Meta-regression of sulcal patterns, clinical and environmental factors on neurodevelopmental outcomes in participants with multiple CHD types.

Congenital heart disease affects 1% of infants and is associated with impaired neurodevelopment. Right- or left-sided sulcal features correlate with executive function among people with Tetralogy of Fallot or single ventricle congenital heart disease. Studies of multiple congenital heart disease types are needed to understand regional differences. Further, sulcal pattern has not been studied in people with d-transposition of the great arteries. Therefore, we assessed the relationship between sulcal pattern and executive function, general memory, and processing speed in a meta-regression of 247 participants with three congenital heart disease types (114 single ventricle, 92 d-transposition of the great arteries, and 41 Tetralogy of Fallot) and 94 participants without congenital heart disease. Higher right hemisphere sulcal pattern similarity was associated with improved executive function (Pearson r = 0.19, false discovery rate-adjusted P = 0.005), general memory (r = 0.15, false discovery rate P = 0.02), and processing speed (r = 0.17, false discovery rate P = 0.01) scores. These positive associations remained significant in for the d-transposition of the great arteries and Tetralogy of Fallot cohorts only in multivariable linear regression (estimated change ß = 0.7, false discovery rate P = 0.004; ß = 4.1, false discovery rate P = 0.03; and ß = 5.4, false discovery rate P = 0.003, respectively). Duration of deep hypothermic circulatory arrest was also associated with outcomes in the multivariate model and regression tree analysis. This suggests that sulcal pattern may provide an early biomarker for prediction of later neurocognitive challenges among people with congenital heart disease.

Spectral characterization of a blue light-emitting micro-LED platform on skin-associated microbial chromophores.

The therapeutic application of blue light (380 - 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin, termed the skin microbiome. In conditions including acne vulgaris, blue light is thought to address this imbalance through the selective photoexcitation of microbial species expressing wavelength-specific chromophores, differentially affecting skin commensals and thus altering the relative species composition. However, the abundance and diversity of these chromophores across the skin microbiota remains poorly understood. Similarly, devices utilised for studies are often bulky and poorly characterised which if translated to therapy could result in reduced patient compliance. Here, we present a clinically viable micro-LED illumination platform with peak emission 450 nm (17 nm FWHM) and adjustable irradiance output to a maximum 0.55 ± 0.01 W/cm2, dependent upon the concentration of titanium dioxide nanoparticles applied to an accompanying flexible light extraction substrate. Utilising spectrometry approaches, we characterised the abundance of prospective blue light chromophores across skin commensal bacteria isolated from healthy volunteers. Of the strains surveyed 62.5% exhibited absorption peaks within the blue light spectrum, evidencing expression of carotenoid pigments (18.8%, 420-483 nm; Micrococcus luteus, Kocuria spp.), porphyrins (12.5%, 402-413 nm; Cutibacterium spp.) and potential flavins (31.2%, 420-425 nm; Staphylococcus and Dermacoccus spp.). We also present evidence of the capacity of these species to diminish irradiance output when combined with the micro-LED platform and in turn how exposure to low-dose blue light causes shifts in observed absorbance spectra peaks. Collectively these findings highlight a crucial deficit in understanding how microbial chromophores might shape response to blue light and in turn evidence of a micro-LED illumination platform with potential for clinical applications.

Draft genome of the marine bacterium Alteromonas gracilis strain J4 isolated from the green coenocytic alga Caulerpa prolifera.

Here, we present the draft genome sequence of Alteromonas gracilis strain J4, isolated from the green macroalga Caulerpa prolifera. The draft genome is 4,492,914 bp in size and contains 4,719 coding DNA sequences, 67 tRNAs, and 16 rRNA-coding genes. Strain J4 may exhibit host growth-promoting properties.

LORIS robustly predicts patient outcomes with immune checkpoint blockade therapy using common clinical, pathologic and genomic features.

Despite the revolutionary impact of immune checkpoint blockade (ICB) in cancer treatment, accurately predicting patient responses remains challenging. Here, we analyzed a large dataset of 2,881 ICB-treated and 841 non-ICB-treated patients across 18 solid tumor types, encompassing a wide range of clinical, pathologic and genomic features. We developed a clinical score called LORIS (logistic regression-based immunotherapy-response score) using a six-feature logistic regression model. LORIS outperforms previous signatures in predicting ICB response and identifying responsive patients even with low tumor mutational burden or programmed cell death 1 ligand 1 expression. LORIS consistently predicts patient objective response and short-term and long-term survival across most cancer types. Moreover, LORIS showcases a near-monotonic relationship with ICB response probability and patient survival, enabling precise patient stratification. As an accurate, interpretable method using a few readily measurable features, LORIS may help improve clinical decision-making in precision medicine to maximize patient benefit. LORIS is available as an online tool at https://loris.ccr.cancer.gov/ .

Reduced Sialylation of Airway Mucin Impairs Mucus Transport by Altering the Biophysical Properties of Mucin.

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific α-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.

Advance Directives Change Frequently in Nursing Home Residents.

OBJECTIVES: To describe the rate, timing, and pattern of changes in advance directives (ADs) of do not resuscitate (DNR) and do not hospitalize (DNH) orders among new admissions to nursing homes (NHs). DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Admissions to all publicly funded NHs in Ontario, Canada, between January 1, 2013, and December 31, 2017. METHODS: Residents were followed until discharged from incident NH stay, death, or were still present at the end of study (December 31, 2019). They were categorized into 3 mutually exclusive baseline composite AD groups: Full Code, DNR Only, and DNR+DNH. We used Poisson regression models to estimate the incidence rate ratios of AD change between different AD groups and different decision makers for personal care, adjusted for baseline clinical and sociodemographic variables. RESULTS: A total of 102,541 NH residents were eligible for inclusion. Residents with at least 1 AD change accounted for 46% of Full Code, 30% of DNR Only, and 25% of DNR+DNH group. Median time to first AD change ranged between 26 and 55 weeks. For Full Code and DNR Only residents, the most frequent change was to an AD 1 level lower in aggressiveness or intervention, whereas for DNR+DNH residents the most frequent change was to DNR Only. About 16% of residents had 2 or more AD changes during their stay. After controlling for covariates, residents with a DNR-only order or DNR+DNH orders at admission and those with a surrogate decision maker were associated with lower AD change rates. CONCLUSIONS AND IMPLICATIONS: Measuring AD adherence rates that are documented only at a particular time often underestimates the dynamics of AD changes during a resident's stay and results in an inaccurate measure of the effectiveness of AD on resident care. There should be more frequent reviews of ADs as they are quite dynamic. Mandatory review after an acute change in a resident's health would ensure that ADs are current.

Design and synthesis of oxytocin glycosides for the treatment of pain and substance use disorder.

Peptide drugs are a promising alternative to classical small molecule therapeutics with diverse applications, ranging from antibiotic resistant infection to prostate cancer. Oxytocin (OT) is a highly evolutionarily conserved peptide neurohormone and has been of interest for pharmaceutical use since 1909. Despite their increased safety profile relative to most small molecule drugs, peptides are poor candidates based on the pharmacokinetic (PK) properties from their peptide nature. Broad application of OT as a drug has been limited by these same PK issues. Several strategies have been proposed to overcome these limitations, among them glycosylation, which was used in combination with other sequence modifications to produce robust antinociception in mouse models, increased selectivity and potency at the OT receptor, and improved stability in rats.

Short-term cold exposure induces persistent epigenomic memory in brown fat.

Deficiency of the epigenome modulator histone deacetylase 3 (HDAC3) in brown adipose tissue (BAT) impairs the ability of mice to survive in near-freezing temperatures. Here, we report that short-term exposure to mild cold temperature (STEMCT: 15°C for 24 h) averted lethal hypothermia of mice lacking HDAC3 in BAT (HDAC3 BAT KO) exposed to 4°C. STEMCT restored the induction of the thermogenic coactivator PGC-1α along with UCP1 at 22°C, which is greatly impaired in HDAC3-deficient BAT, and deletion of either UCP1 or PGC-1α prevented the protective effect of STEMCT. Remarkably, this protection lasted for up to 7 days. Transcriptional activator C/EBPß was induced by short-term cold exposure in mouse and human BAT and, uniquely, remained high for 7 days following STEMCT. Adeno-associated virus-mediated knockdown of BAT C/EBPß in HDAC3 BAT KO mice erased the persistent memory of STEMCT, revealing the existence of a C/EBPß-dependent and HDAC3-independent cold-adaptive epigenomic memory.

Kinase-catalyzed crosslinking: A comparison of ATP-crosslinker analogs.

Protein phosphorylation is catalyzed by kinases to regulate cellular events and disease states. Identifying kinase-substrate relationships represents a powerful strategy to understand cell biology and disease yet remains challenging due to the rapid dynamics of phosphorylation. Over the last decade, several γ-phosphoryl modified ATP analogs containing crosslinkers were developed to covalently conjugate kinases, their substrates, and their associated proteins for subsequent characterization. Here, kinetics and crosslinking experiments demonstrated that the UV-activated analogs, ATP-aryl azide and ATP-benzophenone, offered the most robust crosslinking, whereas electrophilic ATP-aryl fluorosulfate promoted the most effective proximity-enabled crosslinking. The data will guide future applications of kinase-catalyzed crosslinking to study normal and disease biology.

Implant Texture and Capsular Contracture: A Review of Cellular and Molecular Pathways.

Background: Capsular contracture (CC) is a leading cause of morbidity in implant-based breast surgery. Implant surface texture has been implicated in CC development, yet its etiopathogenesis remains unclear. We conducted a systematic review to determine the influence of implant surface texture on cellular and molecular mechanisms involved in the etiopathogenesis of CC. Methods: A systematic review of the MEDLINE, Embase, Web of Science, and Scopus databases was completed to examine the influence of implant texture on cellular and molecular pathways leading to CC. Excluded articles were reviews and those examining solely the clinical presentation of CC. Results: Development of CC includes prolonged inflammation, increased myofibroblast density, parallel arrangement of collagen fibers, and biofilm formation. When compared with textured implants, smooth implants are associated with reduction in parallel collagen, capsule thickness, and sheer frictional force. Microtextured implants trigger a reduced macrophage response and decreased fibroblast activation as compared with smooth and macrotextured surfaces. Bacterial counts on microtextured and smooth surfaces are significantly lower than that of macrotextured surfaces. Both micro- and macrotextured implants have increased matrix metalloproteinases and activation of tumor necrosis factor α pathway, with increased activation of the transforming growth factor ß1 pathway relative to smooth implants. Conclusions: Implant surface texture alters the cellular and molecular mechanisms in the chronic inflammatory process leading to CC. Given the complex biological system of cellular and molecular events in CC, a mathematical model integrating these influences may be optimal to deduce the etiopathogenesis.

Extended-Spectrum Beta-Lactamase Shigella sonnei Cluster Among Men Who Have Sex with Men in Chicago, Illinois-July-October 2022.

Drug-resistant shigellosis is increasing, particularly among men who have sex with men (MSM). During July-October 2022, an extended-spectrum beta-lactamase producing Shigella sonnei cluster of 9 patients was identified in Chicago, of whom 8 were MSM and 6 were festival attendees. The cluster also included 4 domestic travelers to Chicago. Sexual health care for MSM should include shigellosis diagnosis and prevention.

Injury risk factors related to sport specialization in high school basketball: a prospective study.

CONTEXT: Research that has examined the association between specialization and injury in basketball has been limited to cross-sectional or retrospective studies. OBJECTIVE: To determine whether specialization is a risk factor for injury among high school basketball athletes. DESIGN: Prospective cohort study. SETTING: Basketball players from 12 high schools participating in the National Athletic Treatment, Injury, and Outcomes Network Surveillance Program (NATION-SP) were recruited prior to the 2022-2023 interscholastic basketball season. PATIENTS OR OTHER PARTICIPANTS: 130 athletes (mean age (SD) = 15.6 (1.3); girls' basketball: n=68 (52.3%)). MAIN OUTCOME MEASURES: Participants completed a questionnaire prior to the start of their school basketball season that had questions regarding participation in various specialized sport behaviors. During the basketball season, the school's athletic trainer reported all athletic exposures (AEs) and injuries (regardless of time loss) for participating athletes into NATION-SP. Injury incidence (IR) and incidence rate ratios (IRR) with 95% confidence intervals [95%CI] were calculated for the specialized sport behaviors previously described. RESULTS: There was no difference in injury risk between highly specialized and low specialized athletes (IRR [95%CI]: 1.9 [0.9, 3.7]). Players who participated in basketball year-round were twice as likely to sustain an injury compared to those who did not play year-round (IRR [95%CI]: 2.1 [1.1, 3.6]). Similarly, players who reported participating in basketball skills camps were at increased risk of injury compared to athletes who did not participate in basketball skill camps (IRR [95%CI]: 2.5 [1.2, 5.7]). CONCLUSION: Injury risk related to sport specialization in basketball may be specific to certain behaviors such as year-round play and participation in skills camps. Validated measures of comprehensive sport activity are needed to better measure specialization in youth sports to better determine injury risk related to sport specialization and develop injury prevention programs for basketball athletes.

Urothelium-Derived Prostanoids Enhance Contractility of Urinary Bladder Smooth Muscle and Stimulate Bladder Afferent Nerve Activity in the Mouse.

The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins and other prostanoids, that can modulate bladder function. We investigated whether select substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 mM) or the voltage-dependent Ca2+ channel blocker diltiazem (50 mM), whereas blocking neuronal sodium channels with tetrodotoxin (1 mM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca2+ channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling.

A high-throughput lysosome trafficking assay guides ligand selection and elucidates differences in CD22-targeted nanodelivery.

Targeted nanoparticles offer potential to selectively deliver therapeutics to cells; however, their subcellular fate following endocytosis must be understood to properly design mechanisms of drug release. Here we describe a nanoparticle platform and associated cell-based assay to observe lysosome trafficking of targeted nanoparticles in live cells. The nanoparticle platform utilizes two fluorescent dyes loaded onto PEG-poly(glutamic acid) and PEG-poly(Lysine) block co-polymers that also comprise azide reactive handles on PEG termini to attach antibody-based targeting ligands. Fluorophores were selected to be pH-sensitive (pHrodo Red) or pH-insensitive (Alexafluor 488) to report when nanoparticles enter low pH lysosomes. Dye-labelled block co-polymers were further assembled into polyion complex micelle nanoparticles and crosslinked through amide bond formation to form stable nano-scaffolds for ligand attachment. Cell binding and lysosome trafficking was determined in live cells by fluorescence imaging in 96-well plates and quantification of red- and green-fluorescence signals over time. The platform and assay was validated for selection of optimal antibody-derived targeting ligands directed towards CD22 for nanoparticle delivery. Kinetic analysis of uptake and lysosome trafficking indicated differences between ligand types and the ligand with the highest lysosome trafficking efficiency translated into effective DNA delivery with nanoparticles bearing the optimal ligand.

The ability of this pH-sensitive reporter platform to rapidly screen ligands in nanoparticle format will enable identification and production of targeted NPs with desired lysosome trafficking properties.

Genetic Foundation of Prostaglandin Metabolism Influences Patent Ductus Arteriosus Closure in Extremely Low Birth Weight Infants.

OBJECTIVE: Prostaglandins (PGs) play a major role in maintaining patency of the ductal arteriosus (DA). Pulmonary 15-hydroxyprostaglandin dehydrogenase (PGDH), which is ecoded by the hydroxyprostaglandin dehydrogenase (HPGD) gene, is the primary enzyme responsible for PG breakdown. Animal studies have shown HPGD-knockout mice have significantly higher prostaglandin E2 levels and no ductal remodeling. Functional variants of the HPGD gene that alter PG breakdown have not been studied in preterm infants with patent ductus arteriosus (PDA). STUDY DESIGN: This was an observational cohort study including extreme low birth weight (ELBW) infants classified as having spontaneous, medical, or procedural (transcatheter or surgical ligation) closure of their DA. Urine prostaglandin E metabolite (PGEM) levels were measured in ELBW infants following ibuprofen treatment using competitive ELISA. HPGD genetic variants rs8752, rs2612656, and rs9312555 were analyzed. Kruskal-Wallis, Fisher's exact, chi square, logistic regression, and Wilcoxon signed-rank tests were used; p < 0.05 was considered significant. RESULTS: Infants in the procedural closure group had a younger gestational age (GA). The incidence of spontaneous closure or medical closure was higher compared to procedural closure in the presence of any minor allele of rs8752 (67 and 27%, respectively; p = 0.01), when adjusted for GA and gender. Haplotype analysis of three variants of HPGD revealed differences when comparing the spontaneous and medical closure group to the procedural group (p < 0.05). Urinary PGEM levels dropped significantly in those ELBW infants who responded to ibuprofen (p = 0.003) in contrast to those who did not respond (p = 0.5). CONCLUSION: There was a different genotype distribution for the rs8752 genetic variant of the HPGD gene-as it relates to the mode of treatment for ELBW infants with PDA. We speculate that medical management in the presence of this variant facilitated additional PG breakdown, significantly abrogating the need for procedural closure. Additionally, differences in genotype and haplotype distributions implicate a specific HPGD genetic foundation for DA closure in ELBW infants. KEY POINTS: · PGs and their metabolism play a major role in PDA patency or closure.. · Genetic variants of the HPGD gene influence mode of treatment of PDA in ELBW infants.. · ELBW infants with PDA that responded to medical closure had significantly decreased urine PGEM levels..

Rate and Location of Reulceration and Reamputation After Partial First-Ray Amputation versus Hallux Amputation in Diabetic and Nondiabetic Populations.

BACKGROUND: We sought to determine the rates of reulceration and reamputation in individuals who underwent partial first-ray amputations versus hallux amputations in diabetic and nondiabetic populations. METHODS: Eighty-four amputations were reviewed in a retrospective fashion. A retrospective medical record review was performed to determine patients who underwent a hallux amputation, both partial and complete, and patients who underwent a partial first-ray amputation. Only patients from 2007 to 2019 were reviewed. The reulceration rate of hallux amputations was 61% compared with a partial first-ray amputation reulceration rate of 74%. RESULTS: The reamputation rate of hallux amputation versus partial first-ray amputation was 43% versus 51%. At final follow-up, it was statistically significant that patients who underwent hallux amputation were more likely to be healed than those who underwent partial first-ray amputation, regardless of reulceration or reamputation. In addition, patients who underwent hallux amputation went on to digital amputation, and those who underwent partial first-ray amputation went on to transmetatarsal amputation. CONCLUSIONS: Comparing partial first-ray amputation to hallux amputation, hallux amputation patients are more prone to subsequent digital ulceration. Patients who initially undergo hallux amputation have variable subsequent amputations, often digital. Reulceration primarily occurs at the incision site for partial first-ray amputations, with a higher likelihood of subsequent transmetatarsal amputation. Patients with a medical history of diabetes and staged procedures are more likely to receive partial first-ray amputations. However, hallux amputation patients have a lower risk of reulceration and reamputation, regardless of subsequent events. These findings underscore the importance of discussing risks and preventive measures with patients undergoing such amputations, emphasizing postoperative examinations for specific areas of concern. Hallux amputation appears to offer greater protection against reulceration and reamputation for both diabetic and nondiabetic populations.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/µL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/µL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/µL, P=0.01) and larger target tumor volume (median 125 vs. 62 cm3, P=0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death (P=0.04); 1-year OS rates were 63% vs 77% (P=0.03). Receipt of photon versus proton-based RT (OR=3.50, P=0.02), higher mean liver dose (OR=1.19, P<0.01), and longer RT duration (OR=1.49, P=0.02) predicted severe lymphopenia. CONCLUSIONS: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Anterior pituitary gland volume mediates associations between pubertal hormones and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g., internalizing symptoms) during adolescence. Surprisingly, studies have not yet examined associations among these factors and increasing transdiagnostic symptomology, despite DHEA being a primary output of the anterior PG. Therefore, the current study sought to fill this gap by examining whether anterior PG volume specifically mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample ( N = 114, 9 - 17 years, M age = 12.87, SD = 1.88). Following manual tracing of the anterior and posterior PG, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. These results suggest specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for psychopathology during adolescence. This work not only highlights the importance of separately tracing the anterior and posterior PG, but also suggests that transdiagnostic factors like dysregulation are useful in parsing hormone-related increases in mental health symptoms in youth.