Role of Semaphorin 3A in common psychiatric illnesses such as schizophrenia, depression, and anxiety.

With societal development and an ageing population, psychiatric disorders have become a common cause of severe and long-term disability and socioeconomic burdens worldwide. Semaphorin 3A (Sema-3A) is a secreted glycoprotein belonging to the semaphorin family. Sema-3A is well known as an axon guidance factor in the neuronal system and a potent immunoregulator at all stages of the immune response. It is reported to have various biological functions and is involved in many human diseases, including autoimmune diseases, angiocardiopathy, osteoporosis, and tumorigenesis. The signals of sema-3A involved in the pathogenesis of these conditions, are transduced through its cognate receptors and diverse downstream signalling pathways. An increasing number of studies show that sema-3A plays important roles in synaptic and dendritic development, which are closely associated with the pathophysiological mechanisms of psychiatric disorders, including schizophrenia, depression, and autism, suggesting the involvement of sema-3A in the pathogenesis of mental diseases. This indicates that mutations in sema-3A and alterations in its receptors and signalling may compromise neurodevelopment and predispose patients to these disorders. However, the role of sema-3A in psychiatric disorders, particularly in regulating neurodevelopment, remains elusive. In this review, we summarise the recent progress in understanding sema-3A in the pathogenesis of mental diseases and highlight sema-3A as a potential target for the prevention and treatment of these diseases.

Screening for Chlamydia and Gonorrhea in Youth Correctional Facilities, Utah, USA.

We reviewed data obtained in October 2021-May 2023 from youth who reported a history of sexual activity upon admission to 1 of 12 juvenile justice facilities in Utah, USA, that offered screening for Chlamydia trachomatis and Neisseria gonorrhoeae. Urinalysis revealed C. trachomatis positivity of 10.77%, N. gonorrhoeae positivity of 1.08%, and coinfection C. trachomatis N. gonorrhoeae) of 0.90%. Prevalence of infection was similar for youths in rural and urban facilities. A total of 12.01% of those identifying as male and 14.01% of those identifying as female tested positive for C. trachomatis, N. gonorrhoeae, or coinfection. Of young adults who tested positive, 74.65% received their results while incarcerated, all of whom accepted treatment. Our research underscores the feasibility of providing prompt C. trachomatis/N. gonorrhoeae screening and treatment in juvenile correctional facilities. The pervasiveness of infection emphasizes the urgent need for early identification and treatment for C. trachomatis and N. gonorrhoeae in incarcerated youth nationwide.

Silencing FUT4 Inhibits the Progression of Osteosarcoma through Activation of FOXO1.

BACKGROUND: It has been reported that inhibition of Fucosyltransferase4 (FUT4) to activate Forkhead box O1 (FOXO1) can lead to apoptosis of cancer cells, however, the mechanism in osteosarcoma is still unclear. OBJECTIVE: To explore the biological significance of the connection between FUT4 and FOXO1 in osteosarcoma growth. METHODS: In vitro tests were conducted using the human osteoblast cell line and the osteosarcoma cell lines. QRT-PCR assay as well as western blot assay were used to ascertain the relative expression levels of FUT4 and FOXO1 in the cells. By using the CCK-8 assay, colony assay, EDU assay, wound healing assay and Transwell assay, osteosarcoma cells' ability to proliferate, migrate and invade were examined in relation to si- FUT4. TUNEL test was used to evaluate Si-impact FUT4's on KHOS and U2OS apoptosis in osteosarcoma cells. Western blot assay was used to identify the expression of proliferative, migrating and apoptosis-related protein markers in osteosarcoma cells KHOS and U2OS and the expression of important proteins in the Wnt/ ß-catenin signaling pathway. RESULTS: In comparison with osteoblasts, osteosarcoma cells expressed more FUT4. The osteosarcoma cells' capacities to proliferate, invade, and migrate were markedly inhibited by the inhibition of FUT4 expression, which also increased osteosarcoma cell apoptosis. The Wnt/ß-catenin signaling pathway was blocked by upregulating FOXO1 expression, which was in turn inhibited by inhibiting FUT4 expression. CONCLUSION: Osteosarcoma cells express more FUT4. The Wnt/ß-catenin signaling pathway has a significant effect on osteosarcoma cell death, and inhibition of FUT4 expression may target FOXO1 activation to decrease osteosarcoma cells' ability to proliferate, invade, and migrate.

MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice.

BACKGROUND: Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far. METHODS: We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3ß/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3ß/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice. RESULTS: Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice. CONCLUSIONS: These findings indicated that hippocampal miR-182-5p/Akt/GSK3ß/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.

Pelvic Floor Support and Symptoms 1 Year Postpartum in Relation to Excess Body Habitus Before, During and After First Vaginal Birth.

IMPORTANCE: Obesity may be a modifiable risk factor for pelvic floor disorders. OBJECTIVES: The objective of this study is to determine associations between weight, weight changes, and cumulative exposure to excess body mass index (BMI) from prepregnancy to 1 year postpartum on pelvic floor support and symptoms 1 year after first vaginal birth. STUDY DESIGN: In 645 primiparous women who gave birth vaginally, we assessed anatomic pelvic floor support, pelvic floor symptoms and BMI at the third trimester, 5 - 10 weeks, and 1 year postpartum; we also assessed BMI prepregnancy and predelivery. Using multivariable models, we determined associations between pelvic floor outcomes 1 year postpartum and BMI quartiles at different timepoints, gestational weight gain, and postpartum weight retention. We evaluated associations between stress urinary incontinence (SUI) and moderate/severe urinary incontinence (UI) 1 year postpartum and cumulative excess BMI from prepregnancy to 1-year postpartum (BMI1year). RESULTS: Body mass index was not associated with anatomic support, composite symptom burden, overactive bladder, anal incontinence, or constipation at any timepoint. Gestational weight gain and postpartum weight retention were not associated with any 1-year outcome. Body mass index at every timepoint was positively associated with SUI and moderate/severe UI; BMI1year was most predictive. Cumulative excess BMI was positively associated with SUI and moderate/severe UI but only slightly more predictive of these outcomes than BMI1year alone. CONCLUSIONS: Body mass index over the pregnancy trajectory was not associated with outcomes other than UI. The small advantage of cumulative exposure to excess BMI over BMI1year in predicting SUI and moderate/severe UI suggests that BMI1year adequately captures risk of these 1-year outcomes.

Down-regulation of miR-18b-5p protects against splenic hemorrhagic shock by directly targeting HIF-1α/iNOS pathway.

Splenic hemorrhagic shock is a typical emergency in surgery, seriously threatening human beings' life. Emerging evidence shows that microRNAs (miRNAs) are closely related to inflammation and immunity in the body. However, the detailed effects and underlying mechanisms of miRNAs on the immune function of splenic hemorrhagic shock have not been revealed yet. In the present study, we construct the rat hemorrhagic shock model, and the rats are further cured with splenic blood transport clipping recanalization (SBTCR). MiR-18b-5p was highly expressed in the spleen of hemorrhagic shock rats detected by the qRT-PCR assay. Functionally, down-regulation of miR-18b-5p notably inhibited the levels of SOD1, iNOS and IL-6 in macrophages isolated from splenic tissues detected by qRT-PCR and ELISA assays. In addition, inhibition of miR-18b-5p significantly decreased the M1/M2 ratio of macrophages. Besides, knockdown of miR-18b-5p obviously reduced the Th1/Th2 ratio of CD4+ T cells. Moreover, HIF-1α was predicted as a target gene of miR-18b-5p, which was further confirmed by dual-luciferase reporter assay, and HIF-1α was negatively associated with miR-18b-5p. Furthermore, overexpression of HIF-1α partially restored the effects of miR-18b-3p on inflammation and immunity in macrophages. Taken together, miR-18b-5p may be a novel therapeutic candidate target in splenic hemorrhagic shock treatment.

Relative and Maximal Intra-abdominal Pressure and Postpartum Pelvic Floor Outcomes in Primiparas Delivered Vaginally.

OBJECTIVES: This study aimed to explore associations between relative and maximal intra-abdominal pressure (IAP) on pelvic floor outcomes in primiparas delivered vaginally. METHODS: At 5-10 weeks and 1 year postpartum, we measured absolute IAP by vaginal sensor while participants lifted a weighted car seat (IAPLIFT) and performed isometric trunk flexion endurance (IAPTFE) and seated maximal strain (IAPSTRAIN). Primary outcomes, completed 1 year postpartum, included worse pelvic floor support (descent to or beyond the hymen) and positive symptom burden (bothersome symptoms in ≥2 of 6 domains on the Epidemiology of Prolapse and Incontinence Questionnaire). We calculated relative IAP (as absolute IAP/IAPSTRAIN). RESULTS: Of 542 participants, 9.7% demonstrated worse support and 54.3% demonstrated symptom burden at 1 year postpartum. In multivariable analyses, absolute IAPLIFT and absolute IAPTFE at 5-10 weeks postpartum were not associated with worse support. As relative IAP at 5-10 weeks increased, the prevalence of worse support decreased (prevalence ratio [PR] of 0.77 [95% confidence intervals (CIs), 0.63-0.94] and PR of 0.79 [95% CI, 0.67-0.93]) per 10% increase for relative IAPLIFT and relative IAPTFE, respectively. This was largely due to IAPSTRAIN, which increased the prevalence of worse support (PR, 1.15 [95% CI, 1.06-1.25]) per 10 cm H2O increase. One year postpartum, only IAPSTRAIN increased the prevalence of worse support (PR, 1.11 [95% CI, 1.02-1.20]) per 10 cm H2O. Of all IAP measures at both time points, only absolute IAPLIFT at 1 year significantly increased the prevalence of symptom burden (PR, 1.11 [95% CI, 1.05-1.18]) per 10 cm H2O. CONCLUSIONS: This exploratory analysis suggests that postpartum IAPSTRAIN may increase the prevalence of worse support in primiparas delivered vaginally.

Do Measures of Muscular Fitness Modify the Effect of Intra-abdominal Pressure on Pelvic Floor Support in Postpartum Women?

OBJECTIVE: This study aimed to determine whether measures of muscular fitness modify the effect of intra-abdominal pressure (IAP) during lifting on pelvic floor support. METHODS: Participants, primiparous women 1 year after vaginal delivery, underwent the Pelvic Organ Prolapse Quantification examination, measurement of IAP via a vaginal sensor while lifting a weighted car seat, pelvic floor muscle force assessment using an instrumented speculum, grip strength using a hand dynamometer, and trunk flexor endurance by holding an isometric contraction while maintaining a 60-degree angle to the table. We dichotomized pelvic floor support as worse (greatest descent of the anterior, posterior, or apical vagina during maximal strain at or below the hymen) versus better (all points above the hymen). RESULTS: Of 825 participants eligible after delivery, 593 (71.9%) completed a 1-year study visit. Mean (SD) age was 29.6 (5.0) years. One year postpartum, 55 (9.3%) demonstrated worse support. There were no differences in IAP during lifting or in other measures of pelvic floor loading between women with better and worse support. In multivariable analyses, neither grip strength nor pelvic floor muscle force modified the effect of IAP on support. In women with trunk flexor endurance duration ≥13 minutes, the odds of worse support increased significantly as IAP increased. No fitness measure modified the effect of other measures of pelvic floor loading on support. CONCLUSIONS: Primiparous women with higher IAP during lifting and greater muscular fitness did not have reduced odds of worse pelvic floor support compared with those with lower IAP at the same muscular fitness.

Association Between Measures of Trunk Recovery 5 to 10 Weeks Postpartum and Pelvic Floor Support and Symptoms 1 Year Postpartum in Primiparas Delivered Vaginally.

OBJECTIVE: To determine whether 2 aspects of trunk recovery after childbirth, intraabdominal pressure (IAP) generation and trunk flexor endurance (TFE), predict measures of pelvic floor health 1 year postpartum. METHODS: In this prospective cohort study, we enrolled nulliparas in their third trimester and followed up those delivered vaginally for 1 year. We measured IAP while lifting a weighted car seat (IAPLIFT), IAP during TFE testing (IAPTFE), and TFE duration 5 to 10 weeks postpartum and assessed pelvic floor support and symptoms 1 year postpartum. RESULTS: Mean age of the 624 participants was 28.7 years. At 5 to 10 weeks postpartum, mean (SD) maximal IAPLIFT and IAPTFE were 47.67 (11.13) and 51.57 (12.34) cm H2O, respectively. Median TFE duration was 126 seconds (Interquartile range, 74-211). At 1 year postpartum, 9.3% demonstrated worse support (maximal vaginal descent at or below hymen) and 54% met criteria for symptom burden (bothersome symptoms in ≥2 domains of Epidemiology of Prolapse and Incontinence Questionnaire). In multivariable models, neither IAPLIFT nor IAPTFE were associated with worse support or symptom burden (P = 0.54-1.00). Trunk flexor endurance duration increased prevalence of worse support (prevalence ratio, 1.05; 95% confidence interval, 1.01-1.08) per 60-second increase, P = 0.005) but not symptom burden (prevalence ratio, 1.00; 95% confidence interval, 0.98-1.03; P = 0.92). CONCLUSIONS: These results provide some reassurance to early postpartum women, who are unlikely to perform routine activities that generate IAP far outside the range tested. Further research is needed to understand why women with long TFE durations have increased prevalence of worse support.

Factors That Contribute to Cost Differences Based on ICU of Admission in Neonates Undergoing Congenital Heart Surgery: A Novel Decomposition Analysis.

OBJECTIVES: We leveraged decomposition analysis, commonly used in labor economics, to understand determinants of cost differences related to location of admission in children undergoing neonatal congenital heart surgery. DESIGN: A retrospective cohort study. SETTING: Pediatric Health Information Systems database. PATIENTS: Neonates (<30 d old) undergoing their index congenital heart surgery between 2004 and 2013. MEASUREMENTS AND MAIN RESULTS: A decomposition analysis with bootstrapping determined characteristic (explainable by differing covariate levels) and structural effects (if covariates are held constant) related to cost differences. Covariates included center volume, age at admission, prematurity, sex, race, genetic or major noncardiac abnormality, Risk Adjustment for Congenital Heart Surgery-1 score, payor, admission year, cardiac arrest, infection, and delayed sternal closure.Of 19,984 infants included (10,491 [52%] to cardiac ICU/PICU and 9,493 [48%] to neonatal ICU), admission to the neonatal ICU had overall higher average costs ($24,959 ± $3,260; p < 0.001) versus cardiac ICU/PICU admission. Characteristic effects accounted for higher costs in the neonatal ICU ($28,958 ± $2,044; p < 0.001). Differing levels of prematurity, genetic syndromes, hospital volume, age at admission, and infection contributed to higher neonatal ICU costs, with infection rate providing the most significant contribution ($13,581; p < 0.001). Aggregate structural effects were not associated with cost differences for those admitted to the neonatal ICU versus cardiac ICU/PICU (p = 0.1). Individually, prematurity and age at admission were associated with higher costs due to structural effects for infants admitted to the neonatal ICU versus cardiac ICU/PICU. CONCLUSIONS: The difference in cost between neonatal ICU and cardiac ICU/PICU admissions is largely driven by differing prevalence of risk factors between these units. Infection rate was a modifiable factor that accounted for the largest difference in costs between admitting units.

Ophiopogonin A Alleviates Hemorrhagic Shock-Induced Renal Injury via Induction of Nrf2 Expression.

Ophiopogonin, including Ophiopogonin A, B, C, D, is an effective active component of traditional Chinese medicine Ophiopogon japonicus which has a wide range of pharmacological effects such as protecting myocardial ischemia, resisting myocardial infarction, immune regulation, lowering blood glucose, and anti-tumor. However, the functions of ophiopogonin A on hemorrhagic shock (HS)-induced renal injury remain unclear. First, this study constructed an HS rat model and hypoxia HK-2 cell model to assess the effects of ophiopogonin A in vivo and in vitro. In vivo, HE and TUNEL staining show that ophiopogonin A dose-dependently inhibits HS-induced tissue damage and apoptosis. Moreover, ophiopogonin A dose-dependently downregulates the levels of blood urea nitrogen (BUN), creatinine (Cr), KIM-1, NGAL, iNOS, TNF-α, IL-1ß, and IL-6 in HS rats kidney tissues, and decreases the number of MPO-positive cells. In vitro, we get similar results that ophiopogonin A dose-dependently improves hypoxia-induced HK-2 cell apoptosis and damage. In addition, ophiopogonin A dose-dependently increases the expression of NF E2-related factor 2 (Nrf2), while knockdown of Nrf2 reverses the functions of ophiopogonin A in vivo and in vitro. Furthermore, ophiopogonin A dose-dependently promotes the phosphorylation of ERK in HS kidney tissues and hypoxia-treated HK-2 cells, suggesting that ophiopogonin A functions via the p-ERK/ERK signaling pathway.

Barriers to Sonographer Screening for Fetal Heart Defects: A U.S. National Survey.

OBJECTIVE: We surveyed obstetric sonographers, who are at the forefront of the screening process to determine how barriers to prenatal cardiac screening impacted screening abilities. METHODS: We performed a cross-sectional national survey of obstetric sonographers in the United States using a sampling frame from American Registry of Diagnostic Medical Sonography mailing lists. The web survey measured the ability to obtain and interpret fetal heart images. Several cognitive, sociodemographic, and system-level factors were measured, including intention to perform cardiac imaging. Regression and mediation analyses determined factors associated with intention to perform and ability to obtain and interpret cardiac images. Subgroup analyses of sonographers in tertiary versus nontertiary centers were also performed. RESULTS: Survey response rate either due to noncontact or nonresponse was 40%. Of 480 eligible sonographers, ~30% practiced in tertiary settings. Sonographers had lower intention to perform outflow views compared to 4 chambers. Higher self-efficacy and professional expectations predicted higher odds of intention to perform outflow views (OR 2.8, 95% CI 1.9-4.2 and 1.9, 95% CI 1.1-3.0, respectively). Overall accuracy of image interpretation was 65% (±14%). For the overall cohort and nontertiary subgroup, higher intention to perform outflows was associated with increased accuracy in overall image interpretation. For the tertiary subgroup, self-efficacy and feedback were strongly associated with accuracy. CONCLUSIONS: We identified several modifiable (some heretofore unrecognized) targets to improve prenatal cardiac screening. Priorities identified by sonographers that are associated with screening success should guide future interventions.

The Association Between Pelvic Floor Muscle Force and General Strength and Fitness in Postpartum Women.

OBJECTIVE: The aim of the study was to determine whether measures of muscular strength and fitness are associated with pelvic floor muscle (PFM) force 1-year postpartum in a population of primiparous women who delivered vaginally. METHODS: This cross-sectional analysis is an ancillary study to an ongoing prospective cohort study and includes 203 primiparous women. Procedures collected 1-year postpartum included maximal PFM force, grip strength, trunk flexor muscle endurance, percent body fat, intra-abdominal pressure during trunk flexor endurance testing, intra-abdominal pressure during strain, and self-reported physical activity. RESULTS: The mean (SD) age was 29.8 (5.0) years and the mean (SD) body mass index was 24.5 (5.2) kg/m. Nineteen percent were of Hispanic ethnicity. The median (interquartile range) PFM force was 5.05 (2.86-7.94) N. The median (interquartile range) trunk flexor endurance time was 146.0 (78.0-267.0), whereas the mean (SD) grip strength and percent fat were 32.4 (6.4) kg and 29.4% (10.0), respectively.There were no statistically significant associations between PFM force and any of the measures tested on analyses unadjusted or adjusted for self-report of doing PFM exercises. Of other factors evaluated, non-Hispanic ethnicity, increasing age, self-reported family history of pelvic organ prolapse or urinary incontinence, and normal and obese body mass index (both compared with overweight) were associated with lower PFM force. CONCLUSIONS: In primiparous women 1-year postpartum, we found no associations between PFM force and measures of strength and fitness. This study's results are consistent with existing literature that specific, targeted, and consistent pelvic floor exercises are the best way to improve PFM strength.

Relationships Between Poor Health and Calories From Fat Among Commercial Truck Drivers.

OBJECTIVE: Commercial motor vehicle (CMV) drivers face many challenges to their health, including poor diet, disease, and crash risk. This study quantifies relationships between the percentage of calories from fat (PCF) and markers of poor health, many of which are associated with increased crash risk. METHODS: Cross-sectional data from 790 CMV drivers were analyzed. PCF were estimated using the National Cancer Institute Percentage Energy from Fat Screener. Adjusted odds ratios (ORs) were calculated. RESULTS: The highest category of PCF (>38.2%) was statistically significantly more likely to not exercise (OR = 2.08), have sleep apnea (OR = 2.31), snore (OR = 1.90), smoke (OR = 2.28), and use alcohol (OR = 1.87) after adjustments. CONCLUSION: Meaningful relationships between PCF and poor health indicators exist. These indicators may provide an intervention to improve the health and safety of CMV drivers.

An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis.

Background: The single nucleotide polymorphism of the gene 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. Objective: We hypothesized that variability in this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers, confounders, or both, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates. Design: We systematically extracted from published studies the data on tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting metadata set was first used to analyze the covariates' modifying effect by meta-regression and other statistical means. Subsequently, we controlled for this modifying effect by genotype-stratifying tHcy data and analyzed the variability in the risk resulting from the confounding of covariates. Results: The data set contains data on 36 rs1801133 covariates that were collected from 114,799 participants and 256 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification as well as confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner. Conclusions: We showed an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public, who increasingly receive genetic data from commercial services without interpretation of its clinical relevance. This study was registered at Research Registry with the registration number reviewregistry328.

Neurobehavioral evaluation of neonates with congenital heart disease: a cohort study.

AIM: To describe neurobehavioral patterns in neonates with congenital heart disease (CHD). METHOD: A cohort study describing neurobehavioral performance of neonates with CHD requiring cardiac surgery. The neonates were evaluated preoperatively and postoperatively with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) and scores were compared with published normative values. Clinical factors were obtained by chart review to assess their association with behavior. The CHD NNNS score pattern was compared with previously reported profiles in other high-risk populations. RESULTS: NNNS evaluations were completed on 67 neonates with CHD, resulting in 97 evaluations (50 preoperative, 47 postoperative). Compared with normative values, the cohort with CHD demonstrated decreased attention, regulation, asymmetry, stress, arousal, and excitability, along with increased non-optimal reflexes, lethargy, and need for handling (p<0.05 for all). Additional clinical factors had a minimal effect on the neurobehavioral pattern. Compared with previously published patterns in high-risk neonates without CHD, the cohort with CHD demonstrated a unique pattern of behavior. INTERPRETATION: Neonates with CHD demonstrate different neurobehavioral performance compared with typically developing neonates born at term as well as other high-risk neonates. Our experience suggests there is a unique neonatal neurobehavioral pattern in the hospitalized population with CHD. Targeted neonatal neurobehavioral evaluations may be useful in developing specific therapies to improve neurodevelopmental outcomes in neonates with CHD. WHAT THIS PAPER ADDS: Neonates with congenital heart disease demonstrate different neurobehavioral performance than typically developing neonates. Evaluation of neonatal neurobehavioral performance provides an opportunity to identify neurodevelopmental variability early. Identification of neurobehavioral performance variability allows targeted interactions and therapy.

Digoxin Use in Infants with Single Ventricle Physiology: Secondary Analysis of the Pediatric Heart Network Infant Single Ventricle Trial Public Use Dataset.

Digoxin has been associated with reduced interstage mortality after Norwood procedure. We sought to determine its association with survival and change in weight-for-age Z-score (WAZ) before the superior cavopulmonary connection (SCPC) surgery and at 14 months in a heterogeneous group of single ventricle infants. We performed a post-hoc analysis of the Pediatric Heart Network Infant Single Ventricle public use dataset to determine associations between digoxin and survival, transplant-free survival, and change in WAZ pre-SCPC and at 14 months. Sub-analyses of survival and transplant-free survival were performed for subjects who underwent Damus-Kaye-Stansel (DKS)/Norwood. Propensity score weighting was used in Cox hazard-proportion models. Of 229 subjects, 82 (36%) received digoxin and 147 (64%) received no digoxin. Pre-SCPC and 14-month survival and transplant-free survival were not significantly different between the digoxin and no digoxin groups for the main cohort and DKS/Norwood sub-group. However, in DKS/Norwood subjects there was a trend towards improved interstage transplant-free survival in the digoxin group (95.7 vs. 89.6%, p = 0.08). Digoxin was associated with a greater decrease in WAZ from birth to pre-SCPC (- 1.96 ± 0.19 vs. - 1.31 ± 0.18, p < 0.001) and birth to 14 months (- 0.64 ± 0.15 vs. - 0.19 ± 0.15, p = 0.03). Digoxin was not associated with improved survival during the interstage or at 14 months in a mixed single ventricle cohort, but there was a trend towards improved interstage transplant-free survival in post-Norwood infants. As digoxin was associated with poorer weight gain, further research is needed to identify the risks/benefits for anatomic subtypes of infants with single ventricles.

Quantitative Ultrasound and Tibial Dysplasia in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with unilateral anterolateral bowing with subsequent fracture and nonunion. In infancy, physiologic bowing of the lower leg can be confused with pathologic tibial dysplasia in NF1. Little is known about the bone physiology of the tibiae prior to fracture or predictors of fracture. The aim of this study was to characterize bone quality of bowed tibiae prior to fracture in NF1 using quantitative ultrasound (QUS). Bone quality was assessed on both tibiae (the non-bowed and bowed tibiae) using QUS to measure speed of sound (SOS) at the mid-shaft in 23 individuals with NF1. SOS (m/s) was determined and Z-scores generated using cross-sectional reference data of the same sex and age. The mean difference in SOS Z-scores when comparing the bowed tibia vs the individual's contralateral unaffected tibia was statistically significant with lower mean Z-scores in the bowed tibia (p = 0.001). Radiographs of all individuals with a clinical diagnosis of anterolateral bowing were reviewed, and in 2 individuals the radiographs showed minimal bowing with absence of characteristic cortical thickening and medullary canal narrowing in NF1-related tibial dysplasia, suggesting physiologic bowing. In both individuals, the Z-scores of the bowed leg were not lower than the unaffected leg supporting the suggestion of physiologic bowing rather than pathologic tibial dysplasia. These data show that dysplastic tibiae in NF1 prior to fracture and nonunion have abnormal bone quality with significant decreases in SOS even though radiographically the tibiae show a thickened cortex. These data also suggest that QUS can help distinguish dysplastic bowing vs physiologic bowing in infancy in NF1. QUS is an effective quantitative outcome measure for trials aimed at improving tibial bowing to prevent fracture, and it is a potential aid in diagnosis and clinical management in NF1.

Variables Affecting Intra-abdominal Pressure During Lifting in the Early Postpartum Period.

OBJECTIVES: Intra-abdominal pressure (IAP) may contribute to pelvic floor health, although the direction and magnitude of such an effect, if any, are not yet known. Identifying individual characteristics, and in particular modifiable factors, associated with higher IAP during recovery from vaginal childbirth might serve to mitigate early pelvic floor dysfunction. The aim of this study was to identify characteristics associated with maximal IAP during lifting in postpartum primiparous women who delivered vaginally. METHODS: At 6 to 10 weeks postpartum, we measured maximal IAP, assessed via an upper vaginal sensor, as participants (enrolled in an ongoing cohort study) lifted a weighted car seat (12.5 kg). We evaluated whether the following independent variables were associated with maximal IAP: age, ethnicity, body mass index, height, abdominal circumference, weight gain during pregnancy, lifting time, breath holding during lifting, lifting technique, measures of muscular fitness, and days since delivery. RESULTS: In the 206 participants, weight, waist circumference, body mass index, and days since delivery were positively associated with mean maximal IAP during lifting, whereas IAP decreased as height increased. As the duration of the lifting task increased, mean maximal IAP during lifting also increased, but there were no associations between lifting technique or breath holding during lifting and IAP. Neither pelvic floor muscle strength nor abdominal muscle endurance was associated with IAP during lifting. CONCLUSIONS: Other than measures of body habitus and lifting duration, we did not identify modifiable factors that could mitigate maximal pressures experienced by the pelvic floor during the early postpartum period.

Platelet Inhibition in Shunted Infants on Aspirin at Short and Midterm Follow-Up.

There are few data to guide aspirin therapy to prevent shunt thrombosis in infants. We aimed to determine if aspirin administered at conventional dosing in shunted infants resulted in ≥50% arachidonic acid (AA) inhibition in short and midterm follow-up using thromboelastography with platelet mapping (TEG-PM) and to describe bleeding and thrombotic events during follow-up. We performed a prospective observational study of infants on aspirin following Norwood procedure, aortopulmonary shunt alone, or cavopulmonary shunt surgery. We obtained TEG-PM preoperatively, after the third dose of aspirin, at the first postoperative clinic visit, and 2-8 months after surgery. The primary outcome was the proportion of subjects with ≥50% AA inhibition on aspirin. All bleeding and thrombotic events were collected. Of 24 infants analyzed, 13% had ≥50% AA inhibition at all designated time points after aspirin initiation; 38% had ≥50% AA inhibition after the third aspirin dose of aspirin, 60% at the first postoperative clinic visit, and 26% 2-8 months after surgery. Bleeding events occurred in eight subjects, and two had a thrombotic event. Bleeding events were associated with greater AA inhibition just prior to starting aspirin (p = 0.02) and after the third dose of aspirin (p = 0.04), and greater ADP inhibition before surgery (p = 0.03). The majority of infants failed to consistently have ≥50% AA inhibition when checked longitudinally postoperatively. Preoperative TEG-PM may be useful in identifying infants at higher risk of bleeding events on aspirin in the early postoperative period. Further research is needed to guide antiplatelet therapy in this population.