Invasive Implanted Hemodynamic Monitoring in Patients With Complex Congenital Heart Disease: State-of-the-Art Review.

As the number of patients with congenital heart disease (CHD) continues to increase, the burden of heart failure (HF) in this population requires innovative strategies to individualize management. Given the success of implanted invasive hemodynamic monitoring (IHM) with the CardioMEMS HF system in adults with acquired HF, this is often suggested for use in patients with CHD, though published data are limited to case reports and case series. Therefore, this review summarizes the available published reports on the use of IHM in patients with complex CHD, describes novel applications, and highlights future directions for study. In patients with CHD, IHM has been used across the lifespan, from age 3 years to adulthood, with minimal device-related complications reported. IHM uses include (1) prevention of HF hospitalizations; (2) reassessment of hemodynamics after titration of medical therapy without repeated cardiac catheterization; (3) serial monitoring of at-risk patients for pulmonary hypertension to optimize timing of heart transplant referral; (4) and hemodynamic assessment with exercise (5) or after ventricular assist device placement. IHM has the potential to reduce the number of cardiac catheterizations in anatomically complex patients and, in patients with Fontan circulation, IHM pressures may have prognostic implications. In conclusion, though further studies are needed, as patients with CHD age and HF are more prevalent, this tool may assist CHD physicians in caring for this complex patient population.

Humeral Condylar Fractures in French Bulldogs: Prevalence of Contralateral Intracondylar Fissure, Treatment, and Outcome.

OBJECTIVE: The aim of this study was to report (1) the prevalence of contralateral humeral intracondylar GAP/HIF (HIF) in French Bulldogs with humeral condylar fractures (HCF) and (2) treatment and short- and long-term outcome in French Bulldogs with HCF. MATERIALS AND METHODS: Medical records of French Bulldogs treated surgically for HCF between January 2011 and November 2022 were reviewed. Perioperative imaging, surgical technique, complications, and long-term outcome were assessed. RESULTS: Eighty-nine dogs with HCF were included and 36/89 were diagnosed with HIF. Surgical repair was performed in all HCF and a prophylactic transcondylar screw was placed in 20/36 HIF. For prophylactic transcondylar screw placement, two dogs required immediate revision surgery. Complications occurred in 12/89 HCF, and there were major complications in 6/89 HCF. Long-term outcome evaluated by owner questionnaire (n = 27) was rated as being excellent in 18/27 dogs, good in 8/27 dogs, and fair in 1/27 dogs. CLINICAL SIGNIFICANCE: Forty percent of French Bulldogs with HCF had a contralateral HIF. HIF as a cause of HCF should be considered in the French Bulldog, and a computed tomography (CT) scan of both elbows may be advisable prior to HCF repair. The complication rate of HCF surgery in the French Bulldog is significant.

Exploring the full range of N⋯I⋯X halogen-bonding interactions within a single compound using pressure.

The response of the trimethylammonium-iodinechloride and diiodide (TMA-ICl/I2) crystal structures have been examined under high pressure using neutron powder diffraction. TMA-ICl exhibits impressive pressure-driven electronic flexibility, where the N⋯I-Cl interactions progressively encompass all the distances represented in analogous structures recorded in the Cambridge Structural Database. Comparison with the TMA-I2 complex reveals that this flexibility is owed to the electronegativity of the chlorine atom which induces increased distortion of the iodine electron cloud. This structural flexibility may be influential in the future design of functional molecular materials.

Progressing, not regressing: A possible solution to the problem of regression to the mean in unconscious processing studies.

How convincing is current evidence for unconscious processing? Recently, a major criticism suggested that some, if not much, of this evidence might be explained by a mere statistical phenomenon: regression to the mean (RttM). Excluding participants based on an awareness assessment is a common practice in studies of unconscious processing, and this post hoc data selection might lead to false effects that are driven by RttM for aware participants wrongfully classified as unaware. Here, we examined this criticism using both simulations and data from 12 studies probing unconscious processing (35 effects overall). In line with the original criticism, we confirmed that the reliability of awareness measures in the field is concerningly low. Yet, using simulations, we showed that reliability measures might be unsuitable for estimating error in awareness measures. Furthermore, we examined other solutions for assessing whether an effect is genuine or reflects RttM; all suffered from substantial limitations, such as a lack of specificity to unconscious processing, lack of power, or unjustified assumptions. Accordingly, we suggest a new nonparametric solution, which enjoys high specificity and relatively high power. Together, this work emphasizes the need to account for measurement error in awareness measures and evaluate its consequences for unconscious processing effects. It further suggests a way to meet the important challenge posed by RttM, in an attempt to establish a reliable and robust corpus of knowledge in studying unconscious processing.

Early Experience and Lessons Learned Using Implanted Hemodynamic Monitoring in Patients With Fontan Circulation.

BACKGROUND: Data on the use of implanted hemodynamic monitoring (IHM) in patients with Fontan circulation are limited. This study reports our experience using the CardioMEMS HF system in adults with Fontan circulation. METHODS AND RESULTS: This single-center, retrospective study evaluated heart failure hospitalizations, procedural complications, and device-related complications in patients with Fontan circulation referred for IHM placement (2015-2022). The association of pulmonary artery pressure (by most recent catheterization and median IHM pressure within 30 days of placement) with both death and follow-up Model for End-Stage Liver Disease Excluding International Normalized Ratio score were evaluated. Of 18 patients referred for IHM placement, 17 were successful (median age, 30 [range 21-48] years, 6 women). Procedural complications (access site hematomas, pulmonary artery staining) occurred in 3 patients, without device-related procedural complications. In follow-up (median, 35 [range, 6-83] months), 1 patient developed a pulmonary embolism (possibly device-related). Heart failure hospitalizations/year were similar before and after IHM (median, 1 [interquartile range, 0-1.0] versus 0.6 [0-2.3]; P=0.268), though only 46% of heart failure hospitalizations had associated IHM transmissions. IHM pressures were associated with Model for End-Stage Liver Disease Excluding International Normalized Ratio scores (R2=0.588, P<0.001), though catheterization pressures were not (R2=0.140, P=0.139). The long-term mortality rate was 53% in this cohort. On unadjusted survival analysis, IHM pressures ≥18 mm Hg were associated with mortality (log rank P=0.041), which was not reproduced with catheterization pressures (log rank P=0.764). CONCLUSIONS: In patients with Fontan circulation, IHM did not reduce heart failure hospitalizations, though patient adherence to transmission was low. Device-related complications were low. IHM pressures may better represent real-life conditions compared with catheterization given associations with mortality and Model for End-Stage Liver Disease Excluding International Normalized Ratio score.

Integrated information theory (IIT) 4.0: Formulating the properties of phenomenal existence in physical terms.

This paper presents Integrated Information Theory (IIT) 4.0. IIT aims to account for the properties of experience in physical (operational) terms. It identifies the essential properties of experience (axioms), infers the necessary and sufficient properties that its substrate must satisfy (postulates), and expresses them in mathematical terms. In principle, the postulates can be applied to any system of units in a state to determine whether it is conscious, to what degree, and in what way. IIT offers a parsimonious explanation of empirical evidence, makes testable predictions concerning both the presence and the quality of experience, and permits inferences and extrapolations. IIT 4.0 incorporates several developments of the past ten years, including a more accurate formulation of the axioms as postulates and mathematical expressions, the introduction of a unique measure of intrinsic information that is consistent with the postulates, and an explicit assessment of causal relations. By fully unfolding a system's irreducible cause-effect power, the distinctions and relations specified by a substrate can account for the quality of experience.

A majority of trauma-related deep venous thromboses resolve prior to discharge.

Post-traumatic DVTs present unique challenges in patient populations with specific high-risk injury patterns. Duplex ultrasound (US) can be used to assess evolution of DVTs and may guide treatment for high-risk patients. We hypothesized that many DVTs resolve during the initial admission. Weekly duplex US are ordered on all trauma inpatients regardless of prior DVT at our facility. We reviewed US and outcomes data on all patients with lower extremity DVTs at our Level I trauma center from January 2012-December 2021. 392 patients were diagnosed with lower extremity DVT by US. 261 (67%) patients received follow-up US with a mean time to repeat US of 6 days. Of these, 91 (35%) patients experienced DVT resolution prior to the first follow-up US, and 141 (54%) patients experienced resolution prior to discharge. Mean time to resolution was 10 days. Over 50% of DVTs resolve before discharge and are detected by US. Further studies and post-discharge follow-up are needed to determine if patients with resolved DVTs can be managed without therapeutic anticoagulation.

Inhalation Injury: Which Providers Can Assess the Need for Intubation?

Previous studies have suggested that many burn patients undergo unnecessary intubation due to concern for inhalation injury. We hypothesized that burn surgeons would intubate burn patients at a lower rate than non-burn acute care surgeons (ACSs). We performed a retrospective cohort study of all patients admitted to an American Burn Association-verified burn center who presented emergently following burn injury from June 2015 to December 2021. Patients excluded include polytrauma patients, isolated friction burns, and patients intubated prior to hospital arrival. Our primary outcome was intubation rates between burn and non-burn ACSs. 388 patients met inclusion criteria. 240 (62%) patients were evaluated by a burn provider and 148 (38%) were evaluated by a non-burn provider; the groups were well-matched. In total, 73 (19%) of patients underwent intubation. There was no difference in the rate of emergent intubation, diagnosis of inhalation injury on bronchoscopy, time to extubation, or incidence of extubation within 48 hours between burn and non-burn ACSs. We found no difference between burn and non-burn ACSs in the airway evaluation and management of burn patients. Surgical providers with acute care surgery backgrounds and Advanced Trauma Life Support training are well-equipped for initial airway management in burn patients. Further studies should seek to compare other types of provider groups to identify opportunities for intervention and education in preventing unnecessary intubations.

Cross-Border Antibiotic Resistance Patterns in Burn Patients.

Background: Antimicrobial resistance (AMR) is a growing problem worldwide, with differences in regional resistance patterns partially driven by local variance in antibiotic stewardship. Trauma patients transferring from Mexico have more AMR than those injured in the United States; we hypothesized a similar pattern would be present for burn patients. Patients and Methods: The registry of an American Burn Association (ABA)-verified burn center was queried for all admissions for burn injury January 2015 through December 2019 with hospital length-of-stay (LOS) longer than seven days. Patients were divided into two groups based upon burn location: United States (USA) or Mexico (MEX). All bacterial infections were analyzed. Results: A total of 73 MEX and 826 USA patients were included. Patients had a similar mean age (40.4 years MEX vs. 42.2 USA) and gender distribution (69.6% male vs. 64.4%). The MEX patients had larger median percent total body surface area burned (%TBSA; 11.1% vs. 4.3%; p ≤ 0.001) and longer hospital LOS (18.0 vs. 13.0 days; p = 0.028). The MEX patients more often had respiratory infections (16.4% vs. 7.4%; p = 0.046), whereas rates of other infections were similar. The MEX patients had higher rates of any resistant organism (47.2% of organisms MEX vs. 28.1% USA; p = 0.013), and were more likely to have resistant infections on univariable analysis; however, on multivariable analysis country of burn was no longer significant. Conclusions: Antimicrobial resistance is more common in burn patients initially burned in Mexico than those burned in the United States, but location was not a predictor of resistance compared to other traditional burn-related factors. Continuing to monitor for AMR regardless of country of burn remains critical.

Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients.

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study.

An Algorithm of Nonparametric Quantile Regression.

Extreme events, such as earthquakes, tsunamis, and market crashes, can have substantial impact on social and ecological systems. Quantile regression can be used for predicting these extreme events, making it an important problem that has applications in many fields. Estimating high conditional quantiles is a difficult problem. Regular linear quantile regression uses an L 1 loss function [Koenker in Quantile regression, Cambridge University Press, Cambridge, 2005], and the optimal solution of linear programming for estimating coefficients of regression. A problem with linear quantile regression is that the estimated curves for different quantiles can cross, a result that is logically inconsistent. To overcome the curves crossing problem, and to improve high quantile estimation in the nonlinear case, this paper proposes a nonparametric quantile regression method to estimate high conditional quantiles. A three-step computational algorithm is given, and the asymptotic properties of the proposed estimator are derived. Monte Carlo simulations show that the proposed method is more efficient than linear quantile regression method. Furthermore, this paper investigates COVID-19 and blood pressure real-world examples of extreme events by using the proposed method.

Contemporary management and outcomes of penetrating colon injuries: Validation of the 2020 AAST Colon Organ Injury Scale.

INTRODUCTION: The American Association for the Surgery of Trauma Colon Organ Injury Scale (OIS) was updated in 2020 to include a separate OIS for penetrating colon injuries and included imaging criteria. In this multicenter study, we describe the contemporary management and outcomes of penetrating colon injuries and hypothesize that the 2020 OIS system correlates with operative management, complications, and outcomes. METHODS: This was a retrospective study of patients presenting to 12 Level 1 trauma centers between 2016 and 2020 with penetrating colon injuries and Abbreviated Injury Scale score of <3 in other body regions. We assessed the association of the new OIS with surgical management and clinical outcomes and the association of OIS imaging criteria with operative criteria. Bivariate analysis was done with χ 2 , analysis of variance, and Kruskal-Wallis, where appropriate. Multivariable models were constructed in a stepwise selection fashion. RESULTS: We identified 573 patients with penetrating colon injuries. Patients were young and predominantly male; 79% suffered a gunshot injury, 11% had a grade V destructive injury, 19% required ≥6 U of transfusion, 24% had an Injury Severity Score of >15, and 42% had moderate-to-large contamination. Higher OIS was independently associated with a lower likelihood of primary repair, higher likelihood of resection with anastomosis and/or diversion, need for damage-control laparotomy, and higher incidence of abscess, wound infection, extra-abdominal infections, acute kidney injury, and lung injury. Damage control was independently associated with diversion and intra-abdominal and extra-abdominal infections. Preoperative imaging in 152 (27%) cases had a low correlation with operative findings ( κ coefficient, 0.13). CONCLUSION: This is the largest study to date of penetrating colon injuries and the first multicenter validation of the new OIS specific to these injuries. While imaging criteria alone lacked strong predictive value, operative American Association for the Surgery of Trauma OIS colon grade strongly predicted type of interventions and outcomes, supporting use of this grading scale for research and clinical practice. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

A survey of neurophysiological differentiation across mouse visual brain areas and timescales.

Neurophysiological differentiation (ND), a measure of the number of distinct activity states that a neural population visits over a time interval, has been used as a correlate of meaningfulness or subjective perception of visual stimuli. ND has largely been studied in non-invasive human whole-brain recordings where spatial resolution is limited. However, it is likely that perception is supported by discrete neuronal populations rather than the whole brain. Therefore, here we use Neuropixels recordings from the mouse brain to characterize the ND metric across a wide range of temporal scales, within neural populations recorded at single-cell resolution in localized regions. Using the spiking activity of thousands of simultaneously recorded neurons spanning 6 visual cortical areas and the visual thalamus, we show that the ND of stimulus-evoked activity of the entire visual cortex is higher for naturalistic stimuli relative to artificial ones. This finding holds in most individual areas throughout the visual hierarchy. Moreover, for animals performing an image change detection task, ND of the entire visual cortex (though not individual areas) is higher for successful detection compared to failed trials, consistent with the assumed perception of the stimulus. Together, these results suggest that ND computed on cellular-level neural recordings is a useful tool highlighting cell populations that may be involved in subjective perception.

Up and over: Consequences of raising the United States-Mexico border wall height.

OBJECTIVES: San Diego County's geographic location lends a unique demographic of migrant patients injured by falls at the United States-Mexico border. To prevent migrant crossings, a 2017 Executive Order allocated funds to increase the southern California border wall height from 10 ft to 30 ft, which was completed in December 2019. We hypothesized that the elevated border wall height is associated with increased major trauma, resource utilization, and health care costs. METHODS: Retrospective trauma registry review of border wall falls was performed by the two Level I trauma centers that admit border fall patients from the southern California border from January 2016 to June 2022. Patients were assigned to either "pre-2020" or "post-2020" subgroups based upon timing of completion of the heightened border wall. Total number of admissions, operating room utilization, hospital charges, and hospital costs were compared. RESULTS: Injuries from border wall falls grew 967% from 2016 to 2021 (39 vs. 377 admissions); this percentage is expected to be supplanted in 2022. When comparing the two subgroups, operating room utilization (175 vs. 734 total operations) and median hospital charges per patient ($95,229 vs. $168,795) have risen dramatically over the same time period. Hospital costs increased 636% in the post-2020 subgroup ($11,351,216 versus $72,172,123). The majority (97%) of these patients are uninsured at admission, with costs largely subsidized by federal government entities (57%) or through state Medicaid enrollment postadmission (31%). CONCLUSION: The increased height of the United States-Mexico border wall has resulted in record numbers of injured migrant patients, placing novel financial and resource burdens on already stressed trauma systems. To address this public health crisis, legislators and health care providers must conduct collaborative, apolitical discussions regarding the border wall's efficacy as a means of deterrence and its impact on traumatic injury and disability. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

System Integrated Information.

Integrated information theory (IIT) starts from consciousness itself and identifies a set of properties (axioms) that are true of every conceivable experience. The axioms are translated into a set of postulates about the substrate of consciousness (called a complex), which are then used to formulate a mathematical framework for assessing both the quality and quantity of experience. The explanatory identity proposed by IIT is that an experience is identical to the cause-effect structure unfolded from a maximally irreducible substrate (a Φ-structure). In this work we introduce a definition for the integrated information of a system (φs) that is based on the existence, intrinsicality, information, and integration postulates of IIT. We explore how notions of determinism, degeneracy, and fault lines in the connectivity impact system-integrated information. We then demonstrate how the proposed measure identifies complexes as systems, the φs of which is greater than the φs of any overlapping candidate systems.

Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension.

BACKGROUND: Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels. METHODS: In this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary end point was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group. RESULTS: A total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of -20.3 mm Hg, -17.5 mm Hg, -12.1 mm Hg, and -9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was -11.0 mm Hg (95% confidence interval [CI], -16.4 to -5.5; P<0.001), and the difference in this change between the 1-mg group and the placebo group was -8.1 mm Hg (95% CI, -13.5 to -2.8; P = 0.003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug. CONCLUSIONS: Patients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure. (Funded by CinCor Pharma; BrigHTN ClinicalTrials.gov number, NCT04519658.).

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum.

Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brain's ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses. However, whether these synapses are affected by sleep and wake is unknown. Here, we used serial block face scanning electron microscopy to obtain the full 3D reconstruction of more than 7000 spines and their parallel fiber synapses in the mouse posterior vermis. This analysis was done in mice whose cortical and hippocampal synapses were previously measured, revealing that average synaptic size was lower after sleep compared to wake with no major changes in synapse number. Here, instead, we find that while the average size of parallel fiber synapses does not change, the number of branched synapses is reduced in half after sleep compared to after wake, corresponding to ~16% of all spines after wake and ~8% after sleep. Branched synapses are harbored by two or more spines sharing the same neck and, as also shown here, are almost always contacted by different parallel fibers. These findings suggest that during wake, coincidences of firing over parallel fibers may translate into the formation of synapses converging on the same branched spine, which may be especially effective in driving Purkinje cells to fire. By contrast, sleep may promote the off-line pruning of branched synapses that were formed due to spurious coincidences.

Algorithmic identification of atypical diabetes in electronic health record (EHR) systems.

AIMS: Understanding atypical forms of diabetes (AD) may advance precision medicine, but methods to identify such patients are needed. We propose an electronic health record (EHR)-based algorithmic approach to identify patients who may have AD, specifically those with insulin-sufficient, non-metabolic diabetes, in order to improve feasibility of identifying these patients through detailed chart review. METHODS: Patients with likely T2D were selected using a validated machine-learning (ML) algorithm applied to EHR data. "Typical" T2D cases were removed by excluding individuals with obesity, evidence of dyslipidemia, antibody-positive diabetes, or cystic fibrosis. To filter out likely type 1 diabetes (T1D) cases, we applied six additional "branch algorithms," relying on various clinical characteristics, which resulted in six overlapping cohorts. Diabetes type was classified by manual chart review as atypical, not atypical, or indeterminate due to missing information. RESULTS: Of 114,975 biobank participants, the algorithms collectively identified 119 (0.1%) potential AD cases, of which 16 (0.014%) were confirmed after expert review. The branch algorithm that excluded T1D based on outpatient insulin use had the highest percentage yield of AD (13 of 27; 48.2% yield). Together, the 16 AD cases had significantly lower BMI and higher HDL than either unselected T1D or T2D cases identified by ML algorithms (P<0.05). Compared to the ML T1D group, the AD group had a significantly higher T2D polygenic score (P<0.01) and lower hemoglobin A1c (P<0.01). CONCLUSION: Our EHR-based algorithms followed by manual chart review identified collectively 16 individuals with AD, representing 0.22% of biobank enrollees with T2D. With a maximum yield of 48% cases after manual chart review, our algorithms have the potential to drastically improve efficiency of AD identification. Recognizing patients with AD may inform on the heterogeneity of T2D and facilitate enrollment in studies like the Rare and Atypical Diabetes Network (RADIANT).

Increase in NREM sleep slow waves following injections of sodium oxybate in the mouse cerebral cortex and the role of somatostatin-positive interneurons.

The systemic administration of sodium oxybate (SXB), the sodium salt of gamma-hydroxybutyric acid, promotes slow wave activity (SWA, 0.5-4 Hz EEG power) and increases non-rapid eye movement (NREM) sleep. These effects are mediated by the widely expressed GABAb receptors, and thus, the brain areas targeted by SXB remain unclear. Because slow waves are mainly a cortical phenomenon, we tested here whether systemic SXB promotes SWA by acting directly on the cortex. Moreover, because somatostatin (SOM) + cortical interneurons play a key role in SWA generation, we also assessed their contribution to the effects of SXB. In adult SOM-Cre mice, the injection of SXB in left secondary motor cortex increased SWA during NREM sleep in the first 30 min post-injection (11 mice: either sex). SWA, the amplitude and frequency of the slow waves, and the frequency of the OFF periods increased ipsilaterally and contralaterally to the SXB injection in frontal and parietal cortex. All these changes disappeared when the intracortical injection of SXB was preceded by the chemogenetic inhibition of the SOM+ cells. Thus, SXB may promote the slow waves of NREM sleep, at least in part, by acting directly on the cortex, and this effect involves GABAergic SOM+ interneurons. Our working hypothesis is that SXB potentiates the ability of these cells to inhibit all other cortical cell types via a GABAb mechanism, thus promoting the transition from ON to OFF periods during NREM sleep.

Delayed union, non-union and mal-union in 442 dogs.

OBJECTIVES: (1) To estimate the prevalence of delayed union, non-union and mal-union in canine fractures; (2) to describe fracture, demographic, and treatment characteristics for these outcomes; (3) to identify risk factors for delayed or non-union. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Four hundred and forty two dogs (461 fractures). METHODS: A review was conducted of clinical records and radiographs from 2 teaching hospitals. "Union," "delayed union," "non-union" and "mal-union" were defined, and fracture, demographic, treatment, and outcome variables described. Differences in proportions or medians between "union," "delayed union" and "non-union" were tested using χ2 and Mann-Whitney U-tests for categorical and continuous variables respectively. Potential explanatory variables for "delayed or non-union" were tested using logistic regression to identify risk factors. RESULTS: Median radiographic follow up was 53 days (14-282). Delayed union occurred in 13.9% of fractures (64/461), non-union in 4.6% (21/461), and mal-union in 0.7% (3/461). Risk factors for delayed or non-union were age (OR 1.21, 95% CI 1.12-1.31); comminuted fracture (OR 4.24, 95% CI 2.4-7.5); treatment with bone graft (all types) (OR 3.32, 95% CI 1.3-8.5); surgical site infection (OR 3.24, 95% CI 1.17-8.97), and major implant failure (OR 12.94, 95% CI 5.06-33.1). CONCLUSION: Older dogs, dogs with comminuted fractures, surgical site infection, or major implant failure were at increased odds of delayed or non-union. Radius and ulna fractures in toy breed dogs were not at increased odds of delayed or non-union. CLINICAL SIGNIFICANCE: The identified risk factors should inform fracture planning and prognosticating. The prognosis for radial fractures in toy breeds appears better than historically believed.