Circuit-Wide Gene Network Analysis Reveals Sex-Specific Roles for Phosphodiesterase 1b in Cocaine Addiction.

Cocaine use disorder is a significant public health issue without an effective pharmacological treatment. Successful treatments are hindered in part by an incomplete understanding of the molecular mechanisms that underlie long-lasting maladaptive plasticity and addiction-like behaviors. Here, we leverage a large RNA sequencing dataset to generate gene coexpression networks across six interconnected regions of the brain's reward circuitry from mice that underwent saline or cocaine self-administration. We identify phosphodiesterase 1b (Pde1b), a Ca2+/calmodulin-dependent enzyme that increases cAMP and cGMP hydrolysis, as a central hub gene within a nucleus accumbens (NAc) gene module that was bioinformatically associated with addiction-like behavior. Chronic cocaine exposure increases Pde1b expression in NAc D2 medium spiny neurons (MSNs) in male but not female mice. Viral-mediated Pde1b overexpression in NAc reduces cocaine self-administration in female rats but increases seeking in both sexes. In female mice, overexpressing Pde1b in D1 MSNs attenuates the locomotor response to cocaine, with the opposite effect in D2 MSNs. Overexpressing Pde1b in D1/D2 MSNs had no effect on the locomotor response to cocaine in male mice. At the electrophysiological level, Pde1b overexpression reduces sEPSC frequency in D1 MSNs and regulates the excitability of NAc MSNs. Lastly, Pde1b overexpression significantly reduced the number of differentially expressed genes (DEGs) in NAc following chronic cocaine, with discordant effects on gene transcription between sexes. Together, we identify novel gene modules across the brain's reward circuitry associated with addiction-like behavior and explore the role of Pde1b in regulating the molecular, cellular, and behavioral responses to cocaine.

In vivo locus-specific editing of the neuroepigenome.

Studies over the past several decades have identified numerous epigenetic mechanisms associated with pathological states in psychiatric and neurological disease. Until recently, studies investigating chromatin-regulatory proteins, using overexpression or knockdown approaches, did not establish causal roles for epigenetic modifications at specific genes because these techniques typically affect hundreds or thousands of genomic loci. In this Review, we describe recent efforts in using locus-specific neuroepigenome editing in vivo to, for the first time, define causal relationships between a single chromatin modification at a specific gene in a defined cell population and downstream measures at the molecular, cellular, circuit and behavioural levels. We briefly introduce three epigenome-editing platforms: zinc-finger proteins, transcriptional activator-like effectors and clustered regularly interspaced short palindromic repeats (CRISPR). We then explore the development of in vivo neuroepigenome-editing tools and their applications to resolve epigenetic contributions to the pathophysiology of brain diseases. We also discuss technical considerations for in vivo neuroepigenome-editing experiments and ongoing innovations in the field, including new tools to investigate chromatin marks, manipulate chromatin topology and induce epigenetic modifications at multiple genes in the same cell. Lastly, we explore the potential clinical applications of in vivo neuroepigenome editing for treating brain pathology.

Dectin-3-targeted antifungal liposomes efficiently bind and kill diverse fungal pathogens.

DectiSomes are anti-infective drug-loaded liposomes targeted to pathogenic cells by pathogen receptors including the Dectins. We have previously used C-type lectin (CTL) pathogen receptors Dectin-1, Dectin-2, and DC-SIGN to target DectiSomes to the extracellular oligoglycans surrounding diverse pathogenic fungi and kill them. Dectin-3 (also known as MCL, CLEC4D) is a CTL pathogen receptor whose known cognate ligands are partly distinct from other CTLs. We expressed and purified a truncated Dectin-3 polypeptide (DEC3) comprised of its carbohydrate recognition domain and stalk region. We prepared amphotericin B (AmB)-loaded pegylated liposomes (AmB-LLs) and coated them with this isoform of Dectin-3 (DEC3-AmB-LLs), and we prepared control liposomes coated with bovine serum albumin (BSA-AmB-LLs). DEC3-AmB-LLs bound to the exopolysaccharide matrices of Candida albicans, Rhizopus delemar (formerly known as R. oryzae), and Cryptococcus neoformans from one to several orders of magnitude more strongly than untargeted AmB-LLs or BSA-AmB-LLs. The data from our quantitative fluorescent binding assays were standardized using a CellProfiler program, AreaPipe, that was developed for this purpose. Consistent with enhanced binding, DEC3-AmB-LLs inhibited and/or killed C. albicans and R. delemar more efficiently than control liposomes and significantly reduced the effective dose of AmB. In conclusion, Dectin-3 targeting has the potential to advance our goal of building pan-antifungal DectiSomes.

Nanotube Structure of AsPS4-xSex (x = 0, 1).

Single-wall nanotubes of isostructural AsPS4-xSex (x = 0, 1) are grown from solid-state reaction of stoichiometric amounts of the elements. The structure of AsPS4 was determined using single-crystal X-ray diffraction and refined in space group P1¯. The infinite, single-walled AsPS4 nanotubes have an outer diameter of ≈1.1 nm and are built of corner-sharing PS4 tetrahedra and AsS3 trigonal pyramids. Each nanotube is nearly hexagonal, but the ≈3.4 Å distance between S atoms on adjacent nanotubes allows them to easily slide past one another, resulting in the loss of long-range order. Substituting S with Se disrupted the crystallization of the nanotubes, resulting in amorphous products that precluded the determination of the structure for AsPS3Se. 31P solid-state NMR spectroscopy indicated a single unique tetrahedral P environment in AsPS4 and five different P environments all with different degrees of Se substitution in AsPS3Se. Optical absorption spectroscopy revealed an energy band gap of 2.7 to 2.4 eV for AsPS4 and AsPS3Se, respectively. Individual AsPS4 microfibers showed a bulk conductivity of 3.2 × 10-6 S/cm and a negative photoconductivity effect under the illumination of light (3.06 eV) in ambient conditions. Thus, intrinsic conductivity originates from hopping through empty trap states along the length of the AsPS4 nanotubes.

Common radiographic indices used to measure patellar height do not consistently identify patella alta and lack interchangeability between measurements.

PURPOSE: Abnormal patellar height has been identified as a source of aberrant mechanical functioning within the patellofemoral joint. The purpose of this study is to examine the statistical agreement among three commonly used classification methods: Blackburne-Peel (BPI), Caton-Deschamps (CDI) and Insall-Salvati (ISR), by evaluating (1) the rates of patella alta identification and (2) the ability for one index to predict another. METHODS: One hundred lateral knee radiographs were evaluated using BPI, CDI and ISR to classify each knee as patella normal, patella alta or patella baja. Linear regression analysis was performed to evaluate the relationship between each index. Conversion equations were then derived using the reported linear regression best-fit line, comparing each pair of indices. RESULTS: Patella alta was identified in 15 knees using BPI, 15 using CDI and 25 using ISR. A total of seven knees were classified as patella alta by all BPI, CDI and ISR. Statistical analysis revealed significant correlation (p ≤ 0.001) among BPI and CDI (R2 = 0.706), BPI and ISR (R2 = 0.328) and CDI and ISR (R2 = 0.288). Wilcoxon Signed-Rank test between the three indices revealed no significant difference between the means of converted and original indices. CONCLUSION: Despite their significant correlations and adequate reproducibility, variability between common patellar height indices render predictions and conversions between BPI, CDI and ISR inequivalent. Users of these indices must be aware of their incongruent properties when considering application to patients in the clinical setting. Furthermore, it remains unclear which patellar height measurement technique is the correct index to use in a given knee. This study highlights the need for further investigation to create a reliable and standardised method for identifying patella height. LEVEL OF EVIDENCE: Level IV.

Multimode Quasinormal Spectrum from a Perturbed Black Hole.

When two black holes merge, the late stage of gravitational wave emission is a superposition of exponentially damped sinusoids. According to the black hole no-hair theorem, this ringdown spectrum depends only on the mass and angular momentum of the final black hole. An observation of more than one ringdown mode can test this fundamental prediction of general relativity. Here, we provide strong observational evidence for a multimode black hole ringdown spectrum using the gravitational wave event GW190521, with a maximum Bayes factor of 56±1 (1σ uncertainty) preferring two fundamental modes over one. The dominant mode is the ℓ=m=2 harmonic, and the subdominant mode corresponds to the ℓ=m=3 harmonic. The amplitude of this mode relative to the dominant harmonic is estimated to be A_{330}/A_{220}=0.2_{-0.1}^{+0.2}. We estimate the redshifted mass and dimensionless spin of the final black hole as 330_{-40}^{+30}M_{⊙} and 0.86_{-0.11}^{+0.06}, respectively. We find that the final black hole is consistent with the no-hair theorem and constrain the fractional deviation from general relativity of the subdominant mode's frequency to be -0.01_{-0.09}^{+0.08}.

Key transcription factors mediating cocaine-induced plasticity in the nucleus accumbens.

Repeated cocaine use induces coordinated changes in gene expression that drive plasticity in the nucleus accumbens (NAc), an important component of the brain's reward circuitry, and promote the development of maladaptive, addiction-like behaviors. Studies on the molecular basis of cocaine action identify transcription factors, a class of proteins that bind to specific DNA sequences and regulate transcription, as critical mediators of this cocaine-induced plasticity. Early methods to identify and study transcription factors involved in addiction pathophysiology primarily relied on quantifying the expression of candidate genes in bulk brain tissue after chronic cocaine treatment, as well as conventional overexpression and knockdown techniques. More recently, advances in next generation sequencing, bioinformatics, cell-type-specific targeting, and locus-specific neuroepigenomic editing offer a more powerful, unbiased toolbox to identify the most important transcription factors that drive drug-induced plasticity and to causally define their downstream molecular mechanisms. Here, we synthesize the literature on transcription factors mediating cocaine action in the NAc, discuss the advancements and remaining limitations of current experimental approaches, and emphasize recent work leveraging bioinformatic tools and neuroepigenomic editing to study transcription factors involved in cocaine addiction.

Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity.

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+ Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD.

Neuroinflammation is initiated by activation of the brain's innate immune system in response to an inflammatory challenge. Insufficient control of neuroinflammation leads to enhanced or prolonged pathology in various neurological conditions including multiple sclerosis and Alzheimer's disease. Nicotinamide adenine dinucleotide (NAD+ ) plays critical roles in cellular energy metabolism and calcium homeostasis. Our previous study demonstrated that deletion of CD38, which consumes NAD+ , suppressed cuprizone-induced demyelination, neuroinflammation, and glial activation. However, it is still unknown whether CD38 directly affects neuroinflammation through regulating brain NAD+ level. In this study, we investigated the effect of CD38 deletion and inhibition and supplementation of NAD+ on lipopolysaccharide (LPS)-induced neuroinflammation in mice. Intracerebroventricular injection of LPS significantly increased CD38 expression especially in the hippocampus. Deletion of CD38 decreased LPS-induced inflammatory responses and glial activation. Pre-administration of apigenin, a flavonoid with CD38 inhibitory activity, or nicotinamide riboside (NR), an NAD+ precursor, increased NAD+ level, and significantly suppressed induction of cytokines and chemokines, glial activation and subsequent neurodegeneration after LPS administration. In cell culture, LPS-induced inflammatory responses were suppressed by treatment of primary astrocytes or microglia with apigenin, NAD+ , NR or 78c, the latter a specific CD38 inhibitor. Finally, all these compounds suppressed NF-κB signaling pathway in microglia. These results suggest that CD38-mediated neuroinflammation is linked to NAD+ consumption and that boosting NAD+ by CD38 inhibition and NR supplementation directly suppress neuroinflammation in the brain.

Assessing Flexural Strength Degradation of New Cubic Containing Zirconia Materials.

AIM: Newer zirconia materials may have greater strength degradation under cyclic fatigue with increased yttria and cubic content. The purpose of this study was to evaluate the flexural strength (FS) degradation of newer zirconia materials compared to more traditional tetragonal zirconia materials. MATERIALS AND METHODS: The following materials were tested: two 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) materials (Lava Plus, 3M ESPE; Katana ML, Kuraray), one 4 mol% partially stabilized zirconia (4Y-PSZ) material (Katana STML, Kuraray), two 5 mol% partially stabilized zirconia (5Y-PSZ) materials (Katana STML, Kuraray; Lava Esthetic, 3M ESPE), and one lithium disilicate material (IPS e.max CAD LT, Ivoclar Vivadent). Thirty beams were milled for each ceramic material with final dimensions of 4.0 × 1.3 × 18.0 mm after sintering or crystallization. Each specimen was placed on a 3-point bend test device on a universal testing machine (Instron, Norwood, MA). Flexural strength was determined on 10 beam specimens per group with a central load applied until fracture. Flexural fatigue strength was then measured on the remaining 20 beam specimens per group using the staircase method for 6,000 cycles at 2 Hz. Data were analyzed with one-way ANOVAs/Tukey post hoc tests (α = 0.05). RESULTS: A significant difference was found between groups (p < 0.001) per property. The 3Y-TZP zirconia materials had the greatest flexural and flexural fatigue strength. The cubic containing zirconia materials performed more moderately. The lithium disilicate material had the lowest strength values. The percent degradation in flexural fatigue strength of the 3Y-TZP zirconia materials was less than the 5Y-PSZ, Katana UTML, and the 4Y-PSZ, Katana STML, cubic containing materials, but similar to the 5Y-PSZ cubic containing material, Lava Esthetic. CONCLUSION: The amount of strength degradation was material dependent, with the 4Y-PSZ or 5Y-PSZ cubic containing zirconia materials demonstrating greater or similar strength degradation compared to the primarily tetragonal 3Y-TZP zirconia materials. CLINICAL SIGNIFICANCE: The differences in FS degradation between cubic containing materials and traditional zirconia materials could significantly impact the long-term success of these newer materials. Clinicians should be aware that these cubic containing materials may perform differently long-term than the very strong traditional 3Y-TZP materials and to follow manufacturer instructions on required material thickness and indications for use to prevent premature failure of the restoration.

Characterizing the local oxidation nanolithography on highly oriented pyrolytic graphite.

Here, we characterize the patterns obtained through local oxidation nanolithography (LON) on highly oriented pyrolytic graphite as the write bias, speed, and force were varied. Different types of patterns-bumps, cracked bumps, and trenches-were obtained and characterized using four shape descriptors-pattern width, pattern height, cut width and cut depth. With an increase in write bias the obtained pattern type varied from bumps to cracked bumps to trenches. The use of a bias above 7.25 V resulted in trenches with increased variability in shape descriptor values. Similarly, an increase in write speed demonstrated a transition from trenches to cracked bumps to bumps. An increase in write force from 75 to 150 nN showed a shift in the threshold voltage from 4.25 V to just under 3.75 V and formed cracked bumps instead of bumps. These findings help solve the mystery of why bumps were not reported at threshold voltages before 2008. We believe these findings will be enable uniform reproduction and report of LON pattern.

A comparison of sodium and hydrogen halides at the air-water interface.

New molecular models, parameterized to ab initio calculations, were developed to describe HBr and HI at the air-water interface. These were used to compare how the air-water interface influenced dissociation of NaX and HX, with X being Cl, Br, or I, and also their propensity for the interface. The polarizable multistate empirical valence bond method, which explicitly describes proton sharing, was used to model HX. Results showed that the air-water interface suppressed HX dissociation from a contact ion pair to a solvent separated to a greater degree than NaX dissociation. Furthermore, HX had a greater propensity for the interface than NaX, which was a consequence of the hydronium ion having a greatest interfacial activity of all species studied. As a consequence of this, the average configuration of dissociated HX, while in both contact ion and solvent separated ion pairs near the air-water interface, is with the dissociated hydrogen oriented more towards the air than the X atom.

Independent effects of step length and foot strike pattern on tibiofemoral joint forces during running.

The purpose of this study was to examine the effects of step length and foot strike pattern along with their interaction on tibiofemoral joint (TFJ) and medial compartment TFJ kinetics during running. Nineteen participants ran with a rear foot strike pattern at their preferred speed using a short (-10%), preferred, and long (+10%) step length. These step length conditions were then repeated using a forefoot strike pattern. Regardless of foot strike pattern, a 10% shorter step length resulted in decreased peak contact force, force impulse per step, force impulse per kilometre, and average loading rate at the TFJ and medial compartment, while a 10% increased step length had the opposite effects (all P < 0.05). A forefoot strike pattern significantly lowered TFJ and medial compartment TFJ average loading rates compared with a rear foot strike pattern (both <0.05) but did not change TFJ or medial compartment peak force, force impulse per step, or force impulse per km. The combination of a shorter step length and forefoot strike pattern produced the greatest reduction in peak medial compartment contact force (P < 0.05). Knowledge of these running modification effects may be relevant to the management or prevention of TFJ injury or pathology among runners.

Posterior Root Meniscal Tears: Preoperative, Intraoperative, and Postoperative Imaging for Transtibial Pullout Repair.

The menisci play an important biomechanical role in axial load distribution of the knees by means of hoop strength, which is contingent on intact circumferentially oriented collagen fibers and meniscal root attachments. Disruption of the meniscal root attachments leads to altered biomechanics, resulting in progressive cartilage loss, osteoarthritis, and subchondral edema, with the potential for development of a subchondral insufficiency fracture. Identification of meniscal root tears at magnetic resonance (MR) imaging is crucial because new arthroscopic surgical techniques (transtibial pullout repair) have been developed to repair meniscal root tears and preserve the tibiofemoral cartilage of the knee. An MR imaging classification of posterior medial meniscal root ligament lesions has been recently described that is dedicated to the posterior root of the medial meniscus. An arthroscopic classification of meniscal root tears has been described that can be applied to the anterior and posterior roots of both the medial meniscus and the lateral meniscus. This arthroscopic classification includes type 1, partial stable root tears; type 2, complete radial root tears; type 3, vertical longitudinal bucket-handle tears; type 4, complex oblique tears; and type 5, bone avulsion fractures of the root attachments. Knowledge of these classifications and the potential contraindications to meniscal root repair can aid the radiologist in the preoperative reporting of meniscal root tear types and the evaluation of the tibiofemoral cartilage. As more patients undergo arthroscopic repair of meniscal root tears, familiarity with the surgical technique and the postoperative radiographic and MR imaging appearance is important to adequately report the imaging findings. ©RSNA, 2016.

Institutional review of compliance with NCCN guidelines for breast cancer: lessons learned from real-time multidimensional synoptic reporting.

BACKGROUND: Variations exist in compliance with NCCN Guidelines. Prior reports of adherence to NCCN Guidelines contain limitations because of lack of contemporary review and incomplete listing of reasons for noncompliance. PURPOSE: To assess institutional compliance and assist national quality improvement strategies through identifying valid reasons for noncompliance. METHODS: Compliance with NCCN Guidelines was recorded prospectively using electronic synoptic templates for patients with newly diagnosed breast cancer treated at a single institution between January 2010 and December 2011. Compliance with NCCN Guidelines was recorded. The accuracy of real-time synoptic auditing methods compared with retrospective chart review and reasons for noncompliance was assessed. SAS 9.3 software was used for data analysis. RESULTS: Compliance with NCCN Guidelines among 395 patients was 94% for initial staging evaluation, 97% for surgery, 91% for chemotherapy, 89% for hormone therapy, 91% for radiation therapy, 85% for follow-up, and 100% for determination of estrogen receptor/progesterone receptor and HER2 status. Age, comorbidities, and stage influenced guideline compliance. The most common reasons for noncompliance were patient refusal, patient choice after shared decision-making, and overuse of testing. Synoptic templated reporting was accurate in 97% patients. CONCLUSIONS: High compliance with NCCN Guidelines was demonstrated. Reasons for noncompliance were identifiable. Compliance and nonadherence can be evaluated quickly with electronic synoptic reporting. This allows real-time action plans to address quality concerns and aids national risk adjustment for comparison and benchmarking.

Bony adaptation after expansion with light-to-moderate continuous forces.

INTRODUCTION: The purpose of this study was to evaluate the biologic response of dentoalveolar bone to archwire expansion with light-to-moderate continuous forces. METHODS: With a split-mouth experimental design, the maxillary right second premolars of 7 adult male dogs were expanded for 9 weeks using passive self-ligating brackets (Damon Q; Ormco, Orange, Calif) and 2 sequential archwires (0.016 × 0.022-in copper-nickel-titanium alloy, followed by 0.019 × 0.025-in copper-nickel-titanium alloy). Intraoral and radiographic measurements were made to evaluate tooth movements and tipping associated with expansion; archwire forces were measured using a force gauge. Microcomputed tomography was used to compare buccal bone height, total tooth height, total root height, and buccal bone thickness. Bone formation was evaluated histologically using tetracycline and calcein fluorescent labels and hematoxylin and eosin stains. RESULTS: Buccal expansion was produced by forces between 73 and 178 g. Compared with the control side, which showed no tooth movement, the experimental second premolars were expanded by 3.5 ± 0.9 mm and tipped by 15.8°. Buccal bone thickness was significantly thinner (about 0.2 mm) in the coronal aspects and significantly thicker (about 0.9 mm) in the apical aspects over the mesial roots. The tipping and expansion significantly (P <0.05) reduced buccal bone height (ie, caused dehiscences) at the mesial (about 2.9 mm) and distal (about 1.2 mm) roots. Bony apposition occurred on the trailing edges of tooth movement and on the leading edges of the second premolar apices. The axial microcomputed tomography slices indicated, and the bone histomorphometry and histology demonstrated, newly laid-down bone on the periosteal side of the buccal cortical surfaces. Ordered osteoblast aggregation was also evident on the periosteal surfaces of buccal bone, just cervical to the apparent center of rotation of the tooth. Tooth and root heights showed no significant differences between the experimental and control second premolars. CONCLUSIONS: Buccal expansion with light-to-moderate continuous forces produced 3.5 mm of tooth movement, uncontrolled tipping, and bone dehiscence, but no root resorption. Bone formation on the periosteal surfaces of cortical bone indicates that apposition is possible on the leading edge of tooth movements.

Comparing the effectiveness of robotic plantarflexion resistance and biofeedback between overground and treadmill walking.

Individuals with diminished walking performance caused by neuromuscular impairments often lack plantar flexion muscle activity. Robotic devices have been developed to address these issues and increase walking performance. While these devices have shown promise in their ability to increase musculature engagement of the lower limbs when used on a treadmill, most have not been developed or validated for overground walking and community use. Overground walking may limit the effectiveness of robotic devices due to differences in gait characteristics between walking terrains and reduced user engagement. The purpose of this study was to validate our multimodal robotic gait training system for overground walking in individuals with neuromuscular gait impairments. This untethered wearable robotic device can provide an ankle resistive torque proportional to the users' biological ankle torque. The device can also provide audio biofeedback based on users' plantar pressure intending to increase ankle power and muscle activity of the plantar flexors. Seven individuals with cerebral palsy participated. Participants walked overground and on a treadmill with our robotic gait training system in a single testing session. Results showed all seven participants to increase peak plantar flexor muscle activity, 10.3% on average, when walking with the gait trainer overground compared to treadmill. When compared to typical baseline overground walking, overground gait trainer use caused individuals to have slightly less knee joint excursion (3°) and moderately more ankle joint excursion (7°). This work supports our vision of using the wearable robotic device as a gait aid and rehabilitation tool in the home and community settings.

Altered Use of Context During Visual Perception in Psychotic Psychopathology: A Neurophysiological Investigation of Tuned and Untuned Suppression During Contrast Perception.

BACKGROUND AND HYPOTHESIS: The human visual system streamlines visual processing by suppressing responses to textures that are similar to their surrounding context. Surround suppression is weaker in individuals with schizophrenia (ISZ); this altered use of visuospatial context may relate to the characteristic visual distortions they experience. STUDY DESIGN: To understand atypical surround suppression in psychotic psychopathology, we investigated neurophysiological responses in ISZ, healthy controls (HC), individuals with bipolar disorder (IBP), and first-degree relatives (ISZR/IBPR). Participants performed a contrast judgment task on a circular target with annular surrounds, with concurrent electroencephalography. Orientation-independent (untuned) suppression was estimated from responses to central targets with orthogonal surrounds; the orientation-dependence of suppression was estimated by fitting an exponential function to the increase in suppression as surrounds became more aligned with the center. RESULTS: ISZ exhibited weakened untuned suppression coupled with enhanced orientation-dependence of suppression. The N1 visual evoked potential was associated with the orientation-dependence of suppression, with ISZ and ISZR (but not IBP or IBPR) showing enhanced orientation-dependence of the N1. Collapsed across orientation conditions, the N1 for ISZ lacked asymmetry toward the right hemisphere; this reduction in N1 asymmetry was associated with reduced untuned suppression, real-world perceptual anomalies, and psychotic psychopathology. The overall amplitude of the N1 was reduced in ISZ and IBP. CONCLUSIONS: Key measures of symptomatology for ISZ are associated with reductions in untuned suppression. Increased sensitivity for ISZ to the relative orientation of suppressive surrounds is reflected in the N1 VEP, which is commonly associated with higher-level visual functions such as allocation of spatial attention or scene segmentation.

Evidence for Superoxide-Initiated Oxidation of Aniline in Water by Pulsed, Atmospheric Pressure Plasma.

Plasma-driven solution electrochemistry (PDSE) uses plasma-generated reactive species to drive redox reactions in solution. Nonthermal, atmospheric pressure plasmas, when irradiating water, produce many redox species. While PDSE is a promising chemical tool, there is limited insight into the mechanisms of the reactions due to the variety of short-lived reagents produced. In this study, we use aniline as a model system for studying redox mechanisms of PDSE. We show that the plasma irradiation of aqueous aniline solutions drives the formation of polyaniline oligomer, which is suppressed under acidic starting conditions. The addition of (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO), a radical scavenger, decreases the formation of oligomer by 80%, and the addition of superoxide dismutase fully hinders oligomerization. These results lead us to conclude that the oligomerization of aniline by plasma irradiation is initiated by superoxide. This discovery provides novel insights into PDSE mechanisms and illustrates a potential method of harnessing superoxide for chemical reactions.

Correlation of Tibial Tubercle Overgrowth With Increased Posterior Tibial Slope: A Novel Radiographic Assessment.

Background: An elevated posterior tibial slope (PTS) is associated with an increased risk for anterior cruciate ligament and meniscal injury. Recent evidence suggests that the PTS is elevated in patients with Osgood-Schlatter disease. Purpose: To determine whether there is an association between objective measures of anterior tibial tubercle growth and PTS. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 100 radiographs were randomly selected from a sample of patients who had received a lateral knee radiograph that captured at least 15 cm of the tibia distal to the knee joint line at a single institution between December 2020 and March 2022. The PTS was measured, and tibial tubercle growth was quantified with 2 novel measurements. For these measurements, a line was drawn on the radiograph from the most anterosuperior point on the tibia to the point on the anterior cortex of the tibia 10 cm distal from the starting point. The tibial tubercle height (TTH) was measured as the perpendicular distance from this line to the most prominent portion of the anterior tibia. The anterior tibial tubercle angle (TTA) was measured as the angle between the endpoints of the line made previously and the most prominent portion of the tibial tubercle, with a more acute angle indicating a more prominent tibial tubercle. The relationship between TTA, TTH, and PTS was evaluated using a univariate linear regression model. Results: The mean patient age was 33.1 ± 14.1 years. The mean TTA was 158.6°± 4.7°, the mean TTH was 8.8 ± 2.0 mm, and the mean PTS was 9.7°± 2.6°. A significant correlation was found between PTS and TTA (r = -0.46; ß = -0.46; P < .001) as well as TTH (r = 0.43; ß = 0.43; P < .001). Conclusion: Objective measures of anterior tibial tubercle overgrowth correlated with an elevated PTS. Every 2.2° of anterior TTA deviation from the mean and every 2.3 mm in TTH deviation from the mean correlated with a 1° difference in the PTS. This suggests a link between the development of the tibial tubercle and PTS, and it potentially helps to explain why the PTS is elevated in certain patients.