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E David Crawford, Jason M PhillipsUniversity of Colorado Health Sciences Center, Aurora, CO, USAAbstract: Two different 6-month GnRH agonist depot formulations approved for palliative treatment of advanced and metastatic prostate cancer in the United States – leuprolide acetate 45 mg and triptorelinpalmoate 22.5 mg – provide patients with efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH agonist depots. However, the 6-month formulations can increase patient convenience, comfort, and compliance by reducing the number of physician visits and injections required. At the conclusion of their pivotal trials, the 6-month formulations demonstrated efficacy rates in achieving chemical castration (serum testosterone #50 ng/dL) that ranged between 93% and 99%. As with existing GnRH agonist depot formulations, hot flashes represented the most common adverse event reported in trials of 6-month leuprolide acetate or triptorelin. As such, these products may prove useful not only for their labeled indication, but also as adjuncts to other treatments such as radical prostatectomy, radiotherapy, and chemotherapy. We recommend further research, including head-to-head trials between the 6-month GnRH depots, to refine our understanding of these products.Keywords: prostate cancer, leuprorelin, leuprolide, triptorelin, 6-month depot, testosterone

Breast cancer mortality is higher among African-American women than among White women. African-American women are 25% more likely to present with late stage breast cancer and 20% more likely to die from breast cancer than White women. Treatment delay of 3 months is a significant factor in breast cancer mortality The purpose of this integrative review is to explore factors that impact delays in screening The most common patient-controlled delays were lack of education and knowledge about the perceived seriousness of breast symptoms, the associated risk factors, limited knowledge regarding the potential benefits of early detection in improving breast cancer survival, and expressed fatalistic perspectives about breast cancer. Other variables related to delays included factors such as advancing age, low socioeconomic status, fear of diagnosis, consequences of cancer treatments, shame and embarrassment, misconceptions about the etiology of breast cancer, family priorites, denial, and spirituality including faith-influenced delays. [ABSTRACT FROM AUTHOR]

Plasma glial fibrillary acidic protein (GFAP) is an emerging biomarker of Alzheimer's disease (AD), with higher blood GFAP levels linked to faster cognitive decline, particularly among individuals with high brain amyloid burden. However, few studies have examined brain GFAP expression to clarify if peripheral associations reflect brain changes. This study aimed to correlate region-specific GFAP mRNA expression (n = 917) and protein abundance (n=386) with diverse neuropathological measures at autopsy in the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) and to characterize the interaction between brain GFAP and brain amyloid burden on downstream outcomes. We assessed GFAP gene expression in the dorsolateral prefrontal cortex, caudate nucleus, and posterior cingulate cortex with respect to core AD pathology (amyloid-β and tau), cerebrovascular (microinfarcts, macroinfarcts, and cerebral amyloid angiopathy [CAA]), proteinopathic (TDP-43, Lewy bodies), and cognitive outcomes. These associations were further examined at the protein level using tandem-mass tag proteomic measurements from the dorsolateral prefrontal cortex. We also assessed GFAP interactions with AD neuropathology on downstream outcomes. Cortical GFAP gene and protein expression were significantly upregulated in participants with a neuropathologically confirmed AD diagnosis at autopsy (all P FDR  < 3.5e-4), but not in individuals positive for tau pathology and negative for amyloid pathology (all P FDR  > 0.05). Higher cortical GFAP levels were associated with increased amyloid pathology, CAA pathology, and faster cognitive decline (all P FDR  < 3.3e-3). GFAP's associations with phosphorylated tau burden and cognition were influenced by amyloid burden, being most pronounced among amyloid-positive individuals, confirming previous in vivo biomarker observations. No associations were observed between GFAP gene expression and outcomes in the caudate nucleus. Our results support previous biomarker findings and suggest that higher brain GFAP levels are associated with higher brain amyloid burden and faster cognitive decline among amyloid-positive individuals., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval and consent to participate: This study adhered to the principles outlined in the Declaration of Helsinki. All protocols received approval from the Rush University Medical Center Institutional Review Board, and written informed consent, including the Anatomical Gift Act, was obtained from all participants. The secondary analyses were approved by the Vanderbilt University Medical Center Institutional Review Board under protocol number 170135. Consent for publication: All authors have given consent to the publication of this manuscript., (© 2024. The Author(s).)

Flexible behavior depends on abstract rules to generalize beyond specific instances, and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BG), enable thalamus to select rules. We measured activity across PFC and connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in ventroanterior thalamus (VA) - the main thalamic hub between BG and PFC. Mediodorsal thalamus (MD) also represented rule information before PFC, persisting to help maintain activation of relevant PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was first to represent information about behavioral outcomes. A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. This suggests that thalamus selects high-level cognitive information from PFC and monitors behavioral outcomes of these selections.

Alzheimer's disease (AD) is a polygenic disorder with a prolonged prodromal phase, complicating early diagnosis. Recent research indicates that increased astrocyte reactivity is associated with a higher risk of pathogenic tau accumulation, particularly in amyloid-positive individuals. However, few clinical tools are available to predict which individuals are likely to exhibit elevated astrocyte activation and, consequently, be susceptible to hyperphosphorylated tau-induced neurodegeneration. Polygenic risk scores (PRS) aggregate the effects of multiple genetic loci to provide a single, continuous metric representing an individual's genetic risk for a specific phenotype. We hypothesized that an astrocyte activation PRS could aid in the early detection of faster clinical decline. Therefore, we constructed an astrocyte activation PRS and assessed its predictive value for cognitive decline and AD biomarkers (i.e., cerebrospinal fluid [CSF] levels of Aβ1-42, total tau, and p-tau181) in a cohort of 791 elderly individuals. The astrocyte activation PRS showed significant main effects on cross-sectional memory (β = -0.07, p = 0.03) and longitudinal executive function (β = -0.01, p = 0.03). Additionally, the PRS interacted with amyloid positivity (p.intx = 0.02), whereby indicating that amyloid burden modifies the association between the PRS and annual rate of language decline. Furthermore, the PRS was negatively associated with CSF Aβ1-42 levels (β = -3.4, p = 0.07) and interacted with amyloid status, such that amyloid burden modifies the association between the PRS and CSF phosphorylated tau levels (p.intx = 0.08). These findings suggest that an astrocyte activation PRS could be a valuable tool for early disease risk prediction, potentially enabling intervention during the interval between pathogenic amyloid and tau accumulation.

Scalar field comparison is a fundamental task in scientific visualization. In topological data analysis, we compare topological descriptors of scalar fields-such as persistence diagrams and merge trees-because they provide succinct and robust abstract representations. Several similarity measures for topological descriptors seem to be both asymptotically and practically efficient with polynomial time algorithms, but they do not scale well when handling large-scale, time-varying scientific data and ensembles. In this paper, we propose a new framework to facilitate the comparative analysis of merge trees, inspired by tools from locality sensitive hashing (LSH). LSH hashes similar objects into the same hash buckets with high probability. We propose two new similarity measures for merge trees that can be computed via LSH, using new extensions to Recursive MinHash and subpath signature, respectively. Our similarity measures are extremely efficient to compute and closely resemble the results of existing measures such as merge tree edit distance or geometric interleaving distance. Our experiments demonstrate the utility of our LSH framework in applications such as shape matching, clustering, key event detection, and ensemble summarization.

Background: Virtual reality simulation (VRS) is an innovative modality in nursing professional development that has the potential to affect patient outcomes., Method: An experimental cluster randomized controlled trial was performed with RNs on two inpatient units at a large academic health system. The purpose of this study was to evaluate the effect of VRS compared with traditional education on Clostridium difficile rates. Return on investment of nursing professional development activities was also measured to support decision-making and resource allocation., Results: Rates of C. difficile infection were significantly lower for both groups for the 3-month postintervention period compared with the 10-month period preintervention. Financial analysis showed a return on investment for both modalities, with VRS having higher yields over time., Conclusion: Findings showed that VRS was an effective instructional method. [ J Contin Educ Nurs. 2024;55(7):351-358.] .

Objective: Severe maternal morbidity (SMM) has disproportionate frequencies among racial minorities and those of socioeconomic disadvantage, with people of Black race consistently having the highest proportion. Neighborhood level deprivation has been associated with maternal morbidity and mortality, including adverse pregnancy outcomes. We sought to explore the relationship between neighborhood socioeconomic disadvantage and SMM and describe how neighborhood context impacts the relationship between race and SMM., Study Design: We performed a retrospective cohort analysis of all delivery admissions in a single health care network from 2015 to 2019. Area deprivation index (ADI) was used to represent neighborhood socioeconomic disadvantage and is a composite index of neighborhood that spans income, education, household characteristics, and housing. The index ranges from 1 to 100 with higher values indicating higher disadvantage. Logistic regression assessed the relationship between ADI and SMM and estimated the effect that ADI has on the relationship between race and SMM., Results: Of the 63,208 birthing persons in our cohort, the unadjusted incidence of SMM was 2.2%. ADI was significantly associated with SMM, with higher values conferring higher risk for SMM ( p  < 0.001). The absolute risk of SMM increased roughly by 1.0% from the lowest to highest ADI value. Those of Black race had the highest unadjusted incidence of SMM compared with the referent group (3.4 vs. 2.0%) and highest median ADI (92; interquartile range [IQR]: 20). In the multivariable model, in which the primary exposure was race and ADI was adjusted for, Black race had a 1.7 times odds SMM when compared with White race (95% confidence interval [CI]: 1.5-1.9). This association was attenuated to 1.5 adjusted odds when controlling for ADI (95% CI: 1.3-1.7). Risk attenuation for SMM was not seen in other race categories., Conclusion: Neighborhood context contributes to SMM but does not explain the majority of racial disparities., Key Points: · Neighborhood context is associated with SMM, with higher disadvantage conferring higher risk.. · Compared with White race, all other races had higher rates of SMM, with Black race having the highest.. · Accounting for neighborhood modestly attenuates the magnitude of association of Black race with SMM.. · Neighborhood context contributes to health outcomes but does not explain the majority of disparities.., Competing Interests: H.N.S. reports grants from the NIH, CDC, and Gates Foundations, royalties or licenses from Uptodate, consulting fees from Organon, and is a founder of Naima Health LLC., (Thieme. All rights reserved.)

Despite the popularity of social skills groups, there remains a need for empirical investigation of treatment effects, especially when targeting pivotal aspects of social functioning such as initiations to peers. The goal of the present study was to conduct a randomized controlled trial of a 12-week social intervention (SUCCESS), which combined an inclusive social group with a parent education program. Twenty-five 4- to 6-year-olds with Autism Spectrum Disorder (ASD) were randomized to SUCCESS (N = 11) or to treatment as usual (N = 14). Combining a peer group model with a parent training program, the SUCCESS intervention used naturalistic behavioral techniques (e.g., environmental arrangement, natural reinforcement) to increase social initiations to peers. After 12 weeks, children participating in the SUCCESS program made more frequent initiations to peers than children in the treatment-as-usual group, including more prompted and unprompted initiations to request. Additional gains in clinician-rated social functioning were observed in children randomized to SUCCESS, while differential treatment effects were not detected in parent-rated measures. However, lower baseline social motivation was associated with greater parent-reported initiation improvement. This study provides preliminary support for the efficacy of a naturalistic, behavioral social skills intervention to improve peer initiations for children with ASD. The findings suggest that using a motivation-based social skills group was effective in increasing both prompted and spontaneous initiations to peers, and highlights the need for further research into the role of baseline social motivation in predicting social skills treatment response., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Virtual reality simulation (VRS) has emerged as an educational methodology in nursing professional development. A cluster randomized controlled trial was conducted with a sample of clinical registered nurses to compare effectiveness of VRS and traditional education on knowledge and behavior related to Clostridioides difficile prevention. No significant differences were found in the effectiveness of the two modalities, suggesting the usefulness of VRS as a teaching methodology., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current postpartum hemorrhage (PPH) risk stratification is based on traditional statistical models or expert opinion. Machine learning could optimize PPH prediction by allowing for more complex modeling., Objective: We sought to improve PPH prediction and compare machine learning and traditional statistical methods., Methods: We developed models using the Consortium for Safe Labor data set (2002-2008) from 12 US hospitals. The primary outcome was a transfusion of blood products or PPH (estimated blood loss of ≥1000 mL). The secondary outcome was a transfusion of any blood product. Fifty antepartum and intrapartum characteristics and hospital characteristics were included. Logistic regression, support vector machines, multilayer perceptron, random forest, and gradient boosting (GB) were used to generate prediction models. The area under the receiver operating characteristic curve (ROC-AUC) and area under the precision/recall curve (PR-AUC) were used to compare performance., Results: Among 228,438 births, 5760 (3.1%) women had a postpartum hemorrhage, 5170 (2.8%) had a transfusion, and 10,344 (5.6%) met the criteria for the transfusion-PPH composite. Models predicting the transfusion-PPH composite using antepartum and intrapartum features had the best positive predictive values, with the GB machine learning model performing best overall (ROC-AUC=0.833, 95% CI 0.828-0.838; PR-AUC=0.210, 95% CI 0.201-0.220). The most predictive features in the GB model predicting the transfusion-PPH composite were the mode of delivery, oxytocin incremental dose for labor (mU/minute), intrapartum tocolytic use, presence of anesthesia nurse, and hospital type., Conclusions: Machine learning offers higher discriminability than logistic regression in predicting PPH. The Consortium for Safe Labor data set may not be optimal for analyzing risk due to strong subgroup effects, which decreases accuracy and limits generalizability., (©Homa Khorrami Ahmadzia, Alexa C Dzienny, Mike Bopf, Jaclyn M Phillips, Jerome Jeffrey Federspiel, Richard Amdur, Madeline Murguia Rice, Laritza Rodriguez. Originally published in JMIR Bioinformatics and Biotechnology (https://bioinform.jmir.org), 05.02.2024.)

Objective: The aims of this study were to evaluate nursing caregiver well-being and identify interventions for improving well-being and practice environments., Background: Healthcare worker well-being and burnout command increasing attention in the wake of the pandemic. Experts recommend utilization of validated measurements to assess burnout, well-being, and contributing factors., Methods: Using a descriptive, cross-sectional, mixed-methods study design, an online survey, which included the Professional Quality of Life-5, Meaning and Joy in Work Questionnaire, and open-ended questions, was administered to nurses and unlicensed assistive caregivers in an academic health system., Results: Caregivers reported moderate compassion satisfaction, low burnout and compassion fatigue, and low-moderate levels of meaning and joy in work. Overall and subscale scores varied primarily based on age, experience, and role. Top causes of stress and recommendations for improvement were identified., Conclusion: The levels of meaning and joy in work among nursing caregivers continue to be of concern for organizational leaders. The engagement of nurses and other caregiver team members in a systematic mixed-methods approach, including using validated tools to evaluate caregiver well-being, can lead to meaningful, data-driven action planning to promote well-being and increase the meaning and joy of the work they perform., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The aim of our study is to describe maternal and neonatal morbidity and mortality in patients undergoing trial of labor after cesarean from the Consortium on Safe Labor., Methods: This was a secondary analysis of the Consortium on Safe Labor database, a retrospective cohort study over a 7 year study period. Maternal and neonatal outcomes were evaluated based on desired delivery mode: planned elective repeat cesarean delivery or trial of labor after cesarean., Results: Of 9858 patients in our analysis, our study population had 4400 patients (45%) who desired trial of labor after cesarean and 5458 patients (55%) who desired elective repeat cesarean delivery. Women who attempted trial of labor after cesarean compared to those who had an elective repeat cesarean delivery were more likely to have an obstetric hemorrhage (adjusted odds ratio 1.6; 95% CI 1.3 -2.0) and blood transfusion (adjusted odds ratio 2.3; 95% CI 1.6 -3.2)., Conclusion: Maternal morbidity in women undergoing trial of labor after cesarean was predominantly hemorrhage-related.

Objective: White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD., Method: Diffusion-weighted MRIs were obtained from same-sex twin pairs (6-15 years of age) in which at least 1 twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain, and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a novel Twin-Pair Difference Score analysis method that produces quantitative estimates of the genetic and environmental contributions to shared covariance between different brain and behavioral traits., Results: Good-quality data were available from 84 twin pairs, 50 ASD pairs (32 concordant for ASD [16 monozygotic; 16 dizygotic], 16 discordant for ASD [3 monozygotic; 13 dizygotic], and 2 pairs in which 1 twin had ASD and the other exhibited some subthreshold symptoms [1 monozygotic; 1 dizygotic]) and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A = 0.80, 95% CI [0.57, 1.02]; A = 0.80 [0.55, 1.04]) and twins concordant for having ASD (A = 0.71 [0.33, 1.09]; A = 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD because Twin-Pair Difference-Score analysis indicated that genetic factors may have contributed to ∼40% to 50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD; for example, our analyses suggested that unique environmental factors may have contributed to ∼10% to 20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule., Conclusion: White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted and they participated in the data collection, design, analysis, and/or interpretation of the work., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Autotransfusion following vaginal delivery has not been as widely adopted and existing data on this topic are limited to small case series., Methods: This is a single-center retrospective matched cohort study. Deliveries exposed to autotransfusion during obstetric hemorrhage were matched to unexposed controls with obstetric hemorrhage who did not receive autotransfusion. The primary outcome was allogeneic transfusion of packed red blood cells. Planned secondary analyses included change in hemoglobin following delivery, composite maternal safety outcomes, and unplanned postpartum health care utilization., Results: Thirty-six deliveries exposed to autotransfusion were matched to 144 unexposed controls. There was no significant difference in allogenic transfusion of packed red blood cells in the patients exposed to autotransfusion red with unexposed controls (adjusted OR 1.1; 95% CI 0.5-2.4). Deliveries that received autotransfusion had a less severe pre- to post-delivery decline in hemoglobin compared with unexposed controls across all values of QBL (p = .003). There were no significant differences in maternal morbidity outcomes evaluated in exposed versus unexposed deliveries., Conclusion: Autotransfusion in cases of vaginal obstetric hemorrhage did not attenuate rates of allogenic packed red blood cell transfusion but did result in a less severe pre- to postdelivery decline in hemoglobin at discharge. Autotransfusion cases did not have any markers of increased maternal morbidity when compared with a control group. These findings support emerging evidence indicating that autotransfusion of blood lost during vaginal obstetric hemorrhage is a safe and potentially effective tool for use in the management of obstetric hemorrhage., (© 2023 AABB.)

Objective: Individuals who deliver preterm are disproportionately affected by severe maternal morbidity. Limited data suggest that indicator-specific maternal morbidity varies by gestational age at delivery. We sought to evaluate the relationship between gestational age at delivery and the incidence of severe maternal morbidity and indicator-specific severe maternal morbidity., Methods: We used a hospital administrative delivery database to identify all singleton deliveries between 16 and 42 weeks gestation from 2002 to 2018. We defined severe maternal morbidity as the presence of any International Classification of Disease diagnosis or procedure codes outlined by the Centers for Disease Control and Prevention, intensive care unit admission, and/or prolonged postpartum hospital length of stay. Indicator-specific severe maternal morbidity was based on the diagnosis and procedure codes and was characterized across gestational age epochs. We categorized gestational age into three epochs to capture extremely preterm birth (less than 28 weeks gestation), preterm birth (28-36 weeks gestation) and term birth (37 weeks gestation and above). Multivariable binomial regression was used to assess the association between categories of gestational age at delivery and severe maternal morbidity adjusting for confounders including age, race, body mass index (BMI), insurance status, and preexisting hypertension or diabetes., Results: Severe maternal morbidity occurred in 2.5% of all deliveries. The unadjusted incidence of severe maternal morbidity by gestational age epoch was 12% at less than 28 weeks gestation, 8.4% at 28 to 36 weeks of gestation, and 1.7% at greater than or equal to 37 weeks gestation. After controlling for potential confounders the predicted probability of severe maternal morbidity was 16% (95% CI 14,17%) at 24 weeks compared to 2.2% (95% CI 2.1,2.3%) at 38 weeks. Sepsis, acute respiratory distress syndrome, mechanical ventilation, and shock were the most common diagnostic codes in deliveries less than 28 weeks gestation. Heart failure and cardiac arrhythmias were more common in patients with severe maternal morbidity delivering at term., Conclusion: A high proportion of severe maternal morbidity occurred in preterm patients, with the highest rates occurring at less than 28 weeks gestation. Individuals with severe maternal morbidity who deliver preterm had distinct indicators of morbidity compared to those who deliver at term.

Objective: Hemorrhage risk prediction tools were developed in response to rising rates of obstetric hemorrhage (OBH). The California Maternal Quality Care Collaborative (CMQCC) risk prediction tool classifies patients as low, medium, and high risk for OBH based on individual risk factors. At our institution, Magee-Womens Hospital (MWH), a unique OBH risk prediction tool was derived from the CMQCC tool that differs through its use of weighted risk factors and distinctive laboratory value cutoffs. Our objective is to compare this enhanced institution-specific tool to the CMQCC tool., Study Design: This study was a retrospective cohort analysis of delivery admissions from a single health care network. Admission OBH risk scores were assigned to each patient using both the MWH and CMQCC scores. Cohen's kappa estimated agreement. Scoring systems and maternal outcomes were compared using chi-square test. Composite morbidity included transfusion, hysterectomy, uterine artery embolization, and intensive care unit admission., Results: A total of 21,843 delivery admissions were included. A moderate association was observed between scoring systems (kappa = 0.41, p  < 0.001). The CMQCC tool categorized 16,184 (74%) patients as low risk, 4,664 (21%) as medium risk, and 995 (5%) as high risk. The MWH tool categorized 13,137 (60%) patients as low risk, 8,113 (37%) as medium risk, and 593 (3%) as high risk. The MWH score recategorized CMQCC low-risk patients to a higher stratum 26% of the time. CMQCC high-risk patients were recategorized to a lower stratum 82% of the time. Both the MWH and CMQCC tools were able to differentiate OBH-related morbidity across risk strata. The MWH tool independently predicted risk of composite morbidity within each stratum of the CMQCC score., Conclusion: Both the MWH and CMQCC tools independently distinguish risk of composite morbidity. Adding weighted values to individual risk factors further discriminates risk of morbidity. This suggests it may be reasonable to adapt the CMQCC tool to reflect institutional populations and resources., Key Points: · The nationally adopted CMQCC risk prediction tool identifies women at risk for obstetric hemorrhage.. · Our institution (MWH) developed a unique tool that weights individual risk factors to better capture risk.. · The CMQCC and MWH tools both differentiate risk; though similar to other tools, categorize a proportion of women who hemorrhage as low risk.., Competing Interests: H.N.S. reports other from Naima Health, LLC, grants from NIH, grants from CDC, grants from RK Mellon Foundation, outside the submitted work; F.M.H., J.M.P., and L.S.L. reported no conflict of interest., (Thieme. All rights reserved.)

N-glycanase 1 (NGLY1) deficiency is a debilitating, ultra-rare autosomal recessive disorder caused by loss of function of NGLY1, a cytosolic enzyme that deglycosylates other proteins. It is characterized by severe global developmental delay and/or intellectual disability, hyperkinetic movement disorder, transient elevation of transaminases, (hypo)alacrima and progressive, diffuse, length-dependent sensorimotor polyneuropathy. A prospective natural history study (NHS) was conducted to elucidate clinical features and disease course. Twenty-nine participants were enrolled (15 onsite, 14 remotely) and followed for up to 32 months, representing ~29% of the ~100 patients identified worldwide. Participants exhibited profound developmental delays, with almost all developmental quotients below 20 on the Mullen Scales of Early Learning, well below the normative score of 100. Increased difficulties with sitting and standing suggested decline in motor function over time. Most patients presented with (hypo)alacrima and reduced sweat response. Pediatric quality of life was poor except for emotional function. Language/communication and motor skill problems including hand use were reported by caregivers as the most bothersome symptoms. Levels of the substrate biomarker, GlcNAc-Asn (aspartylglucosamine; GNA), were consistently elevated in all participants over time, independent of age. Liver enzymes were elevated for some participants but improved especially in younger patients and did not reach levels indicating severe liver disease. Three participants died during the study period. Data from this NHS informs selection of endpoints and assessments for future clinical trials for NGLY1 deficiency interventions. Potential endpoints include GNA biomarker levels, neurocognitive assessments, autonomic and motor function (particularly hand use), (hypo)alacrima and quality of life., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Preterm infants experience multiple stressors including periodic neonatal hypoxia, maternal/caregiver separation, and acute pain from clinical procedures. Although neonatal hypoxia or interventional pain are associated with sexually dimorphic effects that may last into adulthood, the interaction of these common preterm stressors and caffeine pretreatment remains unknown. We hypothesize that an interaction of acute neonatal hypoxia, isolation, and pain modeling the experience of the preterm infant will augment the acute stress response and that caffeine routinely given to preterm infants will alter this response. Male and female rat pups were isolated and exposed to six cycles of periodic hypoxia (10% O 2 ) or normoxia (room air control) and/or intermittent pain by administering needle pricks (or touch control) to the paw on postnatal ( PD ) days 1-4 . An additional set of rat pups was pretreated with caffeine citrate (80 mg/kg ip) and studied on PD1 . Plasma corticosterone, fasting glucose, and insulin were measured to calculate homeostatic model assessment for insulin resistance (HOMA-IR) (index of insulin resistance). Glucocorticoid-, insulin-, and caffeine-sensitive gene mRNAs were analyzed in the PD1 liver and hypothalamus to evaluate downstream markers of glucocorticoid action. Acute pain with periodic hypoxia led to a large increase in plasma corticosterone, which was attenuated by pretreatment with caffeine. Pain with periodic hypoxia led to a 10-fold increase in hepatic Per1 mRNA expression in males, which was attenuated with caffeine. The augmentation of corticosterone and HOMA-IR at PD1 after periodic hypoxia with pain suggests early intervention to attenuate the stress response may mitigate the programming effects of neonatal stress.

Background: Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS., Methods: Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10., Results: A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R 2  = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development., Conclusions: Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed., Impact: Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs. We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years. We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years. This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Emotional prosody provides acoustical cues that reflect a communication partner's emotional state and is crucial for successful social interactions. Many children with autism have deficits in recognizing emotions from voices; however, the neural basis for these impairments is unknown. We examined brain circuit features underlying emotional prosody processing deficits and their relationship to clinical symptoms of autism., Methods: We used an event-related functional magnetic resonance imaging task to measure neural activity and connectivity during processing of sad and happy emotional prosody and neutral speech in 22 children with autism and 21 matched control children (7-12 years old). We employed functional connectivity analyses to test competing theoretical accounts that attribute emotional prosody impairments to either sensory processing deficits in auditory cortex or theory of mind deficits instantiated in the temporoparietal junction (TPJ)., Results: Children with autism showed specific behavioral impairments for recognizing emotions from voices. They also showed aberrant functional connectivity between voice-sensitive auditory cortex and the bilateral TPJ during emotional prosody processing. Neural activity in the bilateral TPJ during processing of both sad and happy emotional prosody stimuli was associated with social communication impairments in children with autism. In contrast, activity and decoding of emotional prosody in auditory cortex was comparable between autism and control groups and did not predict social communication impairments., Conclusions: Our findings support a social-cognitive deficit model of autism by identifying a role for TPJ dysfunction during emotional prosody processing. Our study underscores the importance of tuning in to vocal-emotional cues for building social connections in children with autism., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to provide initial validation of the Dimensional Assessment of Restricted and Repetitive Behaviors (DARB), a new parent-report measure designed to capture the full range of key restricted and repetitive behaviors (RRB) subdomains., Method: Parents of 1,892 children and adolescents with autism spectrum disorder (mean [SD] age = 10.81 [4.14] years) recruited from the SPARK (Simons Foundation Powering Autism Research for Knowledge) research match completed the DARB, several existing RRB instruments, and measures of social and communication impairments and anxiety. A subsample of 450 parents completed the DARB after 2 weeks to evaluate the test-retest stability., Results: Exploratory graph analysis conducted in the exploratory subsample identified 8 dimensions that were aligned with hypothesized RRB subdomains: repetitive sensory motor behaviors, insistence on sameness, restricted interests, unusual interests, sensory sensitivity, self-injurious behaviors, obsessions and compulsive behaviors, and repetitive language. The confirmatory application of the exploratory structural equation modeling conducted in the confirmatory subsample showed that the derived factor structure had a good fit to the data. Derived factors had excellent reliability, convergent and divergent validity, and very strong test-retest stability and showed a distinct pattern of associations with key demographic, cognitive and clinical correlates., Conclusion: The DARB will be useful in a variety of research and clinical contexts considering the prominence and clinical impact of RRB in autism spectrum disorder. Strong preliminary evidence indicates that the new scale is comprehensive and captures a wide range of distinct RRB subdomains not simultaneously captured by any of the existing instruments., (Copyright © 2023. Published by Elsevier Inc.)

Obstetrical hemorrhage is the leading cause of maternal morbidity and mortality worldwide, and the rates of severe hemorrhage are increasing. There is a crucial need to expand treatment options for hemorrhage to address this global crisis. Over the last decade, the evolution of hemorrhage control devices has contributed to advancements in obstetrical hemorrhage management. The number of existing hemorrhage control devices and techniques has increased markedly in recent years, and new devices are in development. The current evidence for established and investigational hemorrhage control devices has been summarized in this review. Of note, 2 main categories of devices exist: traditional uterine tamponade and vacuum-induced uterine tamponade. Although traditional intrauterine balloon tamponade devices are currently used widely in postpartum hemorrhage management, novel hemorrhage control devices and techniques have been developed. These include the minisponge tamponade device, the Jada System, a modified Bakri balloon technique, and a suction tube uterine tamponade technique. Reassuring safety data and preliminary efficacy data from pilot studies of these novel techniques support the powerful role intrauterine devices can play in obstetrical hemorrhage management. This review aimed to improve awareness of device options so that continued efforts can be made to integrate new technology into hemorrhage management protocols. Well-designed studies inclusive of new hemorrhage control devices are essential to understanding where new technology fits into preexisting obstetrical hemorrhage algorithms. In addition, access to new tamponade technology remains limited on a global scale. Programs aimed at both increasing access to devices and expanding educational initiatives are essential to make new technology a standard component for hemorrhage management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hemorrhage anticipation and management has shifted significantly over the past decade due to evolution of data surrounding management of obstetric hemorrhage. Limited data exists which describe the practical use and clinical application of hemorrhage management. Our goal was to identify obstetric hemorrhage management patterns in a cohort of practicing Maternal Fetal Medicine physicians., Methods: We administered a survey to Maternal Fetal Medicine (MFM) fellows and faculty that addressed the management of hemorrhage including risk assessment, uterotonic use, antifibrinolytic use, cell saver use, and abnormal placentation management. An email was sent out regarding the survey to a listserv of all Maternal Fetal Medicine fellow program coordinators to disseminate to their faculty and fellows. Eighty responses were obtained., Results: A total of 78 surveys were analyzed. Participants preferred methylergonovine as a first line agent (n = 57; 73%, n = 62; 80%). Most participants would consider using cell salvage when also activating MTP (28, 48%) or during scheduled deliveries who are high risk of hemorrhage (40, 69%). Approximately a third of providers would use TXA (tranexamic acid) prophylactically (n = 21; 28%). Only 26% of MFM fellows felt comfortable performing cesarean hysterectomy without Gynecologic Oncology., Conclusion: In comparison to prior reports, TXA use has increased substantially. Further, when looking at the management of abnormal placentation, the use of magnetic resonance imaging and embolization have both increased. Possibly due to the rise in centers of excellence for treatment of accreta spectrum disorders, Maternal Fetal Medicine fellows still feel largely unprepared to perform a cesarean hysterectomy without Gynecologic Oncology.

Background: Pelvic floor dysfunction is a group of disorders that can significantly impact quality of life due to persistent urinary and anal incontinence. Data evaluating the effect of prolonged second stage of labor and postpartum pelvic floor dysfunction is heterogenous and limited., Objective: To evaluate whether extending the length of labor in nulliparous women with prolonged second stage affects the presence of self-reported pelvic floor dysfunction after a randomized controlled trial of prolonged second stage., Study Design: We conducted a planned follow up survey to our randomized controlled trial of prolonged second stage of labor using the Pelvic Floor Distress Inventory-20 (PFDI-20). The primary outcome was the PFDI-20 summary score. Secondary outcomes included urinary and fecal incontinence, prolapse, and patient satisfaction. Women surveyed were nulliparous patients with epidural anesthesia, previously enrolled in a randomized controlled trial that assigned them to extended labor , at least 1 additional hour in the second stage if they were undelivered after three hours, or to usual labor , defined as expedited delivery after three hours in the second stage. Women were surveyed at 12 - 36 months postpartum., Results: Thirty-four of the seventy-eight women responded to the survey (43.6%). 17 women (50.0%) were from the extended labor group and 17 from the usual labor group (50.0%). Maternal demographic data were not significantly different between groups. The PFDI-20 summary score was 13.8 ± 23.3 in the extended labor group and 13.1 ± 20.9 in the usual labor group ( p  = 0.9). The Pelvic Organ Prolapse Distress Inventory-6 was 1.2 ± 2.9 in the extended labor group and 2.7 ± 6.4 in the usual labor group ( p  = 0.4). The Colorectal-Anal Distress Inventory-8 was 0.8 ± 2.8 in the extended labor group and 2.1 ± 4.0 in the usual labor group ( p  = 0.6). The Urinary Distress Inventory-6 was 11.8 ± 21.1 in the extended labor group and 8.3 ± 14.5 in the usual labor group ( p  = 0.6). Maternal and neonatal outcomes, as well as patient satisfaction, were not statistically significantly different between groups., Conclusion: Extending the length of labor in nulliparas with singleton gestations, epidural anesthesia, and prolonged second stage did not have an impact on PFDI-20 scores at 12-36 months postpartum. However, our study was underpowered to detect small, but potentially clinically important, differences., Clinical Trial Number: NCT02101515 (Study Registration Date March 28, 2014) https://clinicaltrials.gov/ct2/show/NCT02101515.

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes of abnormally long, vacant staring with low-frequency oscillations here termed vacant, perturbed consciousness (VPC). DBS modulated VPC likelihood in a frequency-specific manner. VPC events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), proposed indices of consciousness, and substantial changes to communication in CST circuits. During VPC, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of VPC and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method-but at different stimulation frequencies-can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of other consciousness disorders., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.R. is a consultant for and receives funding from Medtronic. The other authors declare no competing interests.

In Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal "SHIELD: Target, Test, and Tell" program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance. In Fall 2020, we performed >1,000,000 covidSHIELD tests, positivity rates remained low, we had zero COVID-19-related hospitalizations or deaths amongst our university community, and mortality in the surrounding Champaign County was reduced more than 4-fold relative to expected. This case study shows that fast/frequent testing and other interventions mitigated transmission of SARS-CoV-2 at a large public university., (© 2022. The Author(s).)

Background: Obstetric hemorrhage is a leading cause of preventable maternal mortality. To combat this, obstetric organizations worldwide recommend consideration of autotransfusion during severe peripartum bleeding to minimize allogenic transfusion. Current guidelines for autotransfusion in obstetrics are limited to patients undergoing cesarean birth. At present, women experiencing vaginal obstetric hemorrhage are excluded from many obstetric autotransfusion protocols. However, emerging data suggest that autotransfusion of vaginally shed blood is both safe and feasible in the obstetric patient population., Methods and Materials: In this review, we will provide an overview of the current literature surrounding cell salvage of vaginally send blood and a detailed outline of our institution's blood collection protocol., Results: Recent data suggests autotransfusion of vaginally shed blood is both safe and effective., Discussion: Implementation of autotransfusion technology into the delivery room is a critical next step for the advancement of transfusion medicine in obstetrics. This review provides an overview of the data surrounding autotransfusion of vaginally shed blood during maternal hemorrhage and describes practical suggestions for how it can be effectively implemented into routine practice., (© 2022 AABB.)