Anti-Thymocyte Globulin as a Therapy for Chronic Lung Allograft Dysfunction: A Single-Center Experience.

INTRODUCTION: Anti-thymocyte globulin (ATG) is a polyclonal antibody formulation which has been used as a second-line therapy for chronic lung allograft dysfunction (CLAD). Limited data exist evaluating its efficacy; however, several single-center retrospective studies have variably demonstrated either improvement or stabilization of spirometry parameters after administration of ATG. ATG has been in use at UT Southwestern for treatment of CLAD since at least 2010; here, we seek to evaluate the effectiveness of this intervention at our center.  METHODS: A retrospective chart review was conducted of a total of 136 patients who underwent lung transplantation at UT Southwestern Medical Center between 2010 and 2022. Of these, 72 patients had received ATG specifically for treatment of CLAD, and the remaining 64 had never received ATG. Two separate analyses were performed: in the first, among those who received ATG for CLAD, spirometry data from the 6 months preceding and following ATG administration were reviewed and rates of change in FEV1 were calculated for each time period. Descriptive statistics were performed to summarize the baseline clinical characteristics and outcomes after ATG, with patients classified as having either a full response (positive rate of change in FEV1) or partial response (>20% attenuation in rate of FEV1 decline) to ATG.  In the second analysis, survival was described among those who received ATG for CLAD and comparison was provided between propensity-score matched cohorts from the ATG and non-ATG groups. RESULTS: Of the 63 patients who received ATG for treatment of CLAD (and had adequate spirometry measurements available to trend FEV1), 49 (77.8%) had at least a partial response to therapy; 8 (12.7%) experienced an overall improvement in FEV1. Response to ATG was found to be associated with a more rapid rate of pre-ATG decline in FEV1; no other baseline parameters were found to be predictive of a response to ATG. Median post-CLAD graft survival was 31.7 months among those who received ATG, and only baseline absolute neutrophil count was found to be associated with worse post-CLAD graft survival among this group. CONCLUSION: Anti-thymocyte globulin therapy, when given for CLAD, was associated with at least a modest attenuation in rate of FEV1 decline in most patients but only rarely preceded an absolute improvement in FEV1. Further study is warranted to better define the role for ATG in treatment of CLAD, a challenging disease state with limited therapeutics available.

Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice.

BACKGROUND: We have developed a mouse model of Parenteral Nutrition Associated Liver Disease in which PN infusion results in cholestatic liver injury. In the liver, the master circadian genes Arntl/Bmal drive rhythmic gene expression and regulate circadian expression of hepatic functions including bile acid synthesis. The aim of this study was to examine the effect of continuous PN on ileal and hepatic expression of circadian regulatory (CR) genes, FXR signaling and bile acid synthesis in mice. METHODS: WT mice were exposed to continuous soy oil lipid emulsion-based PN infusion through a central venous catheter for 4 days (PN). Water was provided ad libitum, but no nutrients were provided enterally. On d4, mice were sacrificed every 6 hours (7AM, 1PM, 7PM and 1AM), and ileal, hepatic tissue and serum harvested. From tissue samples, the relative expression of circadian transcription factors and FXR signaling was assessed. RESULTS: Administration of 4d PN increased hepatic injury, inflammatory cytokine expression and gut permeability. In the ileum, PN activated FXR and induced expression of Fgf15 and Nr0b2. In the liver, expression of FXR-downstream targets was dysregulated. PN administrations impacted hepatic and ileal circadian transcription factor mRNA expression which was discordant between the two organs. CONCLUSIONS: Dysregulation of circadian regulatory machinery is in part due to discordance of the gut-liver axis during PN. Pharmacologic targeting of CR as a therapeutic strategy for PNALD thus deserves further investigation.

Methadone Initiation in the Emergency Department for Opioid Use Disorder.

Introduction: Overdose deaths from high-potency synthetic opioids, including fentanyl and its analogs, continue to rise along with emergency department (ED) visits for complications of opioid use disorder (OUD). Fentanyl accumulates in adipose tissue; although rare, this increases the risk of precipitated withdrawal in patients upon buprenorphine initiation. Many EDs have implemented medication for opioid use disorder (MOUD) programs using buprenorphine. However, few offer methadone, a proven therapy without the risk of precipitated withdrawal associated with buprenorphine initiation. We describe the addition of an ED-initiated methadone treatment pathway and compared its 72-hour follow-up outpatient treatment engagement rates to our existing ED-initiated buprenorphine MOUD program. Methods: We expanded our ED MOUD program with a methadone treatment pathway. From February 20-September 19, 2023, we screened 20,504 ED arrivals; 5.1% had signs of OUD. We enrolled 61 patients: 28 in the methadone; and 33 in the buprenorphine pathways. For patients who screened positive for opioid use, shared decision-making was employed to determine whether buprenorphine or methadone therapy was more appropriate. Patients in the methadone pathway received their first dose of up to 30 milligrams (mg) of methadone in the ED. Two additional methadone doses of up to 40 mg were dispensed at the time of the ED visit and held in the department, allowing patients to return each day for observed dosing until intake at an opioid treatment program (OTP). We compared 72-hour rates of outpatient follow-up treatment engagement at the OTP (for those on methadone) or at the addiction treatment center (ATC) (for those on buprenorphine) for the two treatment pathways. Results: Of the 28 patients enrolled in the methadone pathway, 12 (43%) successfully engaged in follow-up treatment at the OTP. Of the 33 patients enrolled in the buprenorphine pathway, 15 (45%) successfully engaged in follow-up treatment at the ATC (relative risk 1.06; 95% confidence interval 0.60-1.87). Conclusion: Methadone initiation in the ED to treat patients with OUD resulted in similar 72-hour follow-up outpatient treatment engagement rates compared to ED-buprenorphine initiation, providing another viable option for MOUD.

Microsporum canis Causes Cutaneous and Extracutaneous Feline Dermatophytic Pseudomycetomas: Molecular Identification and Clinicopathological Characteristics.

Dermatophytic pseudomycetoma (DPM) is a rarely reported invasive fungal infection of humans and animals, especially cats. This study aimed to identify dermatophytes, breed associations, and the frequency of extracutaneous (EC) involvement in feline DPM. Electronic records and formalin-fixed paraffin-embedded tissue (FFPET) from 32 suspected DPM cases in 30 cats were retrieved from a diagnostic laboratory between 2018 and 2024. To confirm DPM and molecular identity, DNA was extracted from FFPET for ITS2 sequencing, and immunohistochemistry was performed on PCR-negative cases. All cases were confirmed as DPM. Microsporum canis was the only dermatophyte identified. The sensitivity and specificity of ITS2 sequencing for M. canis identification in FFPET were 22/32 (68.8%) and 21/22 (95.5%), respectively. Exotic (36.7%) and Persian (23.3%) but not British breeds (26.3%) were over-represented compared to feline admissions at an affiliated veterinary hospital (8.5%, p < 0.001; 3%, p < 0.001; 21.6%, p = 0.817, respectively). Five cases (16.7%) had EC lesions; two had intra-abdominal masses; two had oral cavity masses, including one which extended into the cranial vault; and one had superficial cervical lymph node invasion. Exotic and Persian breeds are over-represented for DPM and M. canis is the primary cause. EC lesions of DPM may occur more commonly than previously thought.

Comparing Treatment Effectiveness and Patient-Reported Outcome Measures of Four Treatment Options for Obstructive Sleep Apnea.

BACKGROUND: Continuous positive airway pressure (CPAP), mandibular advancement device (MAD), upper airway stimulation (UAS), and maxillomandibular advancement (MMA) are techniques to reduce apnea hypopnea index (AHI) in obstructive sleep apnea (OSA) patients. Current literature does not include a direct comparison of the 4 methods. PURPOSE: The purpose of this study is to measure and compare the efficacy of 4 common OSA treatments: CPAP, MAD, UAS, MMA. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study examines data from 119 patients treated at Thomas Jefferson University Hospital in Philadelphia receiving CPAP, MAD, UAS, or MMA between January 2018 and December 2020. Patients were excluded for significant medical comorbidities, body mass index ≥45, cognitive limitations, central/mixed apnea history, or pregnancy. PREDICTOR VARIABLES: The primary predictor variable was type of OSA intervention: CPAP, MAD, UAS, MMA. Treatments were assigned by treating physicians per their presenting OSA severity. MAIN OUTCOME VARIABLES: The primary outcome variable was efficacy defined as the therapeutic response to treatment measured using mean disease alleviation, a calculated variable (percentage) which employs post-treatment AHI adjusted by compliance (a measure of a patient's device use). Secondary therapeutic measures included remaining AHI and patient-reported outcome measures: Epworth Sleepiness Scale, Sleep Apnea Quality of Life Index, Patient-reported Apnea Questionnaire. COVARIATES: Demographic covariates included age, sex, height, weight, socioeconomic status, level of education, neck size, race, and body mass index. Clinical covariates included pretreatment AHI, AHI change, O2 nadir, adjusted compliance, and compliance. ANALYSES: Multivariate statistics were computed with alpha level of 0.05, including a regression with the primary outcome variables, treatment variables, and potential covariates. RESULTS: The sample included 119 subjects (mean age = 56.12, standard deviation [SD] = 5.81) with males at n = 72 (60%). MMA demonstrated greatest mean disease alleviation (M = 36.08, SD = 28.56), compared to UAS (M = 22.88, SD = 3.16), MAD (M = 6.80, SD = 8.13), and CPAP (M = 5.00, SD = 14.80), analysis of variance: P < .001. CONCLUSION AND RELEVANCE: Both surgical treatments displayed significantly greater effectiveness than CPAP and MAD, suggesting that offering surgical alternatives sooner, particularly to those with severe OSA, may be logical in formulating more effective treatment guidelines.

Transoral Robotic Surgery Versus Hypoglossal Nerve Stimulation for OSA: A Cost Analysis Study.

BACKGROUND: Transoral robotic surgery (TORS) lingual tonsillectomy and hypoglossal nerve stimulation (HGNS) are effective surgical interventions for well-selected patients with obstructive sleep apnea (OSA) intolerant to continuous positive airway pressure (CPAP) therapy. Previous publications have demonstrated that HGNS patients have a lower postoperative apnea-hypopnea index (AHI) and length of hospital stay than TORS patients. No prior study has investigated the differences in costs between HGNS and TORS. OBJECTIVES: This study aims to compare surgery-related costs in patients undergoing HGNS versus TORS lingual tonsillectomy for OSA intolerant to CPAP. METHODS: A retrospective study on OSA patients intolerant to CPAP that underwent HGNS or TORS from 2015 to 2022 at a tertiary care center. Cost was defined as the dollar amount associated with providing a specific service prior to the application of insurance. RESULTS: This study included 395 patients (375 UAS and 20 TORS). Average total cost was significantly higher in the UAS group than the TORS group (UAS: $25,582.60; TORS: $5832.60; p < 0.001). Operating room costs were also significantly higher in the UAS group (UAS: $1978.20; TORS: $1490.90; p = 0.001). The TORS cohort averaged higher costs for pharmacy (UAS: $201.30; TORS: $416.60; p < 0.001) and anesthesia (UAS: $139.00; TORS: $307.60; p < 0.001). DISCUSSION: The total cost was significantly higher in the UAS group compared to the TORS group. When making management decisions, it is important to consider the cost of care provided as well as patient-centered outcomes to optimize the value of care. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Cation Vacancies Enable Anion Redox in Li Cathodes.

Conventional Li-ion battery intercalation cathodes leverage charge compensation that is formally associated with redox on the transition metal. Employing the anions in the charge compensation mechanism, so-called anion redox, can yield higher capacities beyond the traditional limitations of intercalation chemistry. Here, we aim to understand the structural considerations that enable anion oxidation and focus on processes that result in structural changes, such as the formation of persulfide bonds. Using a Li-rich metal sulfide as a model system, we present both first-principles simulations and experimental data that show that cation vacancies are required for anion oxidation. First-principles simulations show that the oxidation of sulfide to persulfide only occurs when a neighboring vacancy is present. To experimentally probe the role of vacancies in anion redox processes, we introduce vacancies into the Li2TiS3 phase while maintaining a high valency of Ti. When the cation sublattice is fully occupied and no vacancies can be formed through transition metal oxidation, the material is electrochemically inert. Upon introduction of vacancies, the material can support high degrees of anion redox, even in the absence of transition metal oxidation. The model system offers fundamental insights to deepen our understanding of structure-property relationships that govern reversible anion redox in sulfides and demonstrates that cation vacancies are required for anion oxidation, in which persulfides are formed.

Development of a Novel Classification Approach for Cow Behavior Analysis Using Tracking Data and Unsupervised Machine Learning Techniques.

Global Positioning Systems (GPSs) can collect tracking data to remotely monitor livestock well-being and pasture use. Supervised machine learning requires behavioral observations of monitored animals to identify changes in behavior, which is labor-intensive. Our goal was to identify animal behaviors automatically without using human observations. We designed a novel framework using unsupervised learning techniques. The framework contains two steps. The first step segments cattle tracking data using state-of-the-art time series segmentation algorithms, and the second step groups segments into clusters and then labels the clusters. To evaluate the applicability of our proposed framework, we utilized GPS tracking data collected from five cows in a 1096 ha rangeland pasture. Cow movement pathways were grouped into six behavior clusters based on velocity (m/min) and distance from water. Again, using velocity, these six clusters were classified into walking, grazing, and resting behaviors. The mean velocity for predicted walking and grazing and resting behavior was 44, 13 and 2 min/min, respectively, which is similar to other research. Predicted diurnal behavior patterns showed two primary grazing bouts during early morning and evening, like in other studies. Our study demonstrates that the proposed two-step framework can use unlabeled GPS tracking data to predict cattle behavior without human observations.

Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution.

With a growing body of evidence that now links environmental pollution to adverse cardiovascular disease (CVD) outcomes, pollution has emerged as an important risk factor for CVD. There is thus an urgent need to better understand the role of pollution in CVD, key pathophysiological mechanisms, and to raise awareness among health care providers, the scientific community, the general population, and regulatory authorities about the CV impact of pollution and strategies to reduce it. This article is part 2 of a 2-part state-of-the-art review on the topic of pollution and CVD-herein we discuss major environmental pollutants and their effects on CVD, highlighting pathophysiological mechanisms, and strategies to reduce CVD risk.

Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 50 years, there has been a substantial decline in the incidence of CVD and related mortality in high-income countries, largely due to the mitigation of modifiable risk factors such as smoking, hypertension, and diabetes. However, a significant burden of CVD remains in low- to middle-income countries, despite their lower prevalence of traditional risk factors; other environmental factors, particularly pollution, play a significant role in this attributable risk. Mounting evidence underscores a strong association between pollution and adverse health effects, including CVD. This article is part 1 of a 2-part state-of-the-art review and discusses air pollution and its adverse effects on CVD, highlighting pathophysiological mechanisms and methods to reduce air pollution and exposure to these pollutants.

A Systematic Review of Clinical Outcomes of Pedicled Flap Repairs of the Knee Extensor Mechanism.

BACKGROUND: Rupture of the extensor mechanism of the knee has severe functional morbidity, and repair can be complicated by infection, allograft degeneration, and recurrent rupture. Techniques of autologous tissue repair utilizing pedicled flaps such as the gastrocnemius offer vascularized methods of reconstruction, with potentially diminished complication rates. The goal of this study was to evaluate the functional outcomes and complications associated with pedicled flap repair of the knee extensor mechanism. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Publications that focused on local myocutaneous flaps as a means for reconstruction were included. Causes for knee extensor mechanism deficit, flap characteristics, ambulation rate, changes in range of motion pre- and postoperation, and postoperative complications were analyzed. Technique reports including primary suture repairs, synthetic mesh, and allograft use were excluded. RESULTS: An initial 119 studies were identified, with final review of 22 observational studies encompassing 128 cases of pedicled flap reconstructions. The gastrocnemius (88.2%, n = 113), quadriceps (6.3%, n = 8), and a combination of the vastus and gastrocnemius flaps (5.5%, n = 7), were the most frequently utilized flaps. Functional outcomes were favorable with 87.2% of patients achieving ambulation without external support. Variability in range of motion outcomes across different flap may be secondary to the patient characteristics as well as extent of initial injury. CONCLUSIONS: Autologous pedicle flap reconstruction of the knee extensor mechanism emerges as a viable option for cases characterized by extensive defects and insufficient soft tissue coverage, which are not amenable to direct suture repairs or allografts. Postoperative assessments revealed that the majority of patients experienced improved ambulation status, with no instances of deterioration noted among the patients.

Conceptualizing impulsivity as a construct in relation to posttraumatic stress disorder symptom severity among women.

Despite the established association between posttraumatic stress disorder (PTSD) and impulsivity, the literature is limited regarding impulsivity as a multifaceted construct. That is, the field's understanding of how PTSD symptoms may increase particular impulsive tendencies and behaviors is constrained by examining impulsivity solely as an umbrella term. The aim of the present study was to determine if there are differential associations between PTSD symptom severity and various components of impulsivity across multiple self-report measures. A sample of 215 undergraduate women (M age = 19.77 years, SD = 1.91, Range: 18-39 years) completed the PTSD Checklist for DSM-5 (PCL-5), Barratt Impulsiveness Scale (BIS-11), short version of the UPPS-P Impulsive Behavior Scale (SUPPS-P), and Delaying Gratification Inventory (DGI). Structural equation modeling was used to examine associations between PTSD symptoms and each measure's subscales. The findings included significant predictions from PTSD symptoms to the BIS-11 Attentional Impulsiveness subscale, ß = .23, SE = .07, 95% CI [.09, .37]; DGI Physical Pleasures, ß = -.24, SE = .07, 95% CI [-.38, -.11], and Achievement subscales, ß = -.19, SE = .08, 95% CI [-.34, -.04]; and the SUPPS-P Positive Urgency, ß = .22, SE = .08, 95% CI [.07, .37], and Negative Urgency subscales, ß = .32, SE = .07, 95% CI [.19, .46]. These results have implications for precision medicine approaches that emphasize targeting these specific facets of impulsivity, with likely downstream effects on health risk behaviors for emerging adult women.

Reducing Voltage Hysteresis in Li-Rich Sulfide Cathodes by Incorporation of Mn.

Conventional intercalation-based cathode materials in Li-ion batteries are based on charge compensation of the redox-active cation and can only intercalate one mole of electron per formula unit. Anion redox, which employs the anion sublattice to compensate charge, is a promising way to achieve multielectron cathode materials. Most anion redox materials still face the problems of slow kinetics and large voltage hysteresis. One potential solution to reduce voltage hysteresis is to increase the covalency of the metal-ligand bonds. By substituting Mn into the electrochemically inert Li1.33Ti0.67S2 (Li2TiS3), anion redox can be activated in the Li1.33-2y/3Ti0.67-y/3Mn y S2 (y = 0-0.5) series. Not only do we observe substantial anion redox, but the voltage hysteresis is significantly reduced, and the rate capability is dramatically enhanced. The y = 0.3 phase exhibits excellent rate and cycling performance, maintaining 90% of the C/10 capacity at 1C, which indicates fast kinetics for anion redox. X-ray absorption spectroscopy (XAS) shows that both the cation and anion redox processes contribute to the charge compensation. We attribute the drop in hysteresis and increase in rate performance to the increased covalency between the metal and the anion. Electrochemical signatures suggest the anion redox mechanism resembles holes on the anion, but the S K-edge XAS data confirm persulfide formation. The mechanism of anion redox shows that forming persulfides can be a low hysteresis, high rate capability mechanism enabled by the appropriate metal-ligand covalency. This work provides insights into how to design cathode materials with anion redox to achieve fast kinetics and low voltage hysteresis.

Inhibitory control mediates the effect of high intensity interval exercise on food choice.

Exercise is associated with changes in food consumption and cognitive function. The aim of this study was to examine the immediate effects of acute exercise on appetite, food choices, and cognitive processes, and the mediating role of cognitive functioning, namely inhibitory control, working memory, cognitive flexibility and decision making. We compared the effects of high-intensity interval exercise (HIIE) to a resting condition on appetite and food choices, using visual analogue rating scales and a computerised portion selection task. Mediation analysis was performed with exercise/rest condition as a predictor variable and cognitive measures were entered as mediating variables and food choice measures as outcomes. Young women with low activity levels, aged between 18 and 35 years with a body mass index (BMI) between 18 and 25 kg/m², were recruited. Participants (n = 30) demonstrated improved performance on a Stroop task following HIIE compared to the rest session, indicating enhanced attentional inhibition. Accuracy on an N-back task was significantly higher after HIIE, indicating an improvement in working memory and response times on the N-back task were shorter after HIIE, suggesting increased processing speed. Delay discounting for food (but not money) was reduced after HIEE but there were no significant effects on go/no-go task performance. On the trail-making task (a measure of cognitive flexibility), the time difference between trail B and A was significantly lower after HIIE, compared to rest. HIIE reduced rated enjoyment and ideal portion size selection for high energy dense foods. The relationship between exercise and food choices was mediated by inhibition as assessed by the Stoop task. These results suggest that HIIE leads to cognitive benefits and a reduced preference for high-calorie foods and that an enhancement of attentional inhibition may underlie this relationship.

Warming effects on grassland soil microbial communities are amplified in cool months.

Global warming modulates soil respiration (RS) via microbial decomposition, which is seasonally dependent. Yet, the magnitude and direction of this modulation remain unclear, partly owing to the lack of knowledge on how microorganisms respond to seasonal changes. Here, we investigated the temporal dynamics of soil microbial communities over 12 consecutive months under experimental warming in a tallgrass prairie ecosystem. The interplay between warming and time altered (P < 0.05) the taxonomic and functional compositions of microbial communities. During the cool months (January to February and October to December), warming induced a soil microbiome with a higher genomic potential for carbon decomposition, community-level ribosomal RNA operon (rrn) copy numbers, and microbial metabolic quotients, suggesting that warming stimulated fast-growing microorganisms that enhanced carbon decomposition. Modeling analyses further showed that warming reduced the temperature sensitivity of microbial carbon use efficiency (CUE) by 28.7% when monthly average temperature was low, resulting in lower microbial CUE and higher heterotrophic respiration (Rh) potentials. Structural equation modeling showed that warming modulated both Rh and RS directly by altering soil temperature and indirectly by influencing microbial community traits, soil moisture, nitrate content, soil pH, and gross primary productivity. The modulation of Rh by warming was more pronounced in cooler months compared to warmer ones. Together, our findings reveal distinct warming-induced effects on microbial functional traits in cool months, challenging the norm of soil sampling only in the peak growing season, and advancing our mechanistic understanding of the seasonal pattern of RS and Rh sensitivity to warming.

Differential Indirect Effects of Military Sexual Trauma on Posttraumatic Stress Disorder Symptom Clusters via Past-Year Intimate Partner Violence Experiences.

Women who serve in the military are at high risk for experiencing military sexual trauma (MST) and intimate partner violence (IPV), both of which are associated with symptoms of posttraumatic stress disorder (PTSD). To improve understanding of the psychological effects of experiencing multiple forms of interpersonal violence, it is important to identify the ways in which recent IPV experiences differentially increase the risk of specific PTSD symptom clusters for women with a history of MST. We aimed to identify if past-year IPV experiences mediate the relation between MST experiences and PTSD symptom clusters (i.e., intrusions, avoidance, negative alterations in cognitions/mood, hyperarousal) using structural equation modeling. A mail survey was administered to a sample of US female veterans at two time points 12 months apart. Among 198 participants, 108 women (54.5%) reported MST at Time 1, and 73 women (36.9%) reported IPV experiences in the past year at Time 2. PTSD symptom severity ranged from asymptomatic to beyond the diagnostic cutoff for a probable PTSD diagnosis. Past-year IPV experiences significantly mediated the association between MST history and PTSD avoidance symptoms, and MST history and PTSD negative alterations in cognitive/mood symptoms. No significant mediating effect was found for intrusion symptoms or hyperarousal symptoms. These findings can inform evidence-based practices for appropriate screening, assessment, detection, and intervention, including primary and secondary prevention efforts to instrumentally reduce future experiences of violence for female survivors of interpersonal violence.

Device-related outcomes following hypoglossal nerve stimulator implantation.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) has been widely used to treat obstructive sleep apnea in selected patients. Here we evaluate rates of revision and explant related to HGNS implantation and assess types of adverse events contributing to revision and explant. METHODS: Postmarket surveillance data for HGNS implanted between January 1, 2018 and March 31, 2022, were collected. Event rates and risk were calculated using the postmarket surveillance event counts and sales volume over the same period. Indications were categorized for analysis. Descriptive statistics were reported and freedom from explant or revision curves were grouped by year of implantation. RESULTS: Of the 20,881 HGNS implants assessed, rates of explant and revision within the first year were 0.723% and 1.542%, respectively. The most common indication for explant was infection (0.378%) and for revision was surgical correction (0.680%). Of the 5,820 devices with 3-year postimplantation data, the rate of explant was 2.680% and of revision was 3.557%. During this same interval, elective removal (1.478%) was the most common indication, and for revisions, surgical correction (1.134%). CONCLUSIONS: The efficacy of HGNS is comparable in the real world setting to published clinical trial data. Rates of explant and revision are low, supporting a satisfactory safety profile for this technology. CITATION: Moroco AE, Wei Z, Byrd I, et al. Device-related outcomes following hypoglossal nerve stimulator implantation. J Clin Sleep Med. 2024;20(9):1497-1503.

Activation of hepatic acetyl-CoA carboxylase by S-nitrosylation in response to diet.

Nitric oxide (NO), produced primarily by nitric oxide synthase enzymes, is known to influence energy metabolism by stimulating fat uptake and oxidation. The effects of NO on de novo lipogenesis (DNL), however, are less clear. Here we demonstrate that hepatic expression of endothelial nitric oxide synthase is reduced following prolonged administration of a hypercaloric high-fat diet. This results in marked reduction in the amount of S-nitrosylation of liver proteins including notably acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in DNL. We further show that ACC S-nitrosylation markedly increases enzymatic activity. Diminished endothelial nitric oxide synthase expression and ACC S-nitrosylation may thus represent a physiological adaptation to caloric excess by constraining lipogenesis. Our findings demonstrate that S-nitrosylation of liver proteins is subject to dietary control and suggest that DNL is coupled to dietary and metabolic conditions through ACC S-nitrosylation.

When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Session-level effects of cognitive processing therapy and prolonged exposure on individual symptoms of posttraumatic stress disorder among U.S. veterans.

OBJECTIVE: To compare the course of change in individual posttraumatic stress disorder (PTSD) symptoms during prolonged exposure therapy (PE) and cognitive processing therapy (CPT). METHOD: We analyzed data from a previously published randomized clinical trial comparing PE and CPT among male and female U.S. military veterans with PTSD (Schnurr et al., 2022). Using data from a self-rated PTSD symptom measure administered before each therapy session, we evaluated individual symptom change from pretreatment to final therapy session (N = 802). Then, using network intervention analysis, we modeled session-by-session PTSD symptom networks that included treatment allocation (CPT vs. PE) as a node in the networks, allowing us to compare individual symptom change following each session in each treatment. RESULTS: Relative to CPT, PE was associated with greater reduction in 10 PTSD symptoms from first to final session of therapy. Numerous treatment-specific effects on individual symptoms emerged during the treatment period; these session-level effects occurred only in symptoms relatively specific to the diagnosis of PTSD (e.g., avoidance, hypervigilance). PE was associated with greater reduction in avoidance following the introduction and early weeks of imaginal exposure. The treatments yielded comparable effects on trauma-related blame and negative beliefs from pretreatment to final therapy session. However, there were differences in session-level change in these symptoms that may reflect differential timing of interventions that reduce distorted cognitions within each treatment. CONCLUSIONS: Findings may facilitate the shared decision-making process for patients choosing between CPT and PE. Session-level results provide direction for future research on the specific intervention components of CPT and PE. (PsycInfo Database Record (c) 2024 APA, all rights reserved).