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Background: One-way alphanumeric pagers remain a primary communication method for health care providers, despite the rise of app-based communication systems. Frequent nonurgent pages can disrupt workflows and potentially impact patient care, particularly in high-demand specialties like Oral and Maxillofacial Surgery (OMS)., Purpose: The purpose of this study was to examine the association between paging patterns and time of day among OMS residents., Study Design, Setting, Sample: This retrospective cohort study analyzed paging data from the Emory Healthcare OMS service in 2021 and 2022. Pages included were those received by primary OMS residents responsible for inpatient care, consultations, and emergency department evaluations. Exclusions were pages related to outpatient matters and those sent to backup or senior-level residents., Predictor Variable: The primary predictor variable was paging rate, defined as the number of pages received per hour. This measure captures the intensity of paging activity during specific periods., Main Outcome Variable: The primary outcome variable was time of day, categorized into peak and off-peak hours. Peak hours were statistically determined through data analysis and were defined as 07:00-20:00 on weekdays and 09:00-14:00 on weekends. Off-peak hours included all other time periods. Secondary outcomes included the comparison of paging rates on weekdays versus weekends to identify potential variations in paging activity., Covariates: There are no covariates., Results: There were 7,224 pages. Of them, 4,626 pages met the inclusion criteria. In 2021, there was an average of 18.8 pages per day (range: 0 to 56; SD: 10.2). In 2022, there were 19.2 pages per day (range: 3 to 52; SD: 8.7). Weekdays had more pages (20.8 pages/day) than weekends (14.3 pages/day; P < .001). During weekday peak hours, there were 1.3 pages/hour compared to 0.4 pages/hour during off peak hours (P < .001). During weekend peak hours, there were 0.9 pages/hour compared to 0.5 pages/hour during off-peak hours (P value < .001). Weekdays between 0700 and 0800 had the highest average number of pages (1.53 pages/hour)., Conclusion and Relevance: This study identified patterns in paging rates, with significantly higher paging activity during peak hours and on weekdays. Awareness of these patterns may inform the development of protocols to minimize nonurgent interruptions during critical times, such as during patient handoffs., (Copyright © 2024. Published by Elsevier Inc.)

Musculoskeletal injury (MSKi), depression, anxiety and burnout place a considerable burden on emergency services personnel and healthcare providers (HCP). Physical fitness is related to both mental and physical health in these populations but females in these are hugely underrepresented in this literature. As female representation in first-responder and HCP roles increases, the need for female specific research is needed. This study examines physical fitness as a short-term indicator of future reproductive health, MSKi, and mental health for females employed as first-responders or HCP. Thirteen first-responders and 29 HCP completed an initial health and demographics questionnaire, a comprehensive physical assessment (e.g., bone mineral density, muscular strength, muscular endurance, muscular power, flexibility, and aerobic capacity), and a health questionnaire 6-7 months after the physical testing. We found that i) bone mineral density, relative upper body strength, and lowerbody power were related to sustaining future MSKi, ii) better lower body endurance and flexibility was related to future menstrual cycle disruptions, and iii) low bone mineral density was related future self-reported burnout and Patient Health Questionnaire score >10. Physical fitness characteristics can be helpful indicators of future MSKi risk, menstrual cycle disruptions, and mental health status in females employed in arduous occupations.

Alcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment. We developed LIQ PARTI (Lick Instance Quantifier with Poly-Animal RFID Tracking Integration), an open-source tool to examine home cage continuous access two-bottle choice drinking behavior in a group-housed setting, investigating the influence of sex and social isolation on ethanol consumption and bout microstructure in C57Bl/6J mice. LIQ PARTI, based on our previously developed single-housed LIQ HD system, accurately tracks drinking behavior using capacitive-based sensors and RFID technology. Group-housed female mice exhibited higher ethanol preference than males, while males displayed a unique undulating pattern of ethanol preference linked to cage changes, suggesting a potential stress or novelty-related response. Chronic ethanol intake distinctly altered bout microstructure between male and female mice, highlighting sex and social environmental influences on drinking behavior. Social isolation with the LIQ HD system amplified fluid intake and ethanol preference in both sexes, accompanied by sex- and fluid-dependent changes in bout microstructure. However, these effects largely reversed upon resocialization, indicating the plasticity of these behaviors in response to social context. Utilizing a novel group-housed home cage lickometer device, our findings illustrate the critical interplay of sex and housing conditions in voluntary alcohol drinking behaviors in C57Bl/6J mice, facilitating nuanced insights into the potential contributions to AUD etiology., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Petersen et al.)

Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. These new findings support the view that gut vagal afferents and the cNTS NA -to-vlBNST circuit play a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior., (© 2024 Wiley Periodicals LLC.)

Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3 + T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models. Despite the broad expression of CD38 across human tissues, ISB 2001 demonstrated a reduced T cell activation profile in the absence of tumor cells when compared to TCEs targeting CD38 only. To determine an optimal first-in-human dose for the ongoing clinical trial ( NCT05862012 ), we developed an innovative quantitative systems pharmacology model leveraging preclinical data, using a minimum pharmacologically active dose approach, therefore reducing patient exposure to subefficacious doses of therapies., (© 2024. The Author(s).)

This report describes a case of retinal vasculitis in a patient with autoimmune lymphoproliferative syndrome (ALPS). A 13-year-old girl undergoing work-up for immune dysregulation was referred for retinal vasculitis. The patient was asymptomatic on presentation, but her retinal examination was remarkable for areas of outer retinal and choriocapillary loss and focal vascular inflammation. Subsequent bone marrow biopsy with genetic sequencing revealed a diagnosis of ALPS, and she was started on immunosuppression. Most cases of ocular ALPS have anterior involvement, but retinal changes may rarely occur in isolation. Patients with ALPS may benefit from routine eye examination and monitoring. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.] .

This study aims to examine the validity and reliability of the UltraScan650™, a portable ultrasound device, used to measure BMD at the 1/3rd radius position. Fifty-two female first responders and healthcare providers were assessed using DXA (forearm, femur, lumbar, and total body) and the UltraScan650™. Fat and lean mass were also assessed using the DXA. Pearson correlations, Bland-Altman plots, t-tests, and linear regressions were used to assess validity. Intra-class correlation (ICC) coefficients were used to assess reliability. Inter-rater reliability and repeatability were good (ICC = 0.896 [0.818; 0.942], p < 0.001) and excellent (ICC = 0.917 [0.785; 0.989], p < 0.001), respectively. BMD as measured by the UltraScan650™ was weakly correlated to the DXA (r = 0.382 [0.121; 0.593], p = 0.0052). Bland-Altman plots revealed that the UltraScan650™ underestimated BMD (-0.0569 g/cm 2 ), this was confirmed with a significant paired t-test (p < 0.001). A linear regression was performed (0.4744 × UltraScan650™ + 0.4170) to provide more information as to the issue of agreement. Bland-Altman plots revealed a negligible bias, supported by a paired t-test (p = 0.9978). Pearson's correlation revealed a significant relationship (r = -0.771 [-0.862; -0.631], p < 0.0001) between adjusted UltraScan650™-DXA and the average of the two scans (i.e., adjusted UltraScan650™ and DXA), suggesting a proportional constant error and proportional constant variability in measurements of BMD from the UltraScan650™. The UltraScan650™ is not a valid alternative to DXA for diagnostic purposes; however, the UltraScan650™ could be used as a screening tool in the clinical and research setting given the linear transformation is employed., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Objectives: A history of childbirth is associated with musculoskeletal injury (MSKi) in female members of the Canadian Armed Forces (CAF). While previous injury and pregnancy impact knee kinematics, it is unclear if a history of childbirth is associated with medial knee displacement (MKD) in an overhead squat movement screen. The aim of this study is to examine the relationship between MKD and (1) MSKi and (2) parity status in female CAF members., Methods: 24 nulliparous and 21 parous female participants employed by the CAF completed a comprehensive physical fitness assessment of muscular flexibility, power, strength, endurance, aerobic capacity and a bodyweight overhead squat movement screen (recorded using two-dimensional video, and hip-knee-ankle angle measured using Kinovea software). Interactions between MKD, parity status and MSKi history were assessed by one-way analysis of variance and two-way analysis of covariance (ANCOVA) (adjusted for age)., Results: An interaction between parity status and acute injury of the lower extremity was observed (F=4.379, p=0.043, η 2 = 0.099) in MKD of the right knee. The two-way ANCOVA examining acute injury of the lumbopelvic hip complex (lower back, pelvis, hip) yielded an interaction between acute injury to the lumbopelvic hip complex and parity status (F=4.601, p=0.038, η 2 =0.103) in MKD asymmetry., Discussion: Parous participants with acute injury to the lower extremity had larger MKD than parous without this injury type. Parous participants without acute injury to the lumbopelvic hip complex had greater MKD asymmetry than nulliparous without this injury type. Our findings suggest that researchers and clinicians should consider parity status in conjunction with MSKi history when assessing knee kinematics in female military members., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Musculoskeletal injuries (MSKi) are the most common injury type experienced by first-responders and health care providers (HCPs), making them a significant threat to physical and mental well-being. Female reproductive health and injury history has been related to physical fitness in female members of the Canadian Armed Forces. This relationship has not been explored in Canadian protective services personnel (first-responders) or HCPs., Methods: Fifty-seven females employed as firefighters, paramedics, law enforcements, or HCPs completed a physical fitness protocol to assess the following: (1) muscular power (standing long jump and medicine ball throw), (2) muscular strength (4 repetition maximum (4RM) back squats and bench press), (3) muscular endurance (Biering-Sorenson test, single-leg wall sit, and push-ups), (4) flexibility (sit-and-reach), and (5) aerobic capacity (graded treadmill VO 2max test). Spearman rho correlation analyses were applied to descriptive analysis, independent-samples t -test, one-way ANCOVA (adjusted by age), and chi-square test. Spearman rho correlation analyses were used to compare physical fitness results for female reproductive health history ( e.g., parity status), previous MSKi, and physical activity behaviors ( e.g., sports participation). A p value of <0.05 is considered significant., Results: History of childbirth, body composition, and exercise behaviors were related to physical fitness ( i.e., standing long jump, Biering-Sorenson test, bench press, and back squat) in law enforcement, firefighting, paramedicine, and health care personnel., Conclusions: Physical training programs aimed at supporting parous first-responders or HCPs should emphasize lower body power, lower body strength, and upper body strength., (© C. M. Edwards et al., 2024; Published by Mary Ann Liebert, Inc.)

Circulating tumour cells (CTCs) are cancer cells shed from a primary tumour which intravasate into the blood stream and have the potential to extravasate into distant tissues, seeding metastatic lesions. As such, they can offer important insight into cancer progression with their presence generally associated with a poor prognosis. The detection and enumeration of CTCs is, therefore, critical to guiding clinical decisions during treatment and providing information on disease state. CTC isolation has been investigated using a plethora of methodologies, of which immunomagnetic capture and microfluidic size-based filtration are the most impactful to date. However, the isolation and detection of CTCs from whole blood comes with many technical barriers, such as those presented by the phenotypic heterogeneity of cell surface markers, with morphological similarity to healthy blood cells, and their low relative abundance (∼1 CTC/1 billion blood cells). At present, the majority of reported methods dissociate CTC isolation from detection, a workflow which undoubtedly contributes to loss from an already sparse population. This review focuses on developments wherein isolation and detection have been integrated into a single-step, microfluidic configuration, reducing CTC loss, increasing throughput, and enabling an on-chip CTC analysis with minimal operator intervention. Particular attention is given to immune-affinity, microfluidic CTC isolation, coupled to optical, physical, and electrochemical CTC detection (quantitative or otherwise)., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma., (© 2024. The Author(s).)

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling., (© 2024. The Author(s).)

Abstract: Edwards, CM, da Silva, DF, Puranda, JL, Souza, SCS, Semeniuk, K, and Adamo, KB. Associations between rank, sex, and parity with musculoskeletal injuries sustained during annual military physical fitness test. J Strength Cond Res 38(2): 367-373, 2024-Musculoskeletal injuries pose a significant threat to the well-being of military personnel. Attempts to use physical employment standard test results as predictors of injury are underway, but little is known about injuries sustained during the tests. This study sought to identify body regions most likely to be reported as injured during the annual Canadian Armed Forces (CAF) physical fitness evaluation. In addition, sex, rank, and parity status are explored as possible associated factors for injury. A total of 1,796 actively serving CAF members were categorized by sex (1,030 male participants; 766 female participants), rank (1,142 Non-Commissioned Members [NCM]; 638 Officers), and parity (314 parous female participants; 435 nulliparous female participants). Sex, rank, and parity were associated with body regions reportedly injured during an annual CAF fitness assessment (significance p ≤ 0.05). When compared with male participants, female participants were more likely to be injured {aOR: 1.797 (95% [confidence interval] CI: 1.45-2.23)} and more prone to injury of the wrist (adjusted odds ratio [aOR]: 1.933 [95% CI: 1.20-3.12]), hip (aOR: 3.445 [95% CI: 2.07-5.728]), or lower back (aOR: 1.55 [95% CI: 1.18-2.04]). Non-Commissioned Members were more likely to injure the neck (aOR: 2.14 [95% CI: 1.18-3.88]) or shoulder (aOR: 2.03 [95% CI: 1.31-3.15]), when compared with Officers. Parous female participants reported pelvis/abdomen injury at a higher rate than the nulliparous group (5 vs. 1.7%, p = 0.019). Injuries sustained during an annual CAF fitness assessment differ based on sex, rank, and parity. Canadian Armed Forces female participants, NCM, and parous female participants may require specific physical fitness support in preparation for the annual physical fitness test., (Copyright © 2023 National Strength and Conditioning Association.)

Regions of hypoxia occur in most tumors and are a predictor of poor patient prognosis. Hypoxia-activated prodrugs (HAPs) provide an ideal strategy to target the aggressive, hypoxic, fraction of a tumor, while protecting the normal tissue from toxicity. A key challenge associated with the development of novel HAPs, however, is the ability to visualize the delivery of the prodrug to hypoxic regions and determine where it has been activated. Here, we report a modified version of the commonly used nitroimidazole bioreductive group that incorporates the fluoroethyl epitope of the antibody-based hypoxia imaging agent, EF5. Attachment of this group to the red fluorescent dye, dicyanomethylene (DCM), enabled us to correlate the release of the DCM dye with imaging of the reduced bioreductive group using the EF5 antibody. This study confirmed that the antibody was imaging reduction and fragmentation of the pro-fluorophore. We next employed the modified bioreductive group to synthesize a new prodrug of the KDAC inhibitor Panobinostat, EF5-Pano. Release of EF5-Pano in hypoxic multiple myeloma cells was imaged using the EF5 antibody, and the presence of an imaging signal correlated with apoptosis and a reduction in cell viability. Therefore, EF5-Pano is an imageable HAP with a proven cytotoxic effect in multiple myeloma, which could be utilized in future in vivo experiments., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The effect of parity status on the prevalence and impact of musculoskeletal injury (MSKi) among female Canadian Armed Forces (CAF) members is unknown. This study aims to identify whether a history of childbirth and pregnancy-related complications are associated with MSKi occurrence among female members of the CAF. From September 2020 to February 2021, data were collected via an online questionnaire that assessed MSKi, reproductive health, and barriers to recruitment and retention in the CAF. Actively serving, female members were included in this analysis stratified by parous ( n  = 313) or nulliparous ( n  = 435) status. Descriptive analysis and binary logistic regressions were used to identify prevalence and adjusted odds ratios (aOR) of repetitive strain injuries (RSI), acute injuries, and body regions affected. Covariates included in aOR: age, body mass index, and rank. A p value of <0.05 was considered significant and 95% confidence intervals (CI) were reported. Female members with a history of childbirth were more likely to report an RSI (80.9% vs. 69.9%, OR = 1.57, CI: 1.03 to 2.40), and when stratified by body region, were more likely to have an RSI of the wrist (30.0% vs. 20.5%, aOR = 1.62, CI: 1.09 to 2.40), and foot (39.3% vs. 24.1%, aOR = 1.79, CI: 1.24 to 2.59). When compared to the nulliparous group, parity did not influence prevalence of acute injuries. MSKi and mental health perceptions were different for females who experienced postpartum depression, miscarriage, or preterm birth. Childbirth and pregnancy-related complications impact prevalence of some RSI among female CAF members. Thus, specific health and fitness support may be needed for parous female CAF members.

Sternoclavicular joint instability is a rare complaint in the orthopedic clinic, but patients can experience chronic pain and functional impacts. Causes of instability may be posttraumatic, infectious, autoimmune, degenerative, or secondary to generalized laxity. Conservative treatment is the initial approach to management and involves activity modification, physical therapy, oral nonsteroidal anti-inflammatory drugs, and corticosteroid injections. Surgery is indicated when conservative treatment does not manage symptoms. Figure-of-eight reconstruction techniques provide greatest biomechanical strength but are associated with risk of neurovascular injury. Other reconstruction methods have been shown to mitigate these risks with favorable short-term outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recent comprehensive systematic reviews indicate that females are at greater risk of musculoskeletal injuries (MSKi) than males in military populations. Considering the Canadian Armed Forces (CAF) goal of increasing female representation in the next few years, exploring these trends is essential. We aimed to determine the association between biological sex and MSKi in the CAF. An online survey was conducted with active-duty and former CAF members aged 18-65 years. Sex disparities in MSKi (acute or repetitive strain [RSI]) were analyzed using bivariate associations and binary logistic regressions with significance level at p  < 0.05. Analyses were stratified by military environment (i.e., Army, Navy, and Air Force). From the 1947 respondents whose biological sex was reported, 855 were females and 1092 were males. Rates of RSI sustained by females and males while serving were 76.2% and 70.5% ( p  = 0.011), respectively, whereas 61.4% of females reported acute injuries compared to 63.7% of males ( p  = 0.346). Females were more likely to report overall RSI (adjusted odds ratio [aOR]: 1.397; 95% confidence intervals [CI]: 1.068-1.829), RSI having a greater impact on daily activities (aOR [95%CI]: 2.979 [2.093-4.239]) and greater impact on career progress/length (aOR [95%CI]: 1.448 [1.066-1.968]). Acute injuries, also more prevalent in females, were reported to have a greater impact on daily activities (aOR [95%CI]: 1.688 [1.198-2.379]). This study highlights sex disparities in MSKi prevalence and outcomes. Females within the CAF sample presented greater likelihood of reporting RSI, perceived impact of RSI on daily activities and career progress/length, and perceived impact of acute injuries on daily activities.

This chapter provides an overview of the prevalence of clavicle fractures in athletes. The evaluation and management of clavicle fractures in athletes is summarized, including surgical considerations, rehabilitation protocols, and return to sport guidelines. In this population, high rates of union are observed, but careful timing of return to sport is paramount to optimize performance and prevent reinjury., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Urinary incontinence (UI) and pelvic organ prolapse (POP) are prevalent pelvic floor disorders (PFDs) among the female population. In the military environment, being a non-commissioned member (NCM), and physically demanding occupations are factors associated with higher PFD risk. This study seeks to characterize the profile of female Canadian Armed Forces (CAF) members reporting symptoms of UI and/or POP., Methods: Present CAF members (18-65 years) responded to an online survey. Only current members were included in the analysis. Symptoms of UI and POP were collected. Multivariate logistic regressions analyzed the relationships between PFD symptoms and associated characteristics., Results: 765 active members responded to female-specific questions. The prevalence of self-reported POP and UI symptoms were 14.5% and 57.0%, respectively, with 10.6% of respondents reporting both. Advanced age (adjusted odds ratio [aOR]: 1.062, CI 1.038-1.087), a body mass index (BMI) categorized as obese (aOR: 1.909, [1.183-3.081]), parity ≥1 (e.g., aOR for 1: 2.420, [1.352-4.334]) and NCMs (aOR: 1.662, [1.144-2.414]) were factors associated with urine leakage. Parity of ≥2 (aOR: 2.351, [1.370-4.037]) compared to nulliparous and having a perception of a physically demanding job (aOR: 1.933, [1.186-3.148]) were associated with experiencing POP symptoms. Parity of ≥2 increased the odds of reporting both PFD symptoms (aOR: 5.709, [2.650-12.297])., Conclusion: Parity was associated with greater odds of experiencing symptoms of UI and POP. Higher age, higher BMI, and being an NCM were associated with more symptoms of UI, and the perception of having a physically demanding role increased the likelihood of reporting POP symptoms., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background Preoperative anxiety is common in children undergoing surgery. When anxiety is identified or suspected, there are several strategies typically used to manage it. Perhaps the most common is anxiolytic premedication or parental presence at induction. Medications such as midazolam have been associated with adverse effects, such as a slower wakeup, and require timing of administration, while parental presence can be disturbing to the parent and divert the attention of the operating room team. A more recent option is distraction via electronic tablets. The purpose of this study was to retrospectively investigate and quantify any change in the use of midazolam, the most common anxiolytic approach at our institution, and any change in the length of time in the post-anesthesia care unit (PACU) following the introduction of tablet computers to a pediatric ambulatory surgical center. Methods We conducted an IRB-approved retrospective chart review of 13,790 pediatric patients ages one to 18 undergoing outpatient elective surgeries at the University of Florida (UF) Children's Surgical Center over a five-year period. A univariate analysis was conducted using the Fisher's Exact test and interrupted time series analysis to determine differences between midazolam administration and PACU times, with interruption occurring at tablet implementation. A multivariable analysis and sensitivity analyses were performed to confirm the findings of the univariate analysis. Results On univariate analysis, tablet availability was associated with both a decreased preoperative oral midazolam administration (odds ratio (OR) 0.158, 95% confidence interval (CI): 0.140 to 0.179, P-value <0.001) and a decreased PACU length of stay (-17.4 min, 95% CI: -19.6 to -15.3 min, P-value <0.001). The association with decreased preoperative midazolam administration held after multivariable analysis (adjusted OR 0.207, 95% CI: 0.154 to 0.278, P-value <0.001), but PACU length of stay was not statistically significant (-9.1 min, 95% CI: -20.6 to 2.4, P-value = 0.12). These results were confirmed on sensitivity analysis, with tablet availability continuing to be associated with decreased preoperative oral midazolam administration but not with reduced PACU length of stay. Conclusion Our results demonstrate that computer tablets were associated with a significant decrease in the frequency of midazolam administration and consequently may reduce preoperative pediatric anxiety. We did not find an associated change in PACU length of stay following the introduction of tablets. Tablets present a unique distraction alternative to chemical anxiolysis for institutions seeking to reduce medication use in pediatric patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Farlie et al.)

Although treatment of multiple myeloma (MM) with daratumumab significantly extends the patient's lifespan, resistance to therapy is inevitable. ISB 1342 was designed to target MM cells from patients with relapsed/refractory MM (r/r MM) displaying lower sensitivity to daratumumab. ISB 1342 is a bispecific antibody with a high-affinity Fab binding to CD38 on tumor cells on a different epitope than daratumumab and a detuned scFv domain affinity binding to CD3ε on T cells, to mitigate the risk of life-threatening cytokine release syndrome, using the Bispecific Engagement by Antibodies based on the TCR (BEAT) platform. In vitro, ISB 1342 efficiently killed cell lines with different levels of CD38, including those with a lower sensitivity to daratumumab. In a killing assay where multiple modes of action were enabled, ISB 1342 showed higher cytotoxicity toward MM cells compared with daratumumab. This activity was retained when used in sequential or concomitant combinations with daratumumab. The efficacy of ISB 1342 was maintained in daratumumab-treated bone marrow patient samples showing lower sensitivity to daratumumab. ISB 1342 induced complete tumor control in 2 therapeutic mouse models, unlike daratumumab. Finally, in cynomolgus monkeys, ISB 1342 displayed an acceptable toxicology profile. These data suggest that ISB 1342 may be an option in patients with r/r MM refractory to prior anti-CD38 bivalent monoclonal antibody therapies. It is currently being developed in a phase 1 clinical study., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: The environmental impact of inhaled anesthetics is a subject of increasing research. However, little attention has been paid to optimizing high-concentration volatile anesthetics during the inhalational (mask) inductions that begin most pediatric anesthetics., Methods: The performance of the GE Datex Ohmeda TEC 7 sevoflurane vaporizer was analyzed at different fresh gas flow (FGF) rates and two clinically relevant ambient temperatures. We found that an FGF rate of 5 liters per minute (LPM) is likely optimal for inhalational inductions, rapidly achieving dialed sevoflurane concentrations at the elbow of an unprimed pediatric breathing circuit while minimizing waste associated with higher FGF rates. We began educating our department regarding these findings, first with QR code labels on anesthetic workstations, then with targeted e-mails to pediatric anesthesia teams. We analyzed peak induction FGF in 100 consecutive mask inductions at our ambulatory surgery center at three different periods - baseline, post-labels, and post-emails - to assess the efficacy of these educational interventions. We also analyzed the time from induction to the start of myringotomy tube placement in a subset of these cases to determine if reducing mask induction FGF was associated with any change in the speed of induction., Results: Our institution's median peak FGF during inhalational inductions decreased from 9.2 LPM at baseline to 8.0 LPM after labels were placed on anesthetic workstations to 4.9 LPM after targeted e-mails. There was no associated decrease in the speed of induction., Conclusion: Total fresh gas flow can be limited to 5 LPM during pediatric inhalational inductions, decreasing anesthetic waste and environmental impact without slowing the speed of induction. Educational labels on anesthetic workstations and direct e-mails to clinicians were effectively used in our department to enact change in this practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Edwards et al.)

Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)