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The absolute light yield of a scintillator, defined as the number of scintillation photons produced per unit energy deposited, is a useful quantity for scintillator development, research, and applications. Yet, literature data on the absolute light yield of organic scintillators are limited. The goal of this work is to assess the suitability of the EJ-204 plastic scintillator from Eljen Technology to serve as a reference standard for measurements of the absolute light yield of organic scintillators. Four EJ-204 samples were examined: two manufactured approximately four months prior and stored in high-purity nitrogen, and two aged approximately eleven years and stored in ambient air. The scintillator response was measured using a large-area avalanche photodiode calibrated using low energy γ-ray and X-ray sources. The product of the quantum efficiency of the photodetector and light collection efficiency of the housing was characterized using an experimentally-benchmarked optical photon simulation. The average absolute light yield of the fresh samples, 9100 ± 400 photons per MeV, is lower than the manufacturer-reported value of 10400 photons per MeV. Moreover, the aged samples demonstrated significantly lower light yields, deviating from the manufacturer specification by as much as 26%. These results are consistent with recent work showcasing environmental aging in plastic scintillators and suggest that experimenters should use caution when deploying plastic scintillators in photon counting applications.

Aims:: The aim of this study is to report the relationship between bladder compliance and nocturia in men presenting with a variety of lower urinary tract symptoms, and to clarify the level at which bladder compliance becomes an important contributor to nocturia. Methods:: We report the results of a retrospective analysis of 104 men who presented to a single center with lower urinary tract symptoms and subsequently underwent urodynamic studies and completed a 24-hour bladder diary. Regression analyses to predict the determinants of nocturia and bladder compliance were completed, and the difference in actual number of nightly voids (ANV) was determined for those above and below 3 different cut-offs for bladder compliance: 20, 40, and 60 mL/cm H2O. Results:: Bladder compliance is inversely related to nocturia, likely due to the relationships between age, maximum voided volume, and bladder compliance. Significant differences in ANV exist between the men above and below the bladder compliance cut-offs of 40 and 60 mL/cm H2O, with the greatest difference seen at the cut-off of 60. Conclusions:: Bladder compliance < 60 mL/cm H2O appears to be a minor contributing factor to nocturia severity that is overshadowed by other bladder diary variables.

Purpose: The purpose of this article is to compare the efficacy of two prominent medications utilized in smoking cessation: bupropion and varenicline. Data sources: Comprehensive review of the literature on bupropion and varenicline including randomized control trials, government reports, journal reviews, and pharmaceutical inserts. Conclusions: In all studies comparing varenicline to bupropion and/or placebo, varenicline yielded a greater cessation rate at both 3 and 12 months. Additionally, varenicline 1 mg indicated an increased potential for long-term cessation success when compared with varenicline 0.5 mg. When compared with only placebo, bupropion demonstrated a higher efficacy for cessation both at 3 and 12 months. Implications for practice: Only 6% of the 20 million smokers who attempt to quit will succeed in long term. Clinicians must assess their patient's willingness to quit and educate them about cessation options. Knowing the efficacy of various treatment options for patients will potentially increase their success at quitting smoking. Understanding the treatment options available, allows for clinicians to provide the best possible method for smoking cessation for their patient population. [ABSTRACT FROM AUTHOR]

Objective: To determine risk of delivering a preterm infant (<37 weeks) in overweight/obese women. Design: Descriptive. Sample: Population-based sample of 169,881 singleton Missouri birth certificate records for 1998-2000. Measures: Prepregnancy body mass index (BMI): underweight BMI<19.8; normal BMI=19.8-24.9; overweight BMI=25-29.9; and obese BMI>=30; and preterm birth (<37 completed weeks' gestation). Results: In each BMI category, the percent of women who delivered a preterm infant is: underweight 11.5%, normal 8.3%, overweight 8.2%, and obese 8.5%. For women with a BMI of overweight (odds ratio [OR] 0.9, 95% confidence interval [CI]=0.8-0.9) and obese (OR 0.8, 95% CI=0.8-0.9), the risk of delivering a preterm infant decreased when compared with women with a BMI<19.8. Black (OR=2.5, 95% CI 2.4-2.6) and Hispanic (OR=1.4, 95% CI 1.2-1.5) women had a higher risk of preterm birth than White women when obesity, diabetes, hypertension, and prenatal care were controlled. Women with diabetes (OR=1.4, 95% CI=1.2-1.5), hypertension (OR=3.2, 95% CI=3.1-3.4), and those who smoked (OR=1.6, 95% CI=1.6-1.7) were at increased risk for a preterm birth. Conclusions: Findings suggest that preconception and prenatal care focus on identification and management of risks associated with premature births and maternal risk factors such as diabetes, hypertension, and smoking. [ABSTRACT FROM AUTHOR]

The purpose of this article is to provide information for health care professionals to guide the assessment of feeding and growth in breastfed infants. Tools to assist in the assessment of breastfeeding are discussed, as well as infant weight, infant test-weighing, elimination, and growth patterns. We present in detail the research surrounding the development of infant growth charts and the potential for inaccurate assessment. [ABSTRACT FROM AUTHOR]

Our objective was to determine whether classification of birth weight as small, average, or large for gestational age using published fetal growth curves is predictive of a term infant's risk of hypoglycemia. This prospective, descriptive study measured and plotted birth weight measurements on six published fetal growth curves to classify infant birth weight as small, average, or large for gestational age. Glucose levels were measured 2 hours after birth to determine the prevalence of hypoglycemia. The sensitivity, specificity, and positive/negative predictive values were calculated for each fetal growth curve, and odds ratios were calculated. The patients were 157 clinically stable term Caucasian and African American infants of nondiabetic mothers from a community hospital in midwestern United States. Ten of the 20 (50%) infants with hypoglycemia were classified as average for gestational age on all six published fetal growth curves. Calculated odds ratios demonstrated that none of the six published fetal growth curves significantly predicted the risk of hypoglycemia based on classification of birth weight as small, average, or large for gestational age. The risk of hypoglycemia in term infants was not accurately predicted by classification of birth weight as small, average, or large for gestational age. Clinicians should use other methods to predict which term infants are at risk for hypoglycemia. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the effect of preoperative acetaminophen given as analgesia before circumcision on newborns' behavioral response. STUDY DESIGN AND METHODS: A convenience sample of 53 male newborn infants (GA 35 to 42 weeks) who were.24 hours of age and whose parents had consented to circumcision were enrolled in the study. All of the infants enrolled were the patients of providers who did not routinely use anesthesia for circumcision. They were assigned to two groups based on physician standing order for preoperative acetaminophen. The first group received oral acetaminophen during the preoperative period; the second group received no preoperative analgesia. No further analgesia or anesthesia was given, as was the customary policy. Behavioral observations using the Neonatal Inventory Pain Scale (NIPS) and physiologic monitoring occurred at 5 minutes preoperatively, during application of restraints, at 1-minute intervals intraoperatively and at 5, 15, 30, and 60 minutes postoperatively. RESULTS: There were no differences in the demographic variables between groups. The overall mean NIPS scores for the following characteristics were lower (indicating more relaxation) in newborns who received preoperative analgesia: arm movements (0.27 vs 0.52); leg movements (0.27 vs 0.59); facial expression (0.24 vs 0.27); state of arousal (0.15 vs 0.46); and breathing quality (0.20 vs 0.38). However, newborns who received pre-op analgesia had higher crying scores (0.42 vs 0.33), although both groups had mean crying scores in the lowest range. CLINICAL IMPLICATIONS: Despite its small sample size, this study suggests that preoperative analgesia before circumcision could be helpful in managing the pain of circumcision. Nurses have a responsibility to advocate for policy and practices changes that provide interventions for pain relief for all newborns. [ABSTRACT FROM AUTHOR]

Purpose: To describe and compare the intra- and inter-examiner reliability of three length measurement techniques and to determine if the three measurement techniques yield significantly different measurements. Method: Two experienced, mother-baby nurses each obtained length measurements using the supine, paper barrier, and AUTO-LENGTH measurement techniques twice each from 48 healthy term infants. The nurses were blind to their own and to each other's measurements. The order of the nurses and the order of the measurement techniques were randomized. Results: For intraexaminer reliability, RN-1 had smaller mean absolute differences for the Auto-length measurements. RN-2 had similar mean absolute differences for all three measurement techniques. The percentage of differences

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown., Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Patients who underwent revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline patient characteristics, surgical technique and pathology, and a series of validated patient-reported outcome instruments: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity rating score. Patients were followed up for 6 years and asked to complete the identical set of outcome instruments. Regression analysis was used to control for baseline patient characteristics and surgical variables to assess the surgical risk factors for clinical outcomes 6 years after surgery., Results: A total of 1234 patients were enrolled (716 men, 58%; median age, 26 years), and 6-year follow-up was obtained on 79% of patients (980/1234). Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in 6-year IKDC scores (odds ratio [OR], 2.2; 95% CI, 1.2-3.9; P = .008) and KOOS sports/recreation and quality of life subscale scores (OR range, 2.2-2.7; 95% CI, 1.2-4.8; P < .01). Use of an interference screw compared with a cross-pin resulted in a 2.6 times less likely chance of having a subsequent surgery within 6 years. Use of an interference screw for tibial fixation compared with any combination of tibial fixation techniques resulted in significantly improved scores for IKDC (OR, 1.96; 95% CI, 1.3-2.9; P = .001); KOOS pain, activities of daily living, and sports/recreation subscales (OR range, 1.5-1.6; 95% CI, 1.0-2.4; P < .05); and WOMAC pain and activities of daily living subscales (OR range, 1.5-1.8; 95% CI, 1.0-2.7; P < .05). Use of a transtibial surgical approach compared with an anteromedial portal approach resulted in significantly improved KOOS pain and quality of life subscale scores at 6 years (OR, 1.5; 95% CI, 1.02-2.2; P ≤ .04)., Conclusion: There are surgical variables at the time of ACL revision that can modify clinical outcomes at 6 years. Opting for a transtibial surgical approach and choosing an interference screw for femoral and tibial fixation improved patients' odds of having a significantly better 6-year clinical outcome in this cohort., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This project was funded by grant No. 5R01-AR060846 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. All author disclosures are listed in the Appendix (available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Asymptomatic Alzheimer's disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer's disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aβ, preserving brain health, and slowing AD pathology progression., (© 2024. The Author(s).)

Background: Postoperative venous thromboembolism (VTE) is a major source of morbidity and mortality. The use of thromboprophylaxis among surgeons is not well studied in autologous breast reconstruction. The purpose of this study was to determine the rate of VTE in patients with breast cancer undergoing autologous breast reconstruction and to compare the cost-effectiveness of postoperative chemoprophylactic agents., Methods: The TriNetX National Health Research Network database was used to identify patients with breast cancer who underwent autologous breast reconstruction surgery between 2002 and 2022. The incidence of VTE within the first 30 days of surgery was calculated. A break-even analysis was performed to determine the break-even rate of VTE at which a chemoprophylactic agent would be cost-effective., Results: A cohort of 8221 patients was identified in this study. The rate of VTE was significantly higher in those without anticoagulation (4.0%) compared with those who received anticoagulation (2.6%) ( P = 0.0008). The break-even analysis for heparin and enoxaparin cost-effectiveness yielded absolute risk reductions of 0.73% and 1.63% for high-risk patients requiring 30 days of therapy and 0.20% and 0.43% for moderate-risk patients requiring 7 days of therapy, respectively., Conclusions: The use of thromboprophylaxis significantly lowered the risk of VTE within 30 days after autologous breast reconstruction. Heparin appeared to be more cost-effective at preventing VTE compared with enoxaparin for both high- and moderate-risk patients. The presented model holds potential for other institution-specific variables that can be easily applied by plastic surgeons to determine the cost-effectiveness of any therapy., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Schwann cells are vital to development and maintenance of the peripheral nervous system and their dysfunction has been implicated in a range of neurological and neoplastic disorders, including NF2 -related schwannomatosis. We developed a novel human induced pluripotent stem cell (hiPSC) model to study Schwann cell differentiation in health and disease. We performed transcriptomic, immunofluorescence, and morphological analysis of hiPSC derived Schwann cell precursors (SPCs) and terminally differentiated Schwann cells (SCs) representing distinct stages of development. To validate our findings, we performed integrated, cross-species analyses across multiple external datasets at bulk and single cell resolution. Our hiPSC model of Schwann cell development shared overlapping gene expression signatures with human amniotic mesenchymal stem cell (hAMSCs) derived SCs and in vivo mouse models, but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we identified gene co-expression modules that are dynamically regulated during hiPSC to SC differentiation associated with ear and neural development, cell fate determination, the NF2 gene, and extracellular matrix (ECM) organization. By cross-referencing results between multiple datasets, we identified new genes potentially associated with NF2 expression. Our hiPSC model further provides a tractable platform for studying Schwann cell development in the context of human disease.

Pulmonary fibrosis is an interstitial scarring disease of the lung characterized by poor prognosis and limited treatment options. Tissue transglutaminase 2 (TG2) is believed to promote lung fibrosis by crosslinking extracellular matrix components and activating latent TGFβ. This study assessed physiologic pulmonary function and metabolic alterations in the mouse bleomycin model with TG2 genetic deletion. TG2-deficient mice demonstrated attenuated the fibrosis and preservation of lung function, with significant reduction in elastance and increases in compliance and inspiratory capacity compared to control mice treated with bleomycin. Bleomycin induced metabolic changes in the mouse lung that were consistent with increased aerobic glycolysis, including increased expression of lactate dehydrogenase A and increased production of lactate, as well as increased glutamine, glutamate, and aspartate. TG2-deficient mice treated with bleomycin exhibited similar metabolic changes but with reduced magnitude. Our results demonstrate that TG2 is required for a typical fibrosis response to injury. In the absence of TG2, the fibrotic response is biochemically similar to wild-type, but lesions are smaller and lung function is preserved. We also show for the first time that profibrotic pathways of tissue stiffening and metabolic reprogramming are interconnected, and that metabolic disruptions in fibrosis go beyond glycolysis., (© 2024 UCB Biopharma and The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: Hypothalamic signals potently stimulate energy expenditure by engaging peripheral mechanisms to restore energy homeostasis. Previous studies have identified several critical hypothalamic sites (e.g. preoptic area (POA) and ventromedial hypothalamic nucleus (VMN)) that could be part of an interconnected neurocircuit that controls tissue thermogenesis and essential for body weight control. However, the key neurocircuit that can stimulate energy expenditure has not yet been established., Methods: Here, we investigated the downstream mechanisms by which VMN neurons stimulate adipose tissue thermogenesis. We manipulated subsets of VMN neurons acutely as well as chronically and studied its effect on tissue thermogenesis and body weight control, using Sf1 Cre and Adcyap1 Cre mice and measured physiological parameters under both high-fat diet and standard chow diet conditions. To determine the node efferent to these VMN neurons, that is involved in modulating energy expenditure, we employed electrophysiology and optogenetics experiments combined with measurements using tissue-implantable temperature microchips., Results: Activation of the VMN neurons that express the steroidogenic factor 1 (Sf1; VMN Sf1 neurons) reduced body weight, adiposity and increased energy expenditure in diet-induced obese mice. This function is likely mediated, at least in part, by the release of the pituitary adenylate cyclase-activating polypeptide (PACAP; encoded by the Adcyap1 gene) by the VMN neurons, since we previously demonstrated that PACAP, at the VMN, plays a key role in energy expenditure control. Thus, we then shifted focus to the subpopulation of VMN Sf1 neurons that contain the neuropeptide PACAP (VMN PACAP neurons). Since the VMN neurons do not directly project to the peripheral tissues, we traced the location of the VMN PACAP neurons' efferents. We identified that VMN PACAP neurons project to and activate neurons in the caudal regions of the POA whereby these projections stimulate tissue thermogenesis in brown and beige adipose tissue. We demonstrated that selective activation of caudal POA projections from VMN PACAP neurons induces tissue thermogenesis, most potently in negative energy balance and activating these projections lead to some similar, but mostly unique, patterns of gene expression in brown and beige tissue. Finally, we demonstrated that the activation of the VMN PACAP neurons' efferents that lie at the caudal POA are necessary for inducing tissue thermogenesis in brown and beige adipose tissue., Conclusions: These data indicate that VMN PACAP connections with the caudal POA neurons impact adipose tissue function and are important for induction of tissue thermogenesis. Our data suggests that the VMN PACAP → caudal POA neurocircuit and its components are critical for controlling energy balance by activating energy expenditure and body weight control., Competing Interests: Declaration of competing interest Jonathan N. Flak and Travis S. Johnson have received research support from Eli Lilly and Company, United States for separate projects in their respective laboratories., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and is already studied using RNA-seq. In this study, we generate a large (325,025 cells and 49 patients) single cell multi-omic dataset and jointly quantify ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identify an association between one plasma cell subtype with myeloma progression that we call relapsed/refractory plasma cells (RRPCs). These cells are associated with chromosome 1q alterations, TP53 mutations, and higher expression of PHF19. We also identify downstream regulation of cell cycle inhibitors in these cells, possible regulation by the transcription factor (TF) PBX1 on chromosome 1q, and determine that PHF19 may be acting primarily through this subset of cells., (© 2024. The Author(s).)

Fibrotic remodeling is the primary driver of functional loss in chronic kidney disease, with no specific anti-fibrotic agent available for clinical use. Transglutaminase 2 (TG2), a wound response enzyme that irreversibly crosslinks extracellular matrix proteins causing dysregulation of extracellular matrix turnover, is a well-characterized anti-fibrotic target in the kidney. We describe the humanization and characterization of two anti-TG2 monoclonal antibodies (zampilimab [hDC1/UCB7858] and BB7) that inhibit crosslinking by TG2 in human in vitro and rabbit/cynomolgus monkey in vivo models of chronic kidney disease. Determination of zampilimab half-maximal inhibitory concentration (IC50) against recombinant human TG2 was undertaken using the KxD assay and determination of dissociation constant (Kd) by surface plasmon resonance. Efficacy in vitro was established using a primary human renal epithelial cell model of tubulointerstitial fibrosis, to assess mature deposited extracellular matrix proteins. Proof of concept in vivo used a cynomolgus monkey unilateral ureteral obstruction model of chronic kidney disease. Zampilimab inhibited TG2 crosslinking transamidation activity with an IC50 of 0.25 nM and Kd of <50 pM. In cell culture, zampilimab inhibited extracellular TG2 activity (IC50 119 nM) and dramatically reduced transforming growth factor-β1-driven accumulation of multiple extracellular matrix proteins including collagens I, III, IV, V, and fibronectin. Intravenous administration of BB7 in rabbits resulted in a 68% reduction in fibrotic index at Day 25 post-unilateral ureteral obstruction. Weekly intravenous administration of zampilimab in cynomolgus monkeys with unilateral ureteral obstruction reduced fibrosis at 4 weeks by >50%, with no safety signals. Our data support the clinical investigation of zampilimab for the treatment of kidney fibrosis., Competing Interests: T. S. Johnson, P. F. Watson, and D. Matthews are inventors on patent WO 2013/175229 A1 (Anti-transglutaminase 2 antibodies) relating to the discovery and humanization of zampilimab. C. Kettleborough and D. Matthews are/were employees of LifeArc who hold rights to patent WO 2013/175229 and may therefore benefit from its development. Z. Song is the CEO of Prisys Biotechnologies who developed and ran the cynomolgus UUO model. J. Ni was an employee of Prisys Biotechnologies at the time the study was conducted. L. Huang, J. Atkinson, K. Cain, J. Kennedy, B. Twomey, H. Bon, and T. S. Johnson are/were employees of UCB Pharma who in-licensed zampilimab from LifeArc and may hold/have access to stock options., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Breast milk feeding is vital to the health outcomes of the breastfeeding dyad. Nurses have a significant role to promote, educate, and support breastfeeding practices for breastfeeding dyads in diverse settings. Nurses should also promote breastfeeding awareness to normalize breastfeeding as the optimal food for infants. This pilot study investigated the effects of a basic breastfeeding educational module on the breastfeeding attitudes of prelicensure nursing students. There was a statistically significant change in attitudes from pretest and posttest. Developing a comprehensive breastfeeding module is a significant step to standardize education and promote breastfeeding best practices., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2023 National League for Nursing.)

Background: Following the integration of the electronic health record (EHR) into the healthcare system, concern has grown regarding EHR use on physician well-being. For surgical residents, time spent on the EHR increases the burden of a demanding, hourly restricted schedule and detracts from time spent honing surgical skills. To better characterize these burdens, we sought to describe EHR utilization patterns for plastic surgery residents., Methods: Integrated plastic surgery resident EHR utilization from March 2019 to March 2020 was extracted via Cerner Analytics at a tertiary academic medical center. Time spent in the EHR on-duty (0600-1759) and off-duty (1800-0559) in the form of chart review, orders, documentation, and patient discovery was analyzed. Statistical analysis was performed in the form of independent t tests and Analysis of Variance (ANOVA)., Results: Twelve plastic surgery residents spent a daily average of 94 ± 84 minutes on the EHR, one-third of which was spent off-duty. Juniors (postgraduate years 1-3) spent 123 ± 99 minutes versus seniors (postgraduate years 4-6) who spent 61 ± 49 minutes (P < 0.01). Seniors spent 19% of time on the EHR off-duty, compared with 37% for juniors (P < 0.01). Chart review comprised the majority (42%) of EHR usage, followed by patient discovery (22%), orders (14%), documentation (12%), other (6%), and messaging (1%). Seniors spent more time on patient discovery (25% vs 21%, P < 0.001), while juniors spent more time performing chart review (48% vs 36%, P = 0.19)., Conclusion: Integrated plastic surgery residents average 1.5 hours on the EHR daily. Junior residents spend 1 hour more per day on the EHR, including more time off-duty and more time performing chart review. These added hours may play a role in duty hour violations and detract from obtaining operative skill sets., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: After undergoing breast reconstructive surgery, patients are typically prescribed opioids. Smoking tobacco increases rate of opioid metabolism and is associated with development of opioid use disorder (OUD). The aim of this study was to determine whether patients who smoke have an increased risk of OUD after breast reconstructive surgery. Given that OUD is a known risk factor for injection drug use and intravenous drug use increases risk of acquiring blood-borne diseases including human immunodeficiency virus (HIV) and hepatitis, the secondary aim was to determine if these patients are also at increased risk of acquiring these communicable diseases associated with OUD., Methods: A retrospective analysis was conducted using TriNetX, a multi-institutional deidentified database. Individuals included underwent a breast reconstructive surgery and received postoperative opioid treatment. The exposed group included patients who smoke. The control group did not smoke. Risk of developing OUD, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV from 12 to 36 months after surgery was compared between groups. Patients with preexisting OUD or associated diseases were excluded. Cohorts were matched to control for confounding factors including age, sex, race, mental health history, and concomitant substance use., Results: There were 8648 patients included in the analysis. After matching, 4324 patients comprised the exposure group, and 4324 patients remained in the control group. Preoperative smoking was significantly associated with increased risk of OUD at 12, 24, and 36 months after breast reconstruction (36 months: odds ratio [OR], 2.722; confidence interval [CI], 2.268-6.375). Smoking was also associated with increased risk of HIV and HCV at all time points after surgery (36 months HIV: OR, 2.614; CI, 1.977-3.458; 36 months HCV: OR, 3.718; CI, 2.268-6.375) and increased risk of HBV beginning at 24 months after surgery (36 months HBV: OR, 2.722; CI, 1.502-4.935)., Conclusions: Individuals who smoke have an increased risk of developing OUD, HIV, HCV, and HBV after breast reconstructive surgery. This risk persists for at least 3 years after surgery. Additional research and clinical interventions focusing on early identification of OUD, prevention efforts, and harm reduction strategies for patients who smoke or have nicotine dependence undergoing breast reconstruction are warranted., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy., Methods: We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing., Results: Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39-77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2-62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7-29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4-61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2-62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype., Conclusions: Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

With antimicrobial resistance (AMR) remaining a persistent and growing threat to human health worldwide, membrane-active peptides are gaining traction as an alternative strategy to overcome the issue. Membrane-embedded multi-drug resistant (MDR) efflux pumps are a prime target for membrane-active peptides, as they are a well-established contributor to clinically relevant AMR infections. Here, we describe a series of transmembrane peptides (TMs) to target the oligomerization motif of the AcrB component of the AcrAB-TolC MDR efflux pump from Escherichia coli. These peptides contain an N-terminal acetyl-A-(Sar) 3 (sarcosine; N-methylglycine) tag and a C-terminal lysine tag-a design strategy our lab has utilized to improve the solubility and specificity of targeting for TMs previously. While these peptides have proven useful in preventing AcrB-mediated substrate efflux, the mechanisms by which these peptides associate with and penetrate the bacterial membrane remained unknown. In this study, we have shown peptide hydrophobic moment (μH)-the measure of concentrated hydrophobicity on one face of a lipopathic α-helix-drives bacterial membrane permeabilization and depolarization, likely through lateral-phase separation of negatively-charged POPG lipids and the disruption of lipid packing. Our results show peptide μH is an important consideration when designing membrane-active peptides and may be the determining factor in whether a TM will function in a permeabilizing or non-permeabilizing manner when embedded in the bacterial membrane., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze PeriData.Net, a clinical registry with linked maternal-infant hospital data of Milwaukee County residents, to demonstrate a predictive analytic approach to perinatal infant risk assessment., Materials and Methods: Using unsupervised learning, we identified infant birth clusters with similar multivariate health indicator patterns, measured using perinatal variables from 2008 to 2019 from n  = 43 969 clinical registry records in Milwaukee County, WI, followed by supervised learning risk-propagation modeling to identify key maternal factors. To understand the relationship between socioeconomic status (SES) and birth outcome cluster assignment, we recoded zip codes in Peridata.Net according to SES level., Results: Three self-organizing map clusters describe infant birth outcome patterns that are similar in the multivariate space. Birth outcome clusters showed higher hazard birth outcome patterns in cluster 3 than clusters 1 and 2. Cluster 3 was associated with lower Apgar scores at 1 and 5 min after birth, shorter infant length, and premature birth. Prediction profiles of birth clusters indicate the most sensitivity to pregnancy weight loss and prenatal visits. Majority of infants assigned to cluster 3 were in the 2 lowest SES levels., Discussion: Using an extensive perinatal clinical registry, we found that the strongest predictive performance, when considering cluster membership using supervised learning, was achieved by incorporating social and behavioral risk factors. There were inequalities in infant birth outcomes based on SES., Conclusion: Identifying infant risk hazard profiles can contribute to knowledge discovery and guide future research directions. Additionally, presenting the results to community members can build consensus for community-identified health and risk indicator prioritization for intervention development., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Objective: Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts., Methods: We assessed TG2 expression and activity using TG2 staining, Western blotting, and TG2 activity assays. We inhibited TG2 in fibroblasts cultured under standard 2-dimensional conditions and in a 3-dimensional full-thickness equivalent skin model using monoclonal inhibitory anti-TG2 antibodies., Results: TG2 expression was increased in the skin of patients with SSc compared with healthy controls, with levels particularly high in patients with SSc-associated interstitial lung disease. TG2 expression and TG2 activity were also increased in SSc dermal fibroblasts. Moreover, the levels of circulating TG2 in the plasma samples from SSc patients were increased versus samples from healthy controls. Anti-TG2 antibodies did not show consistent antifibrotic effects across different fibroblast cell lines under 2-dimensional culture conditions; however, anti-TG2 antibodies effectively reduced transforming growth factor β-induced dermal thickening, myofibroblast differentiation, and collagen accumulation in the 3-dimensional full-thickness model of human skin., Conclusion: We provide the first evidence, to our knowledge, that inhibition of TG2 might be a potential antifibrotic approach in SSc. Our findings have translational potential as anti-TG2 antibodies are currently evaluated in a phase II clinical trial in chronic allograft injury and would thus be available for clinical studies in SSc (ClinicalTrials.gov identifier: NCT04335578)., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

High-fat diet (HFD) is associated with Alzheimer's disease (AD) and type 2 diabetes risk, which share features such as insulin resistance and amylin deposition. We examined gene expression associated with astrocytes and microglia since dysfunction of these cell types is implicated in AD pathogenesis. We hypothesize gene expression changes in disease-associated astrocytes (DAA), disease-associated microglia and human Alzheimer's microglia exist in diabetic and obese individuals before AD development. By analyzing bulk RNA-sequencing (RNA-seq) data generated from brains of mice fed HFD and humans with AD, 11 overlapping AD-associated differentially expressed genes were identified, including Kcnj2, C4b and Ddr1, which are upregulated in response to both HFD and AD. Analysis of single cell RNA-seq (scRNA-seq) data indicated C4b is astrocyte specific. Spatial transcriptomics (ST) revealed C4b colocalizes with Gfad, a known astrocyte marker, and the colocalization of C4b expressing cells with Gad2 expressing cells, i.e., GABAergic neurons, in mouse brain. There also exists a positive correlation between C4b and Gad2 expression in ST indicating a potential interaction between DAA and GABAergic neurons. These findings provide novel links between the pathogenesis of obesity, diabetes and AD and identify C4b as a potential early marker for AD in obese or diabetic individuals., (© 2023. Springer Nature Limited.)

Introduction: With an increasing focus on multimodal pain control to reduce opioid requirements, regional and local anesthesia techniques have been investigated in bilateral reduction mammaplasty with variable results. The purpose of this study is to compare tumescent anesthesia with pectoral nerve block II (PECS II) in patients undergoing bilateral reduction mammaplasty with respect to postoperative pain and nausea, opioid consumption, length of stay, and cost., Methods: A retrospective review of patients undergoing bilateral reduction mammaplasty for macromastia between November 2020 and December 2021 was performed. Demographic information, operative and anesthesia times, antiemetic and morphine equivalent requirements, postoperative numeric pain rating scales, and time until hospital discharge were compared between groups. χ2 and Fisher exact tests examined subgroup differences in categorical variables. Two-sample t test and Wilcoxon rank-sum test evaluated differences in continuous parametric and nonparametric variables, respectively., Results: Fifty-three patients underwent bilateral reduction mammaplasty by 3 surgeons, 71.7% (n = 38) with tumescent anesthesia infiltrated by the operating surgeon before the start of the procedure and 28.3% (n = 15) with bilateral PECS II blocks performed by anesthesia before the start of the procedure. There was no difference in age, body mass index, weight resected, intraoperative medication, or immediate postoperative complications. Postoperative pain scores and opioid requirements were similar between the 2 groups. Twenty-one percent (n = 8) of tumescent patients compared with 66.7% (n = 10) of block patients required 1 or more doses of postoperative antiemetics ( P = 0.002). Patients who received blocks spent longer in the postoperative recovery area (5.3 vs 7.1 hours, P < 0.01). However, this did not translate to a significant increase in overnight stays. The block group had significantly higher hospitalization cost by an average of $4000, driven by pharmacy and procedural cost ( P < 0.01)., Conclusion: In this cohort of multimodal perioperative pain-controlled reduction mammaplasty patients, tumescent anesthesia was associated with decreased antiemetic requirements, less time in recovery before discharge, and lower cost compared with PECS II blocks. Therefore, tumescent anesthesia may be favored over PECS II blocks when considering multimodal pain control strategies in reduction mammaplasty patients., Competing Interests: Conflict of Interests: The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript. Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)