Regulator of G protein signaling 6 (RGS6) in dopamine neurons promotes EtOH seeking, behavioral reward, and susceptibility to relapse.

Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). The neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Here, we developed novel RGS6fl/fl; DAT-iCreER mice to determine the role of RGS6 in DA neurons on EtOH consumption, reward, and relapse behaviors. We found that RGS6 is expressed in DA neurons in both human and mouse ventral tegmental area (VTA), and that RGS6 loss in mice upregulates DA transporter (DAT) expression in VTA DA neuron synaptic terminals. Remarkably, loss of RGS6 in DA neurons significantly reduced EtOH consumption, preference, and reward in a manner indistinguishable from that seen in RGS6-/- mice. Strikingly, RGS6 loss from DA neurons before or after EtOH behavioral reward is established significantly reduced (~ 50%) re-instatement of reward following extinguishment, demonstrating distinct roles of RGS6 in promoting reward and relapse susceptibility to EtOH. These studies identify DA neurons as the locus of RGS6 action in promoting EtOH consumption, preference, reward, and relapse. RGS6 is unique among R7 RGS proteins in promoting rather than suppressing behavioral responses to drugs of abuse and to modulate EtOH behavioral reward. This is a result of RGS6's pre-synaptic actions that we hypothesize promote VTA DA transmission by suppressing GPCR-Gαi/o-DAT signaling in VTA DA neurons. These studies identify RGS6 as a potential therapeutic target for behavioral reward and relapse to EtOH.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules. We found no differences between human females and males in interval timing response times (timing accuracy) or the coefficient of variance of response times (timing precision). Consistent with prior work, we also found no differences between female and male rodents in timing accuracy or precision. In female rodents, there was no difference in interval timing between estrus and diestrus cycle stages. Because dopamine powerfully affects interval timing, we also examined sex differences with drugs targeting dopaminergic receptors. In both female and male rodents, interval timing was delayed after administration of sulpiride (D2-receptor antagonist), quinpirole (D2-receptor agonist), and SCH-23390 (D1-receptor antagonist). By contrast, after administration of SKF-81297 (D1-receptor agonist), interval timing shifted earlier only in male rodents. These data illuminate sex similarities and differences in interval timing. Our results have relevance for rodent models of both cognitive function and brain disease by increasing representation in behavioral neuroscience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transabdominal motor evoked potential neuromonitoring of lumbosacral spine surgery.

BACKGROUND CONTEXT: Transcranial Motor Evoked Potentials (TcMEPs) can improve intraoperative detection of femoral plexus and nerve root injury during lumbosacral spine surgery. However, even under ideal conditions, TcMEPs are not completely free of false-positive alerts due to the immobilizing effect of general anesthetics, especially in the proximal musculature. The application of transcutaneous stimulation to activate ventral nerve roots directly at the level of the conus medularis (bypassing the brain and spinal cord) has emerged as a method to potentially monitor the motor component of the femoral plexus and lumbosacral nerves free from the blunting effects of general anesthesia. PURPOSE: To evaluate the reliability and efficacy of transabdominal motor evoked potentials (TaMEPs) compared to TcMEPs during lumbosacral spine procedures. DESIGN: We present the findings of a single-center 12-month retrospective experience of all lumbosacral spine surgeries utilizing multimodality intraoperative neuromonitoring (IONM) consisting of TcMEPs, TaMEPs, somatosensory evoked potentials (SSEPs), electromyography (EMG), and electroencephalography. PATIENT SAMPLE: Two hundred and twenty patients having one, or a combination of lumbosacral spine procedures, including anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), posterior spinal fusion (PSF), and/or transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Intraoperative neuromonitoring data was correlated to immediate post-operative neurologic examinations and chart review. METHODS: Baseline reliability, false positive rate, true positive rate, false negative rate, area under the curve at baseline and at alerts, and detection of pre-operative deficits of TcMEPs and TaMEPs were compared and analyzed for statistical significance. The relationship between transcutaneous stimulation voltage level and patient BMI was also examined. RESULTS: TaMEPs were significantly more reliable than TcMEPs in all muscles except abductor hallucis. Of the 27 false positive alerts, 24 were TcMEPs alone, and 3 were TaMEPs alone. Of the 19 true positives, none were detected by TcMEPs alone, 3 were detected by TaMEPs alone (TcMEPs were not present), and the remaining 16 true positives involved TaMEPs and TcMEPs. TaMEPs had a significantly larger area under the curve (AUC) at baseline than TcMEPs in all muscles except abductor hallucis. The percent decrease in TcMEP and TaMEP AUC during LLIF alerts was not significantly different. Both TcMEPs and TaMEPs reflected three pre-existing motor deficits. Patient BMI and TaMEP stimulation intensity were found to be moderately positively correlated. CONCLUSIONS: These findings demonstrate the high reliability and predictability of TaMEPs and the potential added value when TaMEPs are incorporated into multimodality IONM during lumbosacral spine surgery.

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

BACKGROUND: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD. OBJECTIVE: To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn. METHODS: We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions. RESULTS: We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration. CONCLUSIONS: This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.

Complementary cognitive roles for D2-MSNs and D1-MSNs in interval timing.

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds, which involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs exhibited opposing dynamics over temporal intervals as quantified by principal component analyses and trial-by-trial generalized linear models. MSN recordings helped construct and constrain a four-parameter drift-diffusion computational model. This model predicted that disrupting either D2-MSN or D1-MSNs would increase interval timing response times and alter MSN firing. In line with this prediction, we found that optogenetic inhibition or pharmacological disruption of either D2-MSNs or D1-MSNs increased response times. Pharmacologically disrupting D2-MSNs or D1-MSNs also increased response times, shifted MSN dynamics, and degraded trial-by-trial temporal decoding. Together, our findings demonstrate that D2-MSNs and D1-MSNs make complementary contributions to interval timing despite opposing dynamics, implying that striatal direct and indirect pathways work together to shape temporal control of action. These data provide novel insight into basal ganglia cognitive operations beyond movement and have implications for a broad range of human striatal diseases and for therapies targeting striatal pathways.

Regulator of G protein signaling 6 (RGS6) in ventral tegmental area (VTA) dopamine neurons promotes EtOH seeking, behavioral reward and susceptibility to relapse.

Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). EtOH is the most abused substance worldwide with chronic consumption often leading to the development of dependence and abuse. Unfortunately, the neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Here, we developed novel RGS6 fl/fl ; DAT-iCreER mice to determine the role of RGS6 in VTA DA neurons on EtOH consumption and reward behaviors. We found that RGS6 is expressed in DA neurons in both human and mouse VTA, and that RGS6 loss in mice upregulates DA transporter (DAT) expression in VTA DA neuron synaptic terminals. Remarkably, loss of RGS6 in VTA DA neurons significantly reduced EtOH consumption, preference, and reward in a manner indistinguishable from that seen in RGS6 -/- mice. Strikingly, RGS6 loss from VTA DA neurons before or after EtOH behavioral reward is established significantly reduced (∼50%) re-instatement of reward following extinguishment, demonstrating distinct roles of RGS6 in promoting reward and relapse susceptibility to EtOH. These studies illuminate a critical role of RGS6 in the mesolimbic circuit in promoting EtOH seeking, reward, and reinstatement. We propose that RGS6 functions to promote DA transmission through its function as a negative modulator of GPCR-Gα i/o -DAT signaling in VTA DA neurons. These studies identify RGS6 as a potential therapeutic target for behavioral reward and relapse to EtOH.

Sublaminar Band Fixation Provides Excellent Anchors for MAGEC Rod Distraction Systems.

MAGEC rods (NuVasive) provide distraction growth in early-onset scoliosis. Pedicle screw use with MAGEC rods can lead to anchor failure. Sublaminar bands offer superior fixation points for the MAGEC system while preserving pedicles and facets, avoiding spinal cord injury, and eliminating the need for fluoroscopy. Sublaminar bands can be safely used up to cervical vertebra four (C4), substantially decreasing the risk of complications such as anchor pull-out, rod breakage, and proximal junctional kyphosis that typically occurs with pedicle screws and hooks. This case demonstrates the viable option of sublaminar band fixation as an anchor system for MAGEC rods. This is a retrospective case review of one patient with early-onset scoliosis who underwent multiple osteotomies, spinal cord decompression, and placement of MAGEC rods with sublaminar bands. The patient had successful distraction procedures conducted routinely throughout a 44-month period with no associated implant complications or neurologic sequelae during that period. The patient had achieved maximal distraction with the implanted rods and thereafter underwent removal of the MAGEC rods and replacement implantation with longer MAGEC rods. The purpose of this case review was to demonstrate the superior fixation results provided with sublaminar band fixation for MAGEC rod distraction systems.

Signaling and meaning in organizational analytics: coping with Goodhart's Law in an era of digitization and datafication.

The future of work will be measured. The increasing and widespread adoption of analytics, the use of digital inputs and outputs to inform organizational decision making, makes the communication of data central to organizing. This article applies and extends signaling theory to provide a framework for the study of analytics as communication. We report three cases that offer examples of dubious, selective, and ambiguous signaling in the activities of workers seeking to shape the meaning of data within the practice of analytics. The analysis casts the future of work as a game of strategic moves between organizations, seeking to measure behaviors and quantify the performance of work, and workers, altering their behavioral signaling to meet situated goals. The framework developed offers a guide for future examinations of the asymmetric relationship between management and workers as organizations adopt metrics to monitor and evaluate work.

Testing Multiple Methods to Effectively Promote Use of a Knowledge Portal to Health Policy Makers: Quasi-Experimental Evaluation.

BACKGROUND: Health policy makers and advocates increasingly utilize online resources for policy-relevant knowledge. Knowledge brokering is one potential mechanism to encourage the use of research evidence in policy making, but the mechanisms of knowledge brokerage in online spaces are understudied. This work looks at knowledge brokerage through the launch of Project ASPEN, an online knowledge portal developed in response to a New Jersey legislative act that established a pilot program for adolescent depression screening for young adults in grades 7-12. OBJECTIVE: This study compares the ability to drive policy brief downloads by policy makers and advocates from the Project ASPEN knowledge portal using a variety of online methods to promote the knowledge portal. METHODS: The knowledge portal was launched on February 1, 2022, and a Google Ad campaign was run between February 27, 2022, and March 26, 2022. Subsequently, a targeted social media campaign, an email campaign, and tailored research presentations were used to promote the website. Promotional activities ended on May 31, 2022. Website analytics were used to track a variety of actions including new users coming to the website, page views, and policy brief downloads. Statistical analysis was used to assess the efficacy of different approaches. RESULTS: The campaign generated 2837 unique user visits to the knowledge portal and 4713 page views. In addition, the campaign generated 6.5 policy web page views/day and 0.7 policy brief downloads/day compared with 1.8 views/day and 0.5 downloads/day in the month following the campaign. The rate of policy brief page view conversions was significantly higher for Google Ads compared with other channels such as email (16.0 vs 5.4; P<.001) and tailored research presentations (16.0 vs 0.8; P<.001). The download conversion rate for Google Ads was significantly higher compared with social media (1.2 vs 0.1; P<.001) and knowledge brokering activities (1.2 vs 0.2; P<.001). By contrast, the download conversion rate for the email campaign was significantly higher than that for social media (1.0 vs 0.1; P<.001) and tailored research presentations (1.0 vs 0.2; P<.001). While Google Ads for this campaign cost an average of US $2.09 per click, the cost per conversion was US $11 per conversion to drive targeted policy web page views and US $147 per conversion to drive policy brief downloads. While other approaches drove less traffic, those approaches were more targeted and cost-effective. CONCLUSIONS: Four tactics were tested to drive user engagement with policy briefs on the Project ASPEN knowledge portal. Google Ads was shown to be effective in driving a high volume of policy web page views but was ineffective in terms of relative costs. More targeted approaches such as email campaigns and tailored research presentations given to policy makers and advocates to promote the use of research evidence on the knowledge portal website are likely to be more effective when balancing goals and cost-effectiveness.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules. We found no differences between human females and males in interval timing response times (timing accuracy) or the coefficient of variance of response times (timing precision). Consistent with prior work, we also found no differences between female and male rodents in timing accuracy or precision. In female rodents, there was no difference in interval timing between estrus and diestrus cycle stages. Because dopamine powerfully affects interval timing, we also examined sex differences with drugs targeting dopaminergic receptors. In both female and male rodents, interval timing was delayed after administration of sulpiride (D2-receptor antagonist), quinpirole (D2-receptor agonist), and SCH-23390 (D1-receptor antagonist). By contrast, after administration of SKF-81297 (D1-receptor agonist), interval timing shifted earlier only in male rodents. These data illuminate sex similarities and differences in interval timing. Our results have relevance for rodent models of both cognitive function and brain disease by increasing represenation in behavioral neuroscience.

Digital Nerve Injury: Assessment and Treatment.

Undertreated digital nerve injuries may result in sensory deficits and pain. Early recognition and treatment will optimize outcomes, and providers should maintain a high index of suspicion when assessing patients with open wounds. Acute, sharp lacerations may be amenable to direct repair while avulsion injuries or delayed repairs require adequate resection and bridging with nerve autograft, processed nerve allograft, or conduits. Conduits are most appropriate for gaps less than 15 mm, and processed nerve allografts have demonstrated reliable outcomes across longer gaps.

Glycolysis-enhancing α1-adrenergic antagonists modify cognitive symptoms related to Parkinson's disease.

Terazosin is an α1-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson's disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α1-adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD.

Hepatitis B in Heart Transplant Donors and Recipients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Expanding the heart donor pool to include patients with hepatitis B virus (HBV) could help ameliorate the organ shortage in heart transplantation. We performed a systematic review and meta-analysis to evaluate the management and recipient outcomes of D+/R- and D-/R+ heart transplants. METHODS: An electronic search was performed to identify all relevant studies published on heart transplants involving HBV+ donors and/or HBV+ recipients. A comparison was performed between two groups where heart transplants were performed a) D+/R- (n = 98) versus b) D-/R+ (n = 65). RESULTS: Overall, 13 studies were selected, comprising 163 patients. Mean patient age was 55 y (95% CI: 39, 78) and 79% (69, 86) were male. Active post-transplant HBV infection requiring antiviral treatment occurred in 11% (1, 69) of D+/R- recipients and 33% (9, 71) of D-/R+ recipients. Post-transplant antiviral therapy was given to 80% (6, 100) of D+/R- recipients compared to 72% (42, 90) of D-/R+ recipients (P = 0.84). Hepatitis-related mortality was observed in no D+/R- recipients and 7% (2, 27) of D-/R+ recipients. Survival 1-y post-transplant was comparable between both groups at 83% (83, 92) and 81% (61, 92) for D+/R- and D-/R+ transplants, respectively. CONCLUSIONS: Our review found that HBV D+/R- heart transplantation was associated with fewer active hepatitis infections and lower hepatitis-related mortality than D-/R+ transplantation, with comparable survival at 1 y. Additional studies utilizing HBV nucleic acid testing (NAT) to compare outcomes with HBsAg+ and anti-HBc+ donors are crucial to reach more definitive conclusions about the risk of donor-derived infections in this context.

Alpha-synuclein pre-formed fibrils injected into prefrontal cortex primarily spread to cortical and subcortical structures and lead to isolated behavioral symptoms.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD. To investigate the consequences of α-syn pathology in the cortex, we injected human α-syn pre-formed fibrils into the PFC of wildtype mice. We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; 3) increased open field exploration; and 4) did not affect susceptibility to an inflammatory challenge. This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.

Infection following CF-LVAD exchange for non-infectious indications: A systematic review and meta-analysis.

INTRODUCTION: Patients on continuous flow left ventricular assist devices (CF-LVADs) often require CF-LVAD exchange. The purpose of this study was to investigate the incidence of infection following CF-LVAD exchange performed for non-infectious indications. METHODS: An electronic literature search was performed to identify all studies of patients undergoing CF-LVAD exchange for pump thrombosis or device malfunction. Of 2,698 articles identified, 6 studies with 81 total patients met the inclusion criteria. Cohort-level data were pooled for meta-analysis. RESULTS: Mean patient age was 60 years (95% CI: 41-78), and 74% were male (95% CI: 61-84). Pump thrombosis was the most common indication for exchange in 70% of patients (95% CI: 47-86). Other indications were driveline fracture and electrical malfunction in 21% (95% CI: 5-56) and 12% (95% CI: 4-33) of patients, respectively. Prior to exchange, 95% of patients were on HeartMate II (HM2) LVADs (95% CI: 86-98) and average duration of support for these patients was 27.1 months (95% CI: 9.3-44.8). The majority were placed on a HM2 following exchange (88% (95% CI: 45-98)) versus HM3 (12% (95% CI: 2-55)). Follow-up was an average of 16.4 months (95% CI: 6.8-26.0). Following exchange, 16 of 81 patients developed infection, with pooled mean incidence of 24% (95% CI: 14-38). 30-day mortality was 14% (95% CI: 7-26). Survival at follow-up was 65% (95% CI: 52-76). CONCLUSIONS: Infection following CF-LVAD exchange can occur at rates higher than those observed with primary implantation; therefore, effective strategies need to implemented early and consistently to help lower infections rates and help improve outcomes following exchange.

Continuous-flow left ventricular assist devices associated survival awaiting heart and heart-kidney transplant.

BACKGROUND: Improvement in continuous-flow left ventricular assist device (CF-LVAD) technology has translated to better outcomes for patients on CF-LVAD support as a bridge-to-transplant. However, data are lacking regarding the subset of CF-LVAD patients with renal failure awaiting simultaneous heart-kidney transplant (HKTx). We sought to better understand the characteristics and outcomes of patients in this group. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify adult patients listed for heart transplant (HTx) or HKTx from January 1, 2009 to March 31, 2017. Patients were followed from time on waitlist to either removal from waitlist or transplantation. Demographic and clinical data for HTx and HKTx patients were assessed. Kaplan-Meier analysis assessed waitlist and post-transplant survival. For waitlisted patients, both death and removal from the waitlist due to deteriorating medical condition were considered events. RESULTS: Overall, 26 638 patients registered for transplant were analyzed. 25 111 (94%) were listed for HTx, and 1527 (6%) for HKTx. 7683 (29%) patients listed for HTx had CF-LVAD support. For those listed for HKTx, 441 (28%) underwent dialysis alone, 256 (17%) had CF-LVAD support alone, and 85 (6%) were treated with both CF-LVAD and dialysis. 15 567 (58%) underwent HTx, and 621 (2%) underwent HKTx. In these groups, post-transplant survival was similar (p = 0.06). Patients listed for HKTx treated with both dialysis and CF-LVAD had significantly worse waitlist survival compared to HKTx recipients (p < 0.001). CONCLUSION: Post-transplant survival is comparable between HTx and HKTx, and early survival is similar between HTx patients and those listed for HTx with CF-LVAD support. However, outcomes on the waitlist for HKTx in CF-LVAD patients on dialysis is significantly worse compared to HKTx recipients. This highlights the need to better account for this patient population when allocating organs.

Mice expressing P301S mutant human tau have deficits in interval timing.

Interval timing is a key executive process that involves estimating the duration of an interval over several seconds or minutes. Patients with Alzheimer's disease (AD) have deficits in interval timing. Since temporal control of action is highly conserved across mammalian species, studying interval timing tasks in animal AD models may be relevant to human disease. Amyloid plaques and tau neurofibrillary tangles are hallmark features of AD. While rodent models of amyloid pathology are known to have interval timing impairments, to our knowledge, interval timing has not been studied in models of tauopathy. Here, we evaluate interval timing performance of P301S transgenic mice, a widely studied model of tauopathy that overexpresses human tau with the P301S mutation. We employed an interval timing task and found that P301S mice consistently underestimated temporal intervals compared to wild-type controls, responding early in anticipation of the target interval. Our study indicating timing deficits in a mouse tauopathy model could have relevance to human tauopathies such as AD.

COVID-19 pandemic restrictions unmasks dangers of frequent injury mechanisms for common surgically treated pediatric fractures.

Purpose: This study examined the volume and characteristics of common surgically treated fractures in children during the COVID-19 pandemic. The worldwide spread of COVID-19 affected the society in numerous ways. Social distancing led to changes in the types of activities performed by individuals, including children. Physicians saw a shift in orthopedic trauma volume and distribution. We predicted that with the change in activities children participated in, the number or type of injuries sustained would change as well. Methods: A retrospective review was performed of children who sustained a surgically treated fracture of the forearm, supracondylar humerus, femur, or any open fracture during the COVID-19 pandemic compared to the previous 2 years (pre-pandemic). Patient demographics, insurance status, and mechanism of injury were recorded. Statistical analysis was performed. Results: Review of the medical records identified 791 children. The number of fractures decreased from an average of 295 per year pre-pandemic to 201 during the pandemic (p = 0.09). During the pandemic, there was a decrease in injuries resulting from a fall from the monkey bars for supracondylar humerus (21.2% to 8.2%, p < 0.01) and for forearm fractures (15.5% to 4.3%, p = 0.04). In contrast, the frequencies of falls from a skateboard, hoverboard, scooter, or bicycle and falls from household furniture increased during the pandemic. Conclusion: The observed decrease in monkey bar-related injuries provides further evidence as to the dangers of this piece of playground equipment in contributing to upper-extremity fractures in children. Level of evidence: Level III: Prognostic and Epidemiological.

Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1 receptors, and working memory.

Dopamine in the prefrontal cortex can be disrupted in human disorders that affect cognitive function such as Parkinson's disease (PD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia. Dopamine has a powerful effect on prefrontal circuits via the D1-type dopamine receptor (D1DR). It has been proposed that prefrontal dopamine has "inverted U-shaped" dynamics, with optimal dopamine and D1DR signaling required for peak cognitive function. However, the quantitative relationship between prefrontal dopamine and cognitive function is not clear. Here, we conducted a meta-analysis of published manipulations of prefrontal dopamine and the effects on working memory, a high-level executive function in humans, primates, and rodents that involves maintaining and manipulating information over seconds to minutes. We reviewed 646 articles and found that 75 studies met criteria for inclusion. Our quantification of effect sizes for dopamine, D1DRs, and behavior revealed a negative quadratic slope. This is consistent with the proposed inverted U-shape of prefrontal dopamine and D1DRs and working memory performance, explaining 10% of the variance. Of note, the inverted quadratic fit was much stronger for prefrontal D1DRs alone, explaining 26% of the variance, compared to prefrontal dopamine alone, explaining 10% of the variance. Taken together, these data, derived from a variety of manipulations and systems, demonstrate that optimal prefrontal dopamine signaling is linked with higher cognitive function. Our results provide insight into the fundamental dynamics of prefrontal dopamine, which could be useful for pharmacological interventions targeting prefrontal dopaminergic circuits, and into the pathophysiology of human brain disease. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comparison of Using Intraoperative Computed Tomography-Based 3-Dimensional Navigation and Fluoroscopy in Anterior Cervical Diskectomy and Fusion for Cervical Spondylosis.

OBJECTIVE: Anterior cervical diskectomy and fusion (ACDF) is a highly successful procedure to treat spinal cord or nerve root compression; however, complications can still occur. With advancements in imaging, 3-dimensional (3D) reconstruction allows real-time instrument tracking in a surgical field relative to the patient's anatomy. Here, we compare plate positioning and short-term outcomes when using 3D navigation to fluoroscopy in ACDF for degenerative spine disease. METHODS: All ACDFs for cervical spondylosis performed by 6 surgeons at a single center between 2010 and 2018 were included. ACDFs were divided into those performed using 3D navigation or fluoroscopy. Records were assessed for patient demographics, American Society of Anesthesiology score, number of operated interspaces, operative time, length of stay, perioperative complications, and 90-day readmissions. Postoperative images were reviewed for lateral and angular plate deviations. RESULTS: A total of 193 ACDFs performed with 3D navigation and 728 performed with fluoroscopy were included. After controlling for demographics and surgical characteristics, using 3D navigation was associated with less lateral plate deviation (P = 0.048) and longer operative times per interspace (P < 0.001) but was not associated with angular plate deviation (P = 0.724), length of stay (P = 0.393), perioperative complications (P = 0.844), and 90-day readmissions (P = 0.539). CONCLUSIONS: Using 3D navigation in ACDF for degenerative disease is associated with slightly more midline plate positioning and comparable short-term outcomes as using fluoroscopy and can be a suitable alternative. Advantages of using this technology, such as improved visualization of anatomy, should be weighed against disadvantages, such as increased operative time, on a per-patient basis.