflammatory, apoptotic, and cell growth/differentiation pathways. The most significant change occurred in miR-10b, which was significantly increased in ALS, but not CTE or CTE + ALS. Overall, we found patterns of miRNA expression that are common and unique to CTE and ALS and that suggest shared and distinct mechanisms of pathogenesis.

Utility of the ALSFRS-R for predicting ALS and comorbid disease neuropathology: The Veterans Affairs Biorepository Brain Bank.

INTRODUCTION/AIMS: The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) is commonly used to track ALS disease progression; however, there are gaps in the literature regarding the extent to which the ALSFRS-R relates to underlying central nervous system (CNS) pathology. The current study explored the association between ALSFRS-R (total and subdomain) scores and postmortem neuropathology (both ALS-specific and comorbid disease). METHODS: Within our sample of 93 military veterans with autopsy-confirmed ALS, we utilized hierarchical cluster analysis (HCA) to identify discrete profiles of motor dysfunction based on ALSFRS-R subdomain scores. We examined whether emergent clusters were associated with neuropathology. Separate analyses of variance and covariance with post-hoc comparisons were performed to examine relevant cluster differences. RESULTS: Analyses revealed significant correlations between ALSFRS-R total and subdomain scores with some, but not all, neuropathological variables. The HCA illustrated three groups: Cluster 1-predominantly diffuse functional impairment; Cluster 2-spared respiratory/bulbar and impaired motor function; and Cluster 3-spared bulbar and impaired respiratory, and fine and gross motor function. Individuals in Cluster 1 (and to a lesser degree, Cluster 3) exhibited greater accumulation of ALS-specific neuropathology and less comorbid neuropathology than those in Cluster 2. DISCUSSION: These results suggest that discrete patterns of motor dysfunction based on ALSFRS-R subdomain scores are related to postmortem neuropathology. Findings support use of ALSFRS-R subdomain scores to capture the heterogeneity of clinical presentation and disease progression in ALS, and may assist researchers in identifying endophenotypes for separate assessment in clinical trials.

Observation and Manipulation of a Phase Separated State in a Charge Density Wave Material.

The 1T polytype of TaS2 has been studied extensively as a strongly correlated system. As 1T-TaS2 is thinned toward the 2D limit, its phase diagram shows significant deviations from that of the bulk material. Optoelectronic maps of ultrathin 1T-TaS2 have indicated the presence of nonequilibrium charge density wave phases within the hysteresis region of the nearly commensurate (NC) to commensurate (C) transition. We perform scanning tunneling microscopy on exfoliated ultrathin flakes of 1T-TaS2 within the NC-C hysteresis window, finding evidence that the observed nonequilibrium phases consist of intertwined, irregularly shaped NC-like and C-like domains. After applying lateral electrical signals to the sample, we image changes in the geometric arrangement of the different regions. We use a phase separation model to explore the relationship between electronic inhomogeneity present in ultrathin 1T-TaS2 and its bulk resistivity. These results demonstrate the role of phase competition morphologies in determining the properties of 2D materials.

The Department of Veterans Affairs Gulf War Veterans' Illnesses Biorepository: Supporting Research on Gulf War Veterans' Illnesses.

AIMS: To introduce a resource supporting research on Gulf War illness (GWI) and related disorders, the Gulf War Veterans' Illnesses Biorepository (GWVIB). METHODS: Gulf War era veterans (GWVs) are recruited nationally and enrolled via telephone and email/postal mail. Enrolled veterans receive annual telephone and mail follow-up to collect health data until their passing. A postmortem neuropathological examination is performed, and fixed and frozen brain and spinal cord samples are banked to support research. Investigators studying GWI and related disorders may request tissue and data from the GWVIB. RESULTS: As of September 2021, 127 GWVs from 39 states were enrolled; 60 met the criteria for GWI, and 14 met the criteria for chronic multisymptom illness (CMI). Enrollees have been followed up to six years. Postmortem tissue recoveries were performed on 14 GWVs. The most commonly found neuropathologies included amyotrophic lateral sclerosis, chronic traumatic encephalopathy, and Lewy body disease. Tissue was of good quality with an average RNA integrity number of 5.8 (SD = 1.0) and ≥4.8 in all of the cases. DISCUSSION: The availability of health data and high-quality CNS tissue from this well-characterized GWV cohort will support research on GWI and related disorders affecting GWVs. Enrollment is ongoing.

Scale performance and composition in a small Amazonian armored catfish, Corydoras trilineatus.

The cory catfishes (Callichthyidae) are small, South American armored catfishes with a series of dermal scutes that run the length of the fish from posterior to the parieto-supraoccipital down to the caudal peduncle. In this study, we explore the anatomy and functional performance of the armored scutes in the three-striped cory catfish, Corydoras trilineatus. The lateral surface has a dorsal and a ventral row of scutes that interact at the horizontal septum. The scutes have little overlap with sequential posterior scutes (~33% overlap) and a deep ridge in the internal surface that connects to the underlying soft tissue. The internal surface of C. trilineatus scutes is stiffer than the external surface, contrary to the findings in a related species of cory catfish, C. aeneus, which documented a hypermineralized, enamel-like, non-collagenous, hyaloine layer along the external surface of the scute. Clearing and staining of C. trilineatus scutes revealed that the scutes have highly mineralized (~50% mineralization) regions embedded in between areas of low mineralization along the posterior margin. Puncture tests showed that posterior scutes were weaker than both anterior and middle scutes, and scutes attached to the body required 50% more energy to puncture than isolated scutes. Corydoras trilineatus has the strongest armor in areas critical for protecting vital organs and the external armored scute receives synergistic benefits from interactions to the soft underlying tissue, which combine to provide a tough protective armor that still allows for flexible mobility.

Neuropathological profile of long-duration amyotrophic lateral sclerosis in military Veterans.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Although ALS typically leads to death within 3 to 5 years after initial symptom onset, approximately 10% of patients with ALS live more than 10 years after symptom onset. We set out to determine similarities and differences in clinical presentation and neuropathology in persons with ALS with long vs. those with standard duration. Participants were United States military Veterans with a pathologically confirmed diagnosis of ALS (n = 179), dichotomized into standard duration (<10 years) and long-duration (≥10 years). The ALS Functional Rating Scale-Revised (ALSFRS-R) was administered at study entry and semi-annually thereafter until death. Microglial density was determined in a subset of participants. long-duration ALS occurred in 76 participants (42%) with a mean disease duration of 16.3 years (min/max = 10.1/42.2). Participants with long-duration ALS were younger at disease onset (P = 0.002), had a slower initial ALS symptom progression on the ALSFRS-R (P < 0.001) and took longer to diagnose (P < 0.002) than standard duration ALS. Pathologically, long-duration ALS was associated with less frequent TDP-43 pathology (P < 0.001). Upper motor neuron degeneration was similar; however, long-duration ALS participants had less severe lower motor neuron degeneration at death (P < 0.001). In addition, the density of microglia was decreased in the corticospinal tract (P = 0.017) and spinal cord anterior horn (P = 0.009) in long-duration ALS. Notably, many neuropathological markers of ALS were similar between the standard and long-duration groups and there was no difference in the frequency of known ALS genetic mutations. These findings suggest that the lower motor neuron system is relatively spared in long-duration ALS and that pathological progression is likely slowed by as yet unknown genetic and environmental modifiers.

Utility of pre-procedural CT and abdominal radiography before percutaneous radiologic gastrostomy placement.

PURPOSE: To evaluate the utility of pre-procedural CT and abdominal radiography before percutaneous radiologic gastrostomy tube placement. METHODS: A retrospective review of gastrostomy tube placements was conducted at a tertiary care radiology department. During the studied period, all percutaneous radiologic G-tube placements (PRG) at the institution required a pre-procedural abdominal CT. Whether the CT was interpreted to have an adequate window for PRG was recorded. The same patients with pre-procedural abdominal radiographs were also identified and retrospectively reviewed for the presence of satisfactory anatomy for PRG. Outcomes of tube placements were reviewed. RESULTS: 126 PRG requests were identified, all with abdominal CTs. 110 also had an abdominal radiograph. An adequate window for PRG was present in 83% of patients by CT and 73% by radiography. Of patients in whom it was attempted, 94% underwent successful PRG with a 7.4% minor complication rate. Of those refused for PRG based on CT, 9% had successful percutaneous endoscopic G-tube placement, resulting in a sensitivity of 98%. 97% of patients with satisfactory anatomy by radiograph underwent successful PRG. Of those with no window, 66% had a window by CT, and 94% in whom it was attempted had successful PRG placement. This resulted in a sensitivity of 77% for radiography. Concordance between CT and radiography was 73%. CONCLUSIONS: Pre-procedural CT interpretation is highly predictive of successful and uncomplicated PRG. Abdominal radiography also predicts successful PRG, but with a lower accuracy, limiting its utility as a pre-procedural exam.

Age at mating and male quality influence female patterns of reproductive investment and survival.

The trade-off between the allocation of resources toward somatic maintenance or reproduction is one of the fundamentals of life history theory and predicts that females invest in offspring at the expense of their longevity or vice versa. Mate quality may also affect life history trade-offs through mechanisms of sexual conflict; however, few studies have examined the interaction between mate quality and age at first mating in reproductive decisions. Using house crickets (Acheta domesticus), this study examines how survival and reproductive trade-offs change based on females' age at first reproduction and exposure to males of varying size. Females were exposed to either a large (presumably high-quality) or small male at an early (young), middle (intermediate), or advanced (old) age, and longevity and reproductive investment were subsequently tracked. Females mated at a young age had the largest number of eggs but the shortest total lifespans while females mated at older ages produced fewer eggs but had longer total lifespans. The trade-off between age at first mating and eggs laid appears to be mediated through higher egg-laying rates and shorter postmating lifespans in females mated later in life. Exposure to small males resulted in shorter lifespans and higher egg-laying rates for all females indicating that male manipulation of females, presumably through spermatophore contents, varies with male size in this species. Together, these data strongly support a trade-off between age at first reproduction and lifespan and support the role of sexual conflict in shaping patterns of reproduction.

Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive head impacts and has been associated with amyotrophic lateral sclerosis (ALS), a fatal, degenerative neuromuscular disorder. The Department of Veterans Affairs Biorepository Brain Bank (VABBB) is a tissue repository that collects antemortem disease progression data and postmortem central nervous system tissue from veterans with ALS. We set out to determine the frequency of co-morbid ALS and CTE in the VABBB cohort and to characterize the clinical, genetic, and pathological distinctions between participants with ALS only and those with both ALS and CTE (ALS+CTE). Of 155 participants, 9 (5.8%) had neuropathologically confirmed ALS+CTE. Participants with ALS+CTE were more likely to have a history of traumatic brain injury (p < 0.001), served during the first Persian Gulf War (p < 0.05), and to have more severe tau pathology within the frontal cortex and spinal cord (p < 0.05). The most common exposures to head impacts included contact sports (n = 5) and military service (n = 2). Clinically, participants with ALS+CTE were more likely to have bulbar onset ALS (p = 0.006), behavioral changes (p = 0.002), and/or mood changes (p < 0.001). Overall, compared with ALS in isolation, comorbid ALS+CTE is associated with a history of TBI and has a distinct clinical and pathological presentation.

Electromagnetic tracking of flexible robotic catheters enables "assisted navigation" and brings automation to endovascular navigation in an in vitro study.

OBJECTIVE: Combining three-dimensional (3D) catheter control with electromagnetic (EM) tracking-based navigation significantly reduced fluoroscopy time and improved robotic catheter movement quality in a previous in vitro pilot study. The aim of this study was to expound on previous results and to expand the value of EM tracking with a novel feature, assistednavigation, allowing automatic catheter orientation and semiautomatic vessel cannulation. METHODS: Eighteen users navigated a robotic catheter in an aortic aneurysm phantom using an EM guidewire and a modified 9F robotic catheter with EM sensors at the tip of both leader and sheath. All users cannulated two targets, the left renal artery and posterior gate, using four visualization modes: (1) Standard fluoroscopy (control). (2) 2D biplane fluoroscopy showing real-time virtual catheter localization and orientation from EM tracking. (3) 2D biplane fluoroscopy with novel EM assisted navigation allowing the user to define the target vessel. The robotic catheter orients itself automatically toward the target; the user then only needs to advance the guidewire following this predefined optimized path to catheterize the vessel. Then, while advancing the catheter over the wire, the assisted navigation automatically modifies catheter bending and rotation in order to ensure smooth progression, avoiding loss of wire access. (4) Virtual 3D representation of the phantom showing real-time virtual catheter localization and orientation. Standard fluoroscopy was always available; cannulation and fluoroscopy times were noted for every mode and target cannulation. Quality of catheter movement was assessed by measuring the number of submovements of the catheter using the 3D coordinates of the EM sensors. A t-test was used to compare the standard fluoroscopy mode against EM tracking modes. RESULTS: EM tracking significantly reduced the mean fluoroscopy time (P < .001) and the number of submovements (P < .02) for both cannulation tasks. For the posterior gate, mean cannulation time was also significantly reduced when using EM tracking (P < .001). The use of novel EM assisted navigation feature (mode 3) showed further reduced cannulation time for the posterior gate (P = .002) and improved quality of catheter movement for the left renal artery cannulation (P = .021). CONCLUSIONS: These results confirmed the findings of a prior study that highlighted the value of combining 3D robotic catheter control and 3D navigation to improve safety and efficiency of endovascular procedures. The novel EM assisted navigation feature augments the robotic master/slave concept with automated catheter orientation toward the target and shows promising results in reducing procedure time and improving catheter motion quality.

Contained Rupture of an Abdominal Aortic Aneurysm With Extensive Vertebral Body and Retroperitoneal Space Destruction.

Chronic contained rupture of an abdominal aortic aneurysm with vertebral body erosion most commonly presents with symptoms of low back pain. Although not well known, vertebral body erosion or destruction may be seen in up to 25% of patients with sealed or contained rupture of an abdominal aortic aneurysm. This appearance on cross-sectional imaging may mimic a malignant or infectious process. Although these cases can present a diagnostic challenge, published cases of chronic contained rupture of an abdominal aortic aneurysm with vertebral body erosion demonstrate clinical and imaging similarities that, when recognized, can assist in diagnosis.

Flexible robotics with electromagnetic tracking improves safety and efficiency during in vitro endovascular navigation.

OBJECTIVE: One limitation of the use of robotic catheters is the lack of real-time three-dimensional (3D) localization and position updating: they are still navigated based on two-dimensional (2D) X-ray fluoroscopic projection images. Our goal was to evaluate whether incorporating an electromagnetic (EM) sensor on a robotic catheter tip could improve endovascular navigation. METHODS: Six users were tasked to navigate using a robotic catheter with incorporated EM sensors in an aortic aneurysm phantom. All users cannulated two anatomic targets (left renal artery and posterior "gate") using four visualization modes: (1) standard fluoroscopy mode (control), (2) 2D fluoroscopy mode showing real-time virtual catheter orientation from EM tracking, (3) 3D model of the phantom with anteroposterior and endoluminal view, and (4) 3D model with anteroposterior and lateral view. Standard X-ray fluoroscopy was always available. Cannulation and fluoroscopy times were noted for every mode. 3D positions of the EM tip sensor were recorded at 4 Hz to establish kinematic metrics. RESULTS: The EM sensor-incorporated catheter navigated as expected according to all users. The success rate for cannulation was 100%. For the posterior gate target, mean cannulation times in minutes:seconds were 8:12, 4:19, 4:29, and 3:09, respectively, for modes 1, 2, 3 and 4 (P = .013), and mean fluoroscopy times were 274, 20, 29, and 2 seconds, respectively (P = .001). 3D path lengths, spectral arc length, root mean dimensionless jerk, and number of submovements were significantly improved when EM tracking was used (P < .05), showing higher quality of catheter movement with EM navigation. CONCLUSIONS: The EM tracked robotic catheter allowed better real-time 3D orientation, facilitating navigation, with a reduction in cannulation and fluoroscopy times and improvement of motion consistency and efficiency.

Direct Evidence of Solution-Mediated Superoxide Transport and Organic Radical Formation in Sodium-Oxygen Batteries.

Advanced large-scale electrochemical energy storage requires cost-effective battery systems with high energy densities. Aprotic sodium-oxygen (Na-O2) batteries offer advantages, being comprised of low-cost elements and possessing much lower charge overpotential and higher reversibility compared to their lithium-oxygen battery cousins. Although such differences have been explained by solution-mediated superoxide transport, the underlying nature of this mechanism is not fully understood. Water has been suggested to solubilize superoxide via formation of hydroperoxyl (HO2), but direct evidence of these HO2 radical species in cells has proven elusive. Here, we use ESR spectroscopy at 210 K to identify and quantify soluble HO2 radicals in the electrolyte-cold-trapped in situ to prolong their lifetime-in a Na-O2 cell. These investigations are coupled to parallel SEM studies that image crystalline sodium superoxide (NaO2) on the carbon cathode. The superoxide radicals were spin-trapped via reaction with 5,5-dimethyl-pyrroline N-oxide at different electrochemical stages, allowing monitoring of their production and consumption during cycling. Our results conclusively demonstrate that transport of superoxide from cathode to electrolyte leads to the nucleation and growth of NaO2, which follows classical mechanisms based on the variation of superoxide content in the electrolyte and its correlation with the crystallization of cubic NaO2. The changes in superoxide content upon charge show that charge proceeds through the reverse solution process. Furthermore, we identify the carbon-centered/oxygen-centered alkyl radicals arising from attack of these solubilized HO2 species on the diglyme solvent. This is the first direct evidence of such species, which are likely responsible for electrolyte degradation.

The influence of nonconscious processes on perceptions of downsizing and terminations.

Although social and cognitive psychologists have developed a large body of research on priming and other nonconscious processes, relatively little research has focused on how these issues influence organizationally relevant phenomena. The current research sought to partially fill this void by examining the influence of nonconscious processes on perceptions of organizational downsizing. In three studies, individuals were primed with traits of self-reliance or employer-reliance either supraliminally (Study 1) or subliminally (Studies 2 and 3). Studies 1 and 2 found that individuals primed with self-reliance had less negative views of downsizing. Experiment 3 found that those primed with self-reliance reported greater perceptions of fair treatment, respect for their boss, and decreased levels of anger in response to a termination scenario. Implications and future directions are discussed.

On-call resident outside study overreads: Our department's experience streamlining workflow and improving resident supervision while providing a new source of revenue.

Handling the interpretation of outside studies or "curbside" consults can be a daily problem for many radiology departments. In this article, we describe the efforts of a resident quality improvement project to create a more streamlined workflow for the interpretation of outside studies. The principle goal of this project was to ensure that at our teaching hospital, any outside study presented to a resident on call also received a final staff interpretation. An additional goal of this project was to use the digital tools available in our department to streamline the workflow for providing these outside interpretations. The result is an integrated workflow that allows for increased resident supervision as well as a potential new source of revenue in being able to generate billable interpretations.

QM and QM/MM studies of uranyl fluorides in the gas and aqueous phases and in the hydrophobic cavities of tetrabrachion.

The structural properties and electronic structures of pentacoordinated uranyl complexes belonging to the [UO(2)F(n)(H(2)O)(5-n)](2-n) series have been studied in the gas and aqueous phases using density functionals with relativistic pseudopotentials and all-electron basis sets in the gas-phase calculations in combination with COSMO in the aqueous phase. In addition, the conformational orientation and structural and electronic properties of [UO(2)F(5)](3-) in the hydrophobic cavities of the right-handed coiled-coil (RHCC) protein of tetrabrachion have been determined using the hybrid QM/MM method. Although there is good agreement between the available experimental geometrical parameters and the values obtained in the aqueous phase using pseudopotentials or all-electron basis sets, variation of the uranyl U═O bond with the number of fluoride ligands is only truly captured after the inclusion of five water molecules in the second coordination sphere around the molecules. The docking procedure used in this work shows that there are only two possible orientations of the uranyl group of [UO(2)F(5)](3-) embedded in the hydrophobic cavities of the RHCC protein. The two orientations are exclusively along the axes perpendicular to the protein axial channel with no possible orientation of the uranyl group along the axial channel because of both steric effects and interaction with the alkyl chain of the isoleucine residues pointing into the axial channel. In addition, the embedded complex is always positioned nearer to the isoleucine residues at the N-terminal ends of the hydrophobic cavities. Energy analysis, however, reveals that both conformations can only be observed in cavity 2, the largest hydrophobic cavity. The structural and electronic properties of the ligand embedded in this cavity are very similar to those of the gas-phase structure. A comparable study of [Pt(CN)(6)](2-) and the anticancer drug cisplatin, [PtCl(2)(NH(3))(2)], in cavity 2, revealed the existence of just two orientations for the former, similar to the uranyl complex, and multiple orientations for the latter.