Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types.

Inhibition of the bromodomain and extraterminal domain (BET) protein family is a potential strategy to prevent and treat diabetes; however, the clinical use of BET bromodomain inhibitors (BETi) is associated with adverse effects. Here, we explore a strategy for targeting BETi to ß-cells by exploiting the high zinc (Zn2+) concentration in ß-cells relative to other cell types. We report the synthesis of a novel, Zn2+-chelating derivative of the pan-BETi (+)-JQ1, (+)-JQ1-DPA, in which (+)-JQ1 was conjugated to dipicolyl amine (DPA). As controls, we synthesized (+)-JQ1-DBA, a non-Zn2+-chelating derivative, and (-)-JQ1-DPA, an inactive enantiomer that chelates Zn2+. Molecular modeling and biophysical assays showed that (+)-JQ1-DPA and (+)-JQ1-DBA retain potent binding to BET bromodomains in vitro. Cellular assays demonstrated (+)-JQ1-DPA attenuated NF-ĸB target gene expression in ß-cells stimulated with the pro-inflammatory cytokine interleukin 1ß. To assess ß-cell selectivity, we isolated islets from a mouse model that expresses green fluorescent protein in insulin-positive ß-cells and mTomato in insulin-negative cells (non-ß-cells). Surprisingly, Zn2+-chelation did not confer ß-cell selectivity as (+)-JQ1-DPA was equally effective in both ß- and α-cells; however, (+)-JQ1-DPA was less effective in macrophages, a non-endocrine islet cell type. Intriguingly, the non-Zn2+-chelating derivative (+)-JQ1-DBA displayed the opposite selectivity, with greater effect in macrophages compared to (+)-JQ1-DPA, suggesting potential as a macrophage-targeting molecule. These findings suggest that Zn2+-chelating small molecules confer endocrine cell selectivity rather than ß-cell selectivity in pancreatic islets and provide valuable insights and techniques to assess Zn2+-chelation as an approach to selectively target small molecules to pancreatic ß-cells.

Patient and public involvement and engagement (PPIE): how valuable and how hard? An evaluation of ALL_EARS@UoS PPIE group, 18 months on.

BACKGROUND: ALL_EARS@UoS is a patient and public involvement and engagement (PPIE) group for people with lived experience of hearing loss. The purpose of the group is to share experiences of hearing loss and hearing healthcare, inform research and improve services for patients at University of Southampton Auditory Implant Service. A year after inception, we wanted to critically reflect on the value and challenges of the group. Four members of ALL_EARS@UoS were recruited to an evaluation steering group. This paper reports the evaluation of the group using the UK Standards for Public Involvement. METHODS: An anonymous, mixed-methods questionnaire was co-designed and shared with members of ALL_EARS@UoS using an online platform. The questionnaire was designed to capture satisfaction, individual feedback through free-text answers, and demographic information. Descriptive statistics have been used to express the satisfaction and demographic data. Reflexive thematic analysis has been used to analyse the free-text responses. Group engagement and activity data over time were monitored and collected. RESULTS: The questionnaire response rate was 61% (11/18). Areas identified as strengths were 'Communication' and 'Working together'. Five themes were developed from the thematic analysis; (1) Increased knowledge and awareness around the topic of hearing health for group members and wider society, (2) supporting research, (3) inclusivity within the group, (4) opportunity to make a difference for people in the future and (5) running of the group/group organisation. The data highlighted the value and challenges of PPIE. Members described feeling listened to and appreciation of being able to share experiences. Time of day and meeting format were identified as challenges as they affected who could attend the meetings. The ability to secure and maintain sufficient funding and time to support inclusive and diverse PPIE activities is a challenge for researchers. CONCLUSIONS: We have identified how PPIE added value to both group members and researchers, emphasising the true benefit of PPIE. We have highlighted challenges we are facing and our plan to tackle these. We aim to continue to develop and sustain a group that reflects the diversity of the Deaf/deaf or hard of hearing community and of our local community.

Impact of the COVID-19 pandemic on mental health and viral suppression among persons living with HIV in western Washington.

The COVID-19 pandemic and social distancing measures elevated stress levels globally, exacerbating mental health challenges for people with HIV (PWH). We examined the effect of COVID-19-related stress on mental health among PWH in western Washington, exploring whether social support and coping self-efficacy were protective. Data on COVID-19-related stress, mental health, social support, and coping self-efficacy were collected using online surveys during the pandemic. Pre-COVID-19 mental health data were available for a subset of participants and were linked with the survey data. In the total sample (N = 373), COVID-19-stress was associated with elevated depression (PHQ-8, ß = 0.21, 95%CI [0.10, 0.32]) and anxiety (GAD-7, ß = 0.28, 95%CI [0.17, 0.39]). Among the subset of respondents with pre-pandemic mental health data (N = 103), COVID-19-related stress was associated with elevated PHQ-8 scores (ß = 0.35, 95%CI [0.15, 0.56]) and GAD-7 scores (ß = 0.35, 95%CI [0.16, 0.54]), adjusted for baseline mental health and other confounders. Coping self-efficacy was negatively associated with GAD-7 scores (ß = -0.01, 95%CI [-0.01, 0.00]), while social support was negatively associated with PHQ-8 scores (ß = -0.06, 95%CI [-0.12, -0.01]). Viral suppression before and during the pandemic did not differ among participants with available data. While COVID-19-related stress predicted elevated depression and anxiety symptoms among PWH, social support and coping self-efficacy were protective.

Effects of cannabidiol and Δ9-tetrahydrocannabinol on cytochrome P450 enzymes: a systematic review.

Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included 'cannabidiol', 'tetrahydrocannabinol', and 'cytochrome P450'. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included. Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, cause changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.

Gaze and behavioural metrics in the refractive correction of presbyopia.

PURPOSE: To investigate gaze and behavioural metrics at different viewing distances with multifocal contact lenses (MFCLs), single vision contact lenses (SVCLs) and progressive addition lenses (PALs). METHODS: Fifteen presbyopic contact lens wearers participated over five separate study visits. At each visit, participants were randomly assigned to wear one of five refractive corrections: habitual PAL spectacles, delefilcon A (Alcon Inc.) MFCLs and three separate pairs of delefilcon A single vision lenses worn as distance, intermediate and near corrections. Participants wore a Pupil Core headset to record eye and head movements while performing three visual tasks: reading, visual search and scene observation. Data were investigated using linear regression and post-hoc testing. Parameters of interest included gaze (fixation duration, head movement) and behavioural (reading speed, reading accuracy, visual search time) metrics. RESULTS: Reading speed in SVCLs was significantly faster than in MFCLs and PAL spectacles (F = 16.3, p < 0.0001). Refractive correction worn did not influence visual search times (F = 0.16, p = 0.85). Fixation duration was significantly affected by the type of visual task (F = 60.2, p < 0.001), and an interaction effect was observed between viewing distance and refractive correction (F = 4.3, p = 0.002). There was significantly more horizontal and vertical head movement (F = 3.2, p = 0.01 and F = 3.3, p = 0.01, respectively) during visual search tasks when wearing PAL spectacles compared to SVCLs or MFCLs. CONCLUSION: This work showed that the type of refractive correction affects behavioural metrics such as reading speed and gaze behaviour by affecting horizontal and vertical head movements. The findings of this study suggest that under certain conditions, wearers of MFCLs make fewer head movements compared to PAL spectacles. Gaze behaviour metrics offer a new approach to compare and understand contact lens and spectacle performance, with potential applications including peripheral optical designs for myopia management.

Impact of the COVID-19 Pandemic on Persons Living with HIV in Western Washington: Examining Lived Experiences of Social Distancing Stress, Personal Buffers, and Mental Health.

Pandemic-related stressors may disproportionately affect the mental health of people with HIV (PWH). Stratified, purposive sampling was used to recruit 24 PWH who participated in a quantitative survey on COVID-19 experiences for in-depth interviews (IDIs). IDIs were conducted by Zoom, audio recorded and transcribed. Thematic analysis was used to develop an adapted stress-coping model. Participants experienced acute stress following exposure events and symptoms compatible with COVID-19. Social isolation and job loss were longer-term stressors. While adaptive coping strategies helped promote mental health, participants who experienced multiple stressors simultaneously often felt overwhelmed and engaged in maladaptive coping behaviors. Healthcare providers were important sources of social support and provided continuity in care and referrals to mental health and social services. Understanding how PWH experienced stressors and coped during the COVID-19 pandemic can help healthcare providers connect with patients during future public health emergencies, address mental health needs and support adaptive coping strategies.

End-of-day assessment of asymptomatic versus highly symptomatic soft contact lens wearers.

PURPOSE: To investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear. METHODS: In this pilot investigation, Phase 1 identified asymptomatic (CLDEQ-8 score ≤ 7) and highly symptomatic (CLDEQ-8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL-wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post-hoc testing. The relationship between comfort scores and the clinical parameters was also investigated. RESULTS: Overall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty-five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference -0.04 mm, 95% CI: -0.07, -0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference -9.89, 95% CI: -18.91, -0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = -0.40, 95% CI: -0.63, -0.11) and blink rate (r = -0.31, 95% CI: -0.57, -0.003). CONCLUSION: The potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining.

Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression.

AIMS: Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States. MATERIALS AND METHODS: Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18). RESULTS: Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible. LIMITATIONS: Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results. CONCLUSIONS: Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

A new widely distributed invasive alien species of Amasa ambrosia beetles (Coleoptera: Curculionidae: Scolytinae: Xyleborini).

Amasa parviseta Knek & Smith, new species is described from Australia, Brazil, Uruguay, France and Spain. The species is native to Australia and appears to have spread widely in association with introduced Eucalyptus species.

Behavioural activation to mitigate the psychological impacts of COVID-19 restrictions on older people in England and Wales (BASIL+): a pragmatic randomised controlled trial.

BACKGROUND: Older adults were more likely to be socially isolated during the COVID-19 pandemic, with increased risk of depression and loneliness. We aimed to investigate whether a behavioural activation intervention delivered via telephone could mitigate depression and loneliness in at-risk older people during the COVID-19 pandemic. METHODS: BASIL+ (Behavioural Activation in Social Isolation) was a pragmatic randomised controlled trial conducted among patients recruited from general practices in England and Wales, and was designed to assess the effectiveness of behavioural activation in mitigating depression and loneliness among older people during the COVID-19 pandemic. Eligible participants were aged 65 years and older, socially isolated, with a score of 5 or higher on the Patient Health Questionnaire-9 (PHQ-9), and had multiple long-term conditions. Participants were allocated in a 1:1 ratio to the intervention (behavioural activation) or control groups by use of simple randomisation without stratification. Behavioural activation was delivered by telephone; participants were offered up to eight weekly sessions with trained BASIL+ Support Workers. Behavioural activation was adapted to maintain social connections and encourage socially reinforcing activities. Participants in the control group received usual care with existing COVID-19 wellbeing resources. The primary clinical outcome was self-reported depression severity, assessed by the PHQ-9, at 3 months. Outcomes were assessed masked to allocation and analysis was by treatment allocation. This trial is registered with the ISRCTN registry (ISRCTN63034289). FINDINGS: Between Feb 8, 2021, and Feb 28, 2022, 449 eligible participants were identified and 435 from 26 general practices were recruited and randomly assigned (1:1) to the behavioural activation intervention (n=218) or to the control group (usual care with signposting; n=217). The mean age of participants was 75·7 years (SD 6·7); 270 (62·1%) of 435 participants were female, and 418 (96·1%) were White. Participants in the intervention group attended an average of 5·2 (SD 2·9) of eight remote behavioural activation sessions. The adjusted mean difference in PHQ-9 scores between the control and intervention groups at 3 months was -1·65 (95% CI -2·54 to -0·75, p=0·0003). No adverse events were reported that were attributable to the behavioural activation intervention. INTERPRETATION: Behavioural activation is an effective and potentially scalable intervention that can reduce symptoms of depression and emotional loneliness in at-risk groups in the short term. The findings of this trial add to the range of strategies to improve the mental health of older adults with multiple long-term conditions. These results can be helpful to policy makers beyond the pandemic in reducing the global burden of depression and addressing the health impacts of loneliness, particularly in at-risk groups. FUNDING: UK National Institute for Health and Care Research.

Identification of Protein Targets of S-Nitroso-Coenzyme A-Mediated S-Nitrosation Using Chemoproteomics.

S-Nitrosation is a cysteine post-translational modification fundamental to cellular signaling. This modification regulates protein function in numerous biological processes in the nervous, cardiovascular, and immune systems. Small molecule or protein nitrosothiols act as mediators of NO signaling by transferring the NO group (formally NO+) to a free thiol on a target protein through a transnitrosation reaction. The protein targets of specific transnitrosating agents and the extent and functional effects of S-nitrosation on these target proteins have been poorly characterized. S-nitroso-coenzyme A (CoA-SNO) was recently identified as a mediator of endogenous S-nitrosation. Here, we identified direct protein targets of CoA-SNO-mediated transnitrosation using a competitive chemical-proteomic approach that quantified the extent of modification on 789 cysteine residues in response to CoA-SNO. A subset of cysteines displayed high susceptibility to modification by CoA-SNO, including previously uncharacterized sites of S-nitrosation. We further validated and functionally characterized the functional effects of S-nitrosation on the protein targets phosphofructokinase (platelet type), ATP citrate synthase, and ornithine aminotransferase.

Defining a core configuration for human centromeres during mitosis.

The centromere components cohesin, CENP-A, and centromeric DNA are essential for biorientation of sister chromatids on the mitotic spindle and accurate sister chromatid segregation. Insight into the 3D organization of centromere components would help resolve how centromeres function on the mitotic spindle. We use ChIP-seq and super-resolution microscopy with single particle averaging to examine the geometry of essential centromeric components on human chromosomes. Both modalities suggest cohesin is enriched at pericentromeric DNA. CENP-A localizes to a subset of the α-satellite DNA, with clusters separated by ~562 nm and a perpendicular intervening ~190 nM wide axis of cohesin in metaphase chromosomes. Differently sized α-satellite arrays achieve a similar core structure. Here we present a working model for a common core configuration of essential centromeric components that includes CENP-A nucleosomes, α-satellite DNA and pericentromeric cohesion. This configuration helps reconcile how centromeres function and serves as a foundation to add components of the chromosome segregation machinery.

Fusarium kuroshium is the primary fungal symbiont of an ambrosia beetle, Euwallacea fornicatus, and can kill mango tree in Japan.

This study identifies fungi associated with Euwallacea fornicatus and determines whether these fungal species play the role of primary symbiont. E. fornicatus adults that emerged from the branches of infested trees in Okinawa main island, Japan, were collected and used to isolate fungi. Fusarium kuroshium and Penicillium citrinum were the most dominant fungal associates of females and males, respectively. F. kuroshium was much more frequently isolated from the head, including mycangia (fungus-carrying organs), of females than any other body parts. We inoculated healthy mango saplings with F. kuroshium or F. decemcellulare, both of which were symbionts of E. fornicatus females infesting mango trees. F. kuroshium decreased leaf stomatal conductance and rate of xylem sap-conduction area and increased length and area of xylem discoloration of the saplings, thereby weakening and killing some. These results suggest that F. kuroshium, a mycangial fungus of E. fornicatus, inhibits water flow in mango trees. This study is the first to report that F. kuroshium causes wilt disease in mango trees and that it is a primary fungal symbiont of E. fornicatus.

Pediatric Patients Hospitalized With Eating Disorders in Ontario, Canada, Over Time.

Importance: Understanding the evolving characteristics of pediatric patients hospitalized for eating disorders is important to ensure that services and treatments align with patient needs. Objective: To examine temporal trends in the rates of hospitalizations for pediatric eating disorders by clinical and demographic characteristics in Ontario, Canada, over a 17-year period. Design, Setting, and Participants: This population-based, repeated, cross-sectional study used linked health administrative and demographic databases in Ontario, Canada, to identify individuals aged 5 to 17 years hospitalized with eating disorder diagnoses from April 1, 2002, to March 31, 2020. Data analyses were performed from May 2021 to June 2023. Exposure: Fiscal year (April 1-March 31) of eating disorder hospitalization. Main Outcomes and Measures: Outcomes of interest were absolute and relative changes in pediatric eating disorder hospitalization rates overall and stratified by patient sex, age groups, and eating disorder diagnostic groups. Results: Over the study period, there were 11 654 pediatric eating disorder hospitalizations, of which 5268 (45.2%) were for anorexia nervosa and 1374 (11.8%) were for bulimia nervosa. There were a total of 10 648 hospitalizations (91.4%) among female patients, and the median (IQR) age was 15.0 (14-0-16.0) years. Hospitalization rates increased 139% from 2002 to 2019, from 2.0 per 10 000 population to 4.8 per 10 000 population. The largest relative changes were observed among male patients (416%; from 0.2 per 10 000 population to 1.1 per 10 000 population), individuals aged 12 to 14 years (196%; from 2.2 per 10 000 population to 6.6 per 10 000 population), and individuals with eating disorders other than anorexia or bulimia nervosa (255%; from 0.6 per 10 000 population to 2.1 per 10 000 population). Male patients, younger adolescents, and individuals with other eating disorders also represented larger proportions of hospitalizations by fiscal 2019. Conclusions and Relevance: In this cross-sectional study of eating disorder hospitalizations, pediatric hospitalizations increased over time, particularly among populations traditionally considered atypical. Existing eating disorder programs must adapt to accommodate changing patient presentations and increased volumes to ensure effective care delivery.

Anticipatory and consummatory pleasure in avoidant/restrictive food intake disorder.

BACKGROUND: Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment. METHODS: A sample of 71 participants ages 10-23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed. RESULTS: The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed. CONCLUSIONS: These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms.

Individuals with eating disorders often report elevated anhedonia, or an inability to experience pleasure. Past research on pleasure in eating disorders has focused primarily on individuals with anorexia nervosa and bulimia nervosa, and it is unclear whether people with other eating disorders also experience lower pleasure than healthy individuals. In the current study, we measured anticipatory pleasure (looking forward to something enjoyable) and consummatory pleasure (enjoying a pleasant stimulus) in a sample with avoidant/restrictive food intake disorder (ARFID) and healthy controls. We also repeated our analyses after removing food-related items from the scale assessing pleasure. The ARFID group scored lower on both dimensions of pleasure than controls, but this difference was primarily due to greater depression symptoms and the presence of food-related items in the pleasure questionnaire. Within the ARFID sample, individuals with more severe ARFID reported less anticipatory pleasure, even after removing questions about enjoyment of food. Lower anticipatory pleasure was especially characteristic of the lack of interest in eating phenotype of ARFID. These results suggest that ARFID severity, lack of interest in eating, and depression contribute to low pleasure in this population.

Bradycardic Arrest in a Child with Complex Congenital Heart Disease Due to Sugammadex Administration.

The neuromuscular blocking drugs rocuronium and vecuronium are often used during general anesthesia. These drugs temporarily paralyze the patient and thus both facilitate placement of an endotracheal tube and prevent any patient movement during surgery. Reversal of neuromuscular blockade is necessary at the end of surgery to avoid postoperative weakness and adverse respiratory events in the recovery room. Neostigmine, the traditional reversal agent, may not completely restore muscle strength. Sugammadex is a reversal agent that is more effective and quicker acting than neostigmine. In adults, sugammadex administration has rarely been associated with bradycardia and cardiac arrest. In healthy children, the bradycardia that occurs after sugammadex administration is benign and does not require intervention. There is 1 case report of a 10- to 15-second bradycardic arrest after sugammadex administration to a 10-year-old child with heart disease. The present case report describes an 8-month-old child with complex congenital heart disease who experienced a 10-minute bradycardic arrest after the administration of sugammadex. Pediatric anesthesiologists should be aware that sugammadex administration to children with heart disease may cause hemodynamically significant bradycardia.