Transdiagnostic failure to adapt interoceptive precision estimates across affective, substance use, and eating disorders: A replication and extension of previous results.

Recent Bayesian theories of interoception suggest that perception of bodily states rests upon a precision-weighted integration of afferent signals and prior beliefs. In a previous study, we fit a computational model of perception to behavior on a heartbeat tapping task to test whether aberrant precision-weighting could explain misestimation of cardiac states in psychopathology. We found that, during an interoceptive perturbation designed to amplify afferent signal precision (inspiratory breath-holding), healthy individuals increased the precision-weighting assigned to ascending cardiac signals (relative to resting conditions), while individuals with anxiety, depression, substance use disorders, and/or eating disorders did not. In this pre-registered study, we aimed to replicate and extend our prior findings in a new transdiagnostic patient sample (N=285) similar to the one in the original study. As expected, patients in this new sample were also unable to adjust beliefs about the precision of interoceptive signals - preventing the ability to accurately perceive changes in their cardiac state. Follow-up analyses combining samples from the previous and current study (N=719) also afforded power to identify group differences within narrower diagnostic groups, and to examine predictive accuracy when logistic regression models were trained on one sample and tested on the other. With this confirmatory evidence in place, future studies should examine the utility of interceptive precision measures in predicting treatment outcomes and test whether these computational mechanisms might represent novel therapeutic targets.

Individuals with Methamphetamine Use Disorder Show Reduced Directed Exploration and Learning Rates Independent of an Aversive Interoceptive State Induction.

Methamphetamine Use Disorder (MUD) is associated with substantially reduced quality of life. Yet, decisions to use persist, due in part to avoidance of anticipated withdrawal states. However, the specific cognitive mechanisms underlying this decision process, and possible modulatory effects of aversive states, remain unclear. Here, 56 individuals with MUD and 58 healthy comparisons (HCs) performed a decision task, both with and without an aversive interoceptive state induction. Computational modeling measured the tendency to test beliefs about uncertain outcomes (directed exploration) and the ability to update beliefs in response to outcomes (learning rates). Compared to HCs, those with MUD exhibited less directed exploration and slower learning rates, but these differences were not affected by aversive state induction. These results suggest novel, state-independent computational mechanisms whereby individuals with MUD may have difficulties in testing beliefs about the tolerability of abstinence and in adjusting behavior in response to consequences of continued use.

The Changing Epidemiology of Traumatic Spine Injuries: A Trends Analysis of 26 Years of Patients at a Major Level 1 Trauma Center in the United States.

BACKGROUND CONTEXT: Traumatic spinal injuries (TSI) are associated with high morbidity, mortality, and resource utilization. The epidemiology of TSI varies greatly across different countries and regions and is impacted by national income levels, infrastructure, and cultural factors. Further, there may be changes over time. It is essential to investigate TSI to gain useful epidemiologic information. However, there have been no recent studies on trends for TSI in the US, despite the changing population demographics, healthcare policy, and technology. As a result, re-examination is warranted to reflect how the modern era has affected the epidemiology of US spine trauma patients and their management. PURPOSE: To determine epidemiologic trends in traumatic spine injuries over time. STUDY DESIGN/SETTING: Retrospective analysis; level 1 trauma center in the United States. PATIENT SAMPLE: A total of 21,811 patients, between the years of 1996 and 2022, who presented with traumatic spine injury. OUTCOME MEASURES: Age, sex, race, Injury Severity Score, mechanism of injury, injury diagnosis, injury level, rate of operative intervention, hospital length of stay, intensive care unit length of stay, discharge disposition, in-hospital mortality. METHODS: Data was collected from our institutional trauma registry over a 26-year period. Inclusion criteria involved at least one diagnosis of vertebral fracture, spinal cord injury, spinal subluxation, or intervertebral disc injury. Exclusion criteria consisted of patients with no diagnosed spine injury or a diagnosis of strain only. A total of 21,811 patients were included in the analysis. Descriptive statistics were tabulated and ordinary least squares linear regression was conducted for trends analysis. RESULTS: Regression analysis showed a significant upward trend in patient age (+13.83 years, ß=+0.65/year, p<0.001), female sex (+2.7%, ß=+0.18%/year, p=0.004), falls (+10.5%, ß=+0.82%/year, p<0.001), subluxations (+12.8%, ß=+0.35%/year, p<0.001), thoracic injuries (+1.5%, ß=+0.28%/year, p<0.001), and discharges to subacute rehab (+15.9%, ß=+0.68%/year, p<0.001). There was a significant downward trend in motor vehicle crashes (-7.8%, ß=-0.47%/year, p=0.016), firearms injuries (-3.4%, ß=-0.19%/year, p<0.001), sports/recreation injuries (-2.9%, ß=-0.18%/year, p<0.001), spinal cord injuries (-11.25%, ß=-0.37%, p<0.001), complete spinal cord injuries (-7.6%, ß=-0.24%/year, p<0.001), and discharges to home (+4.5%, ß=-0.27%/year, p=0.011). CONCLUSIONS: At our institution, the average spine trauma patient has trended toward older females. Falls represent an increasing proportion of the mechanism of injury, on a trajectory to become the most common cause. With time, there have been fewer spinal cord injuries and a lower proportion of complete injuries. At discharge, there has been a surge in the utilization of subacute rehabilitation facilities. Overall, there has been no significant change in injury severity, rate of operative intervention, length of stay, or mortality.

Psychological Resilience and Hardiness as Protective Factors in the Relationship Between Depression/Anxiety and Well-Being: Exploratory and Confirmatory Evidence.

Previous research shows depression and anxiety are negatively correlated with subjective well-being. Additionally, there is evidence psychological resilience positively influences well-being. The present study explored whether the relationship between depression/anxiety and subjective well-being might also be moderated by aspects of psychological resilience - such that depression and anxiety do not reduce well-being to the same extent in individuals high in psychological resilience traits. Participants from an exploratory sample (N = 236, Mage = 23.49) and confirmatory sample (N = 196, Mage = 24.99) completed self-report measures of depression, anxiety, well-being, resilience, and hardiness (i.e., CDRISC and DRS-15). As expected, results showed strong negative correlations between anxiety/depression and both well-being and resilience/hardiness, as well as positive correlations between well-being and resilience/hardiness. A significant interaction was also present between both resilience/hardiness and depression/anxiety in predicting well-being in the first sample. Results partially replicated in the confirmatory sample (i.e., for hardiness but not resilience). These findings add to prior work by highlighting hardiness (as measured by the DRS-15), one aspect of psychological resilience, as an important protective factor in mental health. Namely, results suggest individuals with symptoms of affective disorders may remain capable of living subjectively fulfilling lives if they possess traits of psychological resilience such as hardiness.

TNF signaling mediates cellular immune function and promotes malaria parasite killing in the mosquito Anopheles gambiae.

Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine and a master regulator of immune cell function in vertebrates. While previous studies have implicated TNF signaling in invertebrate immunity, the roles of TNF in mosquito innate immunity and vector competence have yet to be explored. Herein, we confirm the identification of a conserved TNF-α pathway in Anopheles gambiae consisting of the TNF-α ligand, Eiger, and its cognate receptors Wengen and Grindelwald. Through gene expression analysis, RNAi, and in vivo injection of recombinant TNF-α, we provide direct evidence for the requirement of TNF signaling in regulating mosquito immune cell function by promoting granulocyte midgut attachment, increased granulocyte abundance, and oenocytoid rupture. Moreover, our data demonstrate that TNF signaling is an integral component of anti-Plasmodium immunity that limits malaria parasite survival. Together, our data support the existence of a highly conserved TNF signaling pathway in mosquitoes that mediates cellular immunity and influences Plasmodium infection outcomes, offering potential new approaches to interfere with malaria transmission by targeting the mosquito host.

C-reactive protein concentrations diverge as a function of substance use disorder: A pre-registered replication in a clinical sample.

BACKGROUND: Inflammatory biomarkers may differentiate clinical disorders, which could lead to more targeted interventions. Analyses within a clinical sample (May et al., 2021) revealed that females with substance use disorders (SUD) exhibited lower C-reactive protein (CRP) and higher interleukin (IL)-8 and -10 concentrations than females without SUD who met criteria for mood/anxiety disorders. We aimed to replicate these findings in a new sample. METHODS: Hypotheses and analyses were preregistered. Treatment-seeking individuals with mood/anxiety disorders and/or SUD (N = 184) completed a blood draw, clinical interview, and questionnaires. Participants were categorized as SUD+ (45F, 43M) and SUD- (78F, 18M). Principal component analysis (PCA) of questionnaire data resulted in two factors reflecting appetitive and aversive emotional states. SUD group and nuisance covariates (PCA factors, age, body mass index [BMI], medication, nicotine [and hormones in females]) predicted biomarker concentrations (CRP, IL-8, and IL-10) in regressions. RESULTS: In females, the omnibus CRP model [F(8, 114) = 8.02, p <.001, R²-adjusted =.32] indicated that SUD+ exhibited lower CRP concentrations than SUD- (ß = -.33, t = -3.09, p =.002, 95% CI [-.54, -.12]) and greater BMI was associated with higher CRP levels (ß =.58, t = 7.17, p <.001, 95% CI [.42,.74]). SUD+ exhibited higher IL-8 levels than SUD- in simple but not omnibus regression models. CONCLUSION: Findings across two samples bolster confidence that females with SUD show attenuated CRP-indexed inflammation. As SUD+ comorbidity was high, replication is warranted with respect to specific SUD classes (i.e., stimulants versus cannabis).

Mild Hyperthermia Enhanced Liposomal Doxorubicin Delivery and CD8+ T cell Infiltration in Triple Negative Breast Cancer.

Mild hyperthermia (MHTh) is often used in combination with chemotherapy and radiotherapy for cancer treatment. In the current study, the effect of MHTh on the enhanced uptake of the FDA-approved chemotherapy drug, liposomal doxorubicin (dox) in syngeneic 4T1 tumors was investigated. Doxorubicin has inherent fluorescence properties having an emission signal at 590 nm upon excitation with a 480 nm laser. A group of mice administered with doxorubicin (dox) were exposed to MHTh (42 °C) for 30 minutes whereas control group given dox did not receive MHTh. Ex vivo optical imaging of harvested tumors confirmed higher uptake of dox in treated versus the control untreated tumors. Confocal microscopy of tumor sections indicates higher fluorescent intensity due to increased accumulation of dox in MHTh-treated compared to untreated tumors. We examined the effect of MHTh to enhance CD8 tumor infiltration, production of interferon-γ (IFN-γ) and expression of programmed death ligand-1 (PD-L1). mRNA in situ hybridization was performed to test for transcripts of CD8, IFN-γ and PD-L1. Results showed that higher expression of CD8 mRNA was observed in MHTh-administered tumors versus untreated cohorts. The signal for IFN-γ and PD-L1 in both groups were not significantly different. Taken together, our findings imply that MHTh can improve tumor uptake of dox. Importantly, our data suggests that MHTh can boost CD8+ T cell infiltration.

Quantifying the stochastic component of epigenetic aging.

DNA methylation clocks can accurately estimate chronological age and, to some extent, also biological age, yet the process by which age-associated DNA methylation (DNAm) changes are acquired appears to be quasi-stochastic, raising a fundamental question: how much of an epigenetic clock's predictive accuracy could be explained by a stochastic process of DNAm change? Here, using DNAm data from sorted immune cells, we build realistic simulation models, subsequently demonstrating in over 22,770 sorted and whole-blood samples from 25 independent cohorts that approximately 66-75% of the accuracy underpinning Horvath's clock could be driven by a stochastic process. This fraction increases to 90% for the more accurate Zhang's clock, but is lower (63%) for the PhenoAge clock, suggesting that biological aging is reflected by nonstochastic processes. Confirming this, we demonstrate that Horvath's age acceleration in males and PhenoAge's age acceleration in severe coronavirus disease 2019 cases and smokers are not driven by an increased rate of stochastic change but by nonstochastic processes. These results significantly deepen our understanding and interpretation of epigenetic clocks.

Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells.

Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting the synthesis of sphingosine 1-phosphate (S1P) by sphingosine kinase-2 and elevating dihydroceramides by inhibition of dihydroceramide desaturase. The present studies sought to determine the potential therapeutic activity of opaganib in cell culture and xenograft models of NB. Cytotoxicity assays demonstrated that NB cells, including cells with amplified MYCN, are effectively killed by opaganib concentrations well below those that accumulate in tumors in vivo. Opaganib was shown to cause dose-dependent decreases in S1P and hexosylceramide levels in Neuro-2a cells, while concurrently elevating levels of dihydroceramides. As with other tumor cells, opaganib reduced c-Myc and Mcl-1 protein levels in Neuro-2a cells, and also reduced the expression of the N-Myc protein. The in vivo growth of xenografts of human SK-N-(BE)2 cells with amplified MYCN was suppressed by oral administration of opaganib at doses that are well tolerated in mice. Combining opaganib with temozolomide plus irinotecan, considered the backbone for therapy of relapsed or refractory NB, resulted in increased antitumor activity in vivo compared with temozolomide plus irinotecan or opaganib alone. Mice did not lose additional weight when opaganib was combined with temozolomide plus irinotecan, indicating that the combination is well tolerated. Opaganib has additive antitumor activity toward Neuro-2a tumors when combined with the checkpoint inhibitor anti-CTLA-4 antibody; however, the combination of opaganib with anti-PD-1 or anti-PD-L1 antibodies did not provide increased antitumor activity over that seen with opaganib alone. Overall, the data demonstrate that opaganib modulates sphingolipid metabolism and intracellular signaling in NB cells and inhibits NB tumor growth alone and in combination with other anticancer drugs. Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody.

Effects of Hormonal Contraception and the Menstrual Cycle on Fatigability and Recovery From an Anaerobic Exercise Test.

ABSTRACT: Cabre, HE, Ladan, AN, Moore, SR, Joniak, KE, Blue, MNM, Pietrosimone, BG, Hackney, AC, and Smith-Ryan, AE. Effects of hormonal contraception and the menstrual cycle on fatigability and recovery from an anaerobic exercise test. J Strength Cond Res XX(X): 000-000, 2024-This study sought to evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared with a eumenorrheic (EUM) cycle, on fatigability and recovery between hormone the phases. Peak power (PP), average power (AP), fatigue index (FI), blood lactate, vessel diameter, and blood flow (BF) were measured from a repeated sprint cycle test (10 × 6 seconds) in 60, healthy, active women (mean ± SD; age: 26.5 ± 7.0 years, BMI: 22.5 ± 3.7 kg·m-2) who used monophasic OC (≥6 months; n = 21), had a H-IUD (≥6 months; n = 20), or had regular naturally occurring menstrual cycle (≥3 months) or had a nonhormonal IUD (EUM; n = 19). Subjects were randomly assigned to begin in either the low-hormone phase (LHP) or high-hormone phase (HHP) and were tested once in each phase. Separate univariate analyses of covariances assessed the change from HHP to LHP between the groups, covaried for progesterone, with significance set at p ≤ 0.05. All groups demonstrated similar changes in PP, AP, FI, blood lactate, vessel diameter, and BF between the phases (p > 0.05). Although not significant, AP was higher in LHP for OC (Δ -248.2 ± 1,301.4 W) and EUM (Δ -19.5 ± 977.7 W) and higher in HHP for H-IUD (Δ 369.3 ± 1,123.0 W). Oral contraceptive group exhibited a higher FI (Δ 2.0%) and reduced blood lactate clearance (Δ 2.5%) in HHP. In recreationally active women, hormonal contraception and hormone phases may minimally impact fatigue and recovery. Individual elite female athletes may benefit from understanding hormonal contraception type as performance and recovery may slightly vary across the cycle.

Longitudinal Assessment of Emergency Responders' Attitudes Toward People Who Overdose and Naloxone Following an Overdose Education Training.

BACKGROUND: In addition to teaching overdose recognition and response, overdose education and naloxone distribution (OEND) trainings for emergency responders aim to improve trainee attitudes toward people who use drugs and toward naloxone. This study examines the training effectiveness long term, as well as the extent to which improvements are dependent on profession type or recent experience administering naloxone. METHODS: A total of 774 emergency responders, consisting of law enforcement officers (LEOs) (n = 624, 81%) and emergency medical service (EMS) personnel (n = 150, 19%), attended OEND trainings and completed surveys immediately prior to ("pre") and following ("post") the training, as well as 6 months later ("follow-up"). Survey items assessed attitudes toward people who have overdosed, naloxone-related risk compensation (ie, "enabling") beliefs, and whether participants had administered naloxone since attending the training. Multiple regression and estimated marginal means were used to evaluate changes in scores. RESULTS: Emergency responders showed improved attitudes (pre = 2.60, follow-up = 2.45, P < .001) and risk compensation beliefs (pre = 2.97, follow-up = 2.67, P < .001) 6 months following the training. Follow-up scores differed by profession, with LEOs endorsing worse attitudes (difference = 0.55, P = .013) and more risk compensation beliefs (difference = 0.67, P = .014) than EMS. In addition, having recently administered naloxone predicted more negative attitudes (EMS: difference = 0.55, P = .01; LEO: difference = 0.54, P = .004) and risk compensation beliefs (EMS = 0.73, P = .006; LEO = 0.69, P = .002) at follow-up. CONCLUSION: Six months after an OEND training, emergency responders' attitudes toward people who overdose, and their risk compensation beliefs remained improved. However, LEOs had more negative follow-up attitudes and beliefs compared to EMS. Emergency responders who had administered naloxone had worse attitudes and beliefs at follow-up than those who had not. Of note, our sample evidenced sizable attrition between pre and follow-up assessments, leaving room for selection bias. Future studies should investigate how to mitigate negative effects of administering naloxone on attitudes toward those who overdose, and belief that naloxone is "enabling."

Unconscious activation of negative emotional memories increases pain unpleasantness.

OBJECTIVE: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall). METHODS: 72 healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral & 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial. RESULTS: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative vs. neutral images (5.52 [SD = 2.06] vs. 5.23 [SD = 2.10]; p = 0.02). This pattern was also present when comparing cues to remembered negative vs. neutral images (5.62 [SD = 1.94] vs. 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative vs. neutral images when remembered (5.48 [SD = 1.79] vs. 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] vs. 5.16 [SD = 1.93]; p = 0.30). CONCLUSIONS: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to non-recallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions.

Stripping versus ligation of vas deferens in microscopic denervation of spermatic cord in men with chronic orchialgia: A multicenter study.

BACKGROUND: Microdenervation of the spermatic cord (MSCD) is an effective treatment modality for men with intractable scrotal content pain. For patients not interested in preserving fertility, some centers advocate ligation of the vas during denervation, while others prefer stripping of the vas deferens to preserve the vasal artery, hence preserving vasculature to the testis and possibly decreasing post-operative congestion pain. OBJECTIVE: To compare outcomes of patients with chronic orchialgia, who underwent MSCD by either stripping or ligating the vas deferens. MATERIALS AND METHODS: A retrospective chart review of 85 patients who underwent MSCD from 2017-2023 was performed. Patients' demographics including history of prior surgical procedures were recorded. Response to surgery was evaluated as either complete resolution of pain, partial resolution of pain, or no improvement in pain. RESULTS: Eighty-five patients underwent MSCD with a median (interquartile range, IQR) age of 36 (25.5-46.5) years and median duration of pain of 16 (6-31) months. Thirty-seven patients underwent stripping of vas, while 48 underwent ligation of vas during MSCD. Median follow up was 12 months. Twenty-one (43.5%) patients had prior inguinal scrotal surgery in the ligation group compared to 5 (13.5%) in the stripping group, p = 0.003. The etiology of pain was similar between the groups. The response to MSCD between the two groups was similar, 67.6% of patients who underwent stripping had complete resolution of pain versus 66.7% of those who had ligation (p = 0.968), with similar rates of post-operative complications (p-value = 0.132). CONCLUSIONS: In men with intractable chronic scrotal content pain with no interest in preserving fertility, ligation, or stripping of the vas deferens yields similar outcomes with regard to pain resolution. Both techniques are safe with no reports of any testicular atrophy.

Not all mindfulness is equal: certain facets of mindfulness have important implications for well-being and mental health across the lifespan.

The connections between the five facets of mindfulness, well-being, and mental health across the lifespan have traditionally been investigated using variable-centered approaches. Less research has investigated these relationships from a person-centered, profile-based approach. In this work, we aimed to identify the profiles of mindfulness in a Canadian lifespan sample (14 to 90 years of age) and investigate how these profiles compared on age, well-being, and mental health. An age- and gender-balanced sample of 1,600 participants completed a questionnaire that measured the five facets of mindfulness; life satisfaction; existential well-being; and anxiety, depression, and stress symptoms. A latent profile analysis was conducted. Five profiles based on the five-facet model of mindfulness were identified: high mindfulness, moderate mindfulness, low mindfulness, nonjudgmentally aware, and judgmentally observing. The 3-step approach to profile comparisons was used to assess age, mental health, and well-being differences across the profiles. Those in the high mindfulness and nonjudgmentally aware profiles were generally older, while the judgmentally observing profile contained younger individuals. Those in the high mindfulness and nonjudgmentally aware profiles reported the greatest mental health and well-being. Conversely, those in the low mindfulness and judgmentally observing profiles had worse mental health than the other profiles. The moderate mindfulness profile was situated between these profile groups on age, mental health, and well-being outcomes. This pattern of results has implications for mindfulness-based intervention research and practice to better account for heterogeneity in mindfulness and better support well-being across the lifespan.

Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study.

BACKGROUND: Despite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients' and physicians' real-world experiences with eptinezumab for chronic migraine (CM). METHODS: REVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience. RESULTS: Of the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported "good" days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses. CONCLUSION: This real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians.

Delays in blood collection and drug toxicology results among crash-involved drivers arrested for impaired driving.

OBJECTIVE: The concentration of drugs in a driver's system can change between an impaired driving arrest or crash and the collection of a biological specimen for drug testing. Accordingly, delays in specimen collection can result in the loss of critical information that has the potential to affect impaired driving prosecution. The objectives of the study were: (1) to identify factors that influence the time between impaired-driving violations and specimen collections (time-to-collection) among crash-involved drivers, and (2) to consider how such delays affect measured concentrations of drugs, particularly with respect to common drug per se limits. METHOD: Study data included blood toxicology results and crash-related information from 8,923 drivers who were involved in crashes and arrested for impaired driving in Wisconsin between 2019 and 2021. Analyses examined how crash timing and severity influenced time-to-collection and the effects of delays in specimen collection on blood alcohol concentrations (BACs) and blood delta-9-tetrahydrocannabinol (THC) concentrations. RESULTS: The mean time-to-collection for the entire sample was 1.80 h. Crash severity had a significant effect on time-to-collection with crashes involving a fatality having the longest duration (M = 2.35 h) followed by injury crashes (M = 2.06 h) and noninjury crashes (M = 1.69 h). Time of day also affected time-to-collection; late night and early morning hours were associated with shorter durations. Both BAC (r = -0.11) and blood THC concentrations (r = -0.16) were significantly negatively correlated with time-to-collection. CONCLUSIONS: Crash severity and the time of day at which a crash occurs can result in delays in the collection of blood specimens after impaired driving arrests. Because drugs often continue to be metabolized and eliminated between arrest and biological specimen collection, measured concentrations may not represent the concentrations of drugs that were present at the time of driving. This has the potential to affect drug-impaired driving prosecution, particularly in jurisdictions whose laws specify per se impairment thresholds.

Mosquito immune cells enhance dengue and Zika virus dissemination in Aedes aegypti.

Mosquito-borne viruses cause more than 400 million annual infections and place over half of the world's population at risk. Despite this importance, the mechanisms by which arboviruses infect the mosquito host and disseminate to tissues required for transmission are not well understood. Here, we provide evidence that mosquito immune cells, known as hemocytes, play an integral role in the dissemination of dengue virus (DENV) and Zika virus (ZIKV) in the mosquito Aedes aegypti. We establish that phagocytic hemocytes are a focal point for virus infection and demonstrate that these immune cell populations facilitate virus dissemination to the ovaries and salivary glands. Additional transfer experiments confirm that virus-infected hemocytes confer a virus infection to non-infected mosquitoes more efficiently than free virus in acellular hemolymph, revealing that hemocytes are an important tropism to enhance virus dissemination in the mosquito host. These data support a "trojan horse" model of virus dissemination where infected hemocytes transport virus through the hemolymph to deliver virus to mosquito tissues required for transmission and parallels vertebrate systems where immune cell populations promote virus dissemination to secondary sites of infection. In summary, this study significantly advances our understanding of virus infection dynamics in mosquitoes and highlights conserved roles of immune cells in virus dissemination across vertebrate and invertebrate systems.

Body composition, physical activity, and menopause symptoms: how do they relate?

OBJECTIVE: This study characterized the impact of physical activity (light, moderate, and vigorous [VIG] active minutes per day) and body composition (percent body fat [%BF] and fat-free mass index) on total menopausal symptoms (TMSs) in 72 premenopausal, perimenopausal (PERI), or postmenopausal women. METHODS: Activity minutes were collected from wearable fitness trackers. Body composition was evaluated using a whole-body dual-energy x-ray absorptiometry scan. TMSs were quantified using The North American Menopause Society Questionnaire. RESULTS: Significant associations were observed between TMSs and %BF ( r = 0.464, P < 0.001) and VIG ( r = -0.245, P = 0.038). %BF and VIG were significant predictors for TMSs across groups ( R2 = 0.146 and R2 = 0.092, respectively), but only %BF maintained for PERI ( R2 = 0.421, P < 0.001). CONCLUSIONS: %BF predicted nearly half of the variance in PERI TMSs, whereas VIG predicted 9% of the sample variance, demonstrating an important influence of body fat accumulation and intense physical activity in the menopause transition. High-intensity exercise interventions to alleviate body composition changes may also reduce menopausal-related symptoms for PERI women.