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Objective: This study aimed to determine health care disparities in evaluation and admission among underserved racial and ethnic minority groups presenting with cardiovascular complaints during the first postpartum year according to patient and provider demographics., Study Design: A retrospective cohort study was performed on all postpartum patients who sought emergency care between February 2012 and October 2020 in a large urban care center in Southeastern Texas. Patient information was collected according to International Classification of Diseases 10th Revision codes and individual chart analysis. Race, ethnicity, and gender information were self-reported for both patients on hospital enrollment forms and emergency department (ED) providers on their employment records. Statistical analysis was performed with logistic regression and Pearson's chi-square test., Results: Of 47,976 patients who delivered during the study period, 41,237 (85.9%) were black, Hispanic, or Latina and 490 (1.1%) presented to the ED with cardiovascular complaints. Baseline characteristics were similar between groups; however, Hispanic or Latina patients were more likely to have had gestational diabetes mellitus during the index pregnancy (6.2 vs. 18.3%). There was no difference in hospital admission between groups (17.9% black vs. 16.2% Latina or Hispanic patients). There was no difference in the hospital admission rate by provider race or ethnicity overall ( p  = 0.82). There was no difference in the hospital admission rate when a patient was evaluated by a provider of a different race or ethnicity (relative risk [RR] = 1.08, CI: 0.6-1.97). There was no difference in the rate of admission according to the self-reported gender of the provider (RR = 0.97, CI: 0.66-1.44)., Conclusion: This study illustrates that disparities did not exist in the management of racial and ethnic minority groups who presented to the ED with cardiovascular complaints during the first postpartum year. Patient-provider discordance in race or gender was not a significant source of bias or discrimination during the evaluation and treatment of these patients., Key Points: · Adverse postpartum outcomes disproportionately affect minorities.. · There was no difference in admissions between minority groups.. · There was no difference in admissions by provider race and ethnicity.., Competing Interests: None declared., (Thieme. All rights reserved.)

Plasmodium parasites, the eukaryotic pathogens that cause malaria, feature three distinct invasive forms tailored to the host environment they must navigate and invade for life cycle progression. One conserved feature of these invasive forms is the micronemes, apically oriented secretory organelles involved in egress, motility, adhesion, and invasion. Here we investigate the role of GPI-anchored micronemal antigen (GAMA), which shows a micronemal localization in all zoite forms of the rodent-infecting species Plasmodium berghei. ∆GAMA parasites are severely defective for invasion of the mosquito midgut. Once formed, oocysts develop normally, however, sporozoites are unable to egress and exhibit defective motility. Epitope-tagging of GAMA revealed tight temporal expression late during sporogony and showed that GAMA is shed during sporozoite gliding motility in a similar manner to circumsporozoite protein. Complementation of P. berghei knockout parasites with full-length P. falciparum GAMA partially restored infectivity to mosquitoes, indicating conservation of function across Plasmodium species. A suite of parasites with GAMA expressed under the promoters of CTRP, CAP380, and TRAP, further confirmed the involvement of GAMA in midgut infection, motility, and vertebrate infection. These data show GAMA's involvement in sporozoite motility, egress, and invasion, implicating GAMA as a regulator of microneme function., (© 2023 John Wiley & Sons Ltd.)

Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with limited relevance for understanding the molecular relationship between diseases or for identifying disease-specific markers. In this study, we used a normalization approach to compare gene expression across nine inflammatory skin diseases. The normalized datasets were found to retain differential expression signals that allowed unsupervised disease clustering and identification of disease-specific gene signatures. Using the NS-Forest algorithm, we identified a minimal set of biomarkers and validated their use as diagnostic disease classifier. Among them, PTEN was identified as being a specific marker for cutaneous lupus erythematosus and found to be strongly expressed by lesional keratinocytes in association with pathogenic type I IFNs. In fact, PTEN facilitated the expression of IFN-β and IFN-κ in keratinocytes by promoting activation and nuclear translocation of IRF3. Thus, cross-comparison of tissue transcriptomics is a valid strategy to establish a molecular disease classification and to identify pathogenic disease biomarkers., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Plasmodium sporozoites invade hepatocytes and transform into liver stages within a parasitophorous vacuole (PV). The parasites then grow and replicate their genome to form exoerythrocytic merozoites that infect red blood cells. We report that the human malaria parasite Plasmodium falciparum (Pf) expresses a C-type ATP-binding cassette transporter, Pf ABCC2, which marks the transition from invasive sporozoite to intrahepatocytic early liver stage. Using a humanized mouse infection model, we show that Pf ABCC2 localizes to the parasite plasma membrane in early and mid-liver stage parasites but is not detectable in late liver stages. Pf abcc2 - sporozoites invade hepatocytes, form a PV, and transform into liver stage trophozoites but cannot transition to exoerythrocytic schizogony and fail to transition to blood stage infection. Thus, Pf ABCC2 is an expression marker for early phases of parasite liver infection and plays an essential role in the successful initiation of liver stage replication., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Background: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD)., Objective: Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD., Methods: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate-to-severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP-NRS), Investigator's Global Assessment (IGA), changes in sleep and responders with ≥ 4-point improvement on PP-NRS., Results: There was a significantly greater itch relief apparent by Day 2 (-22.8% vs -12.3% PP-NRS; P = 0.005) which continued to improve through week 16 (-68.5% vs -30.9% PP-NRS; P < 0.001). At week 16, PP-NRS ≥ 4-point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P ≤ 0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by Day 3 (-26.6% vs -9.0%; P < 0.001) which further improved till week 16 (-76.0% vs -36.5%; P < 0.001). Also for the EASI score a separation between groups in favour of nemolizumab was observed by week 1 (P ≤ 0.001), which increased through week 16 (-68.6% vs. -42.6%; P = 0.002). Finally, the degree of response was greater in nemolizumab-treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P < 0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P = 0.002). Nemolizumab was safe and well-tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events., Conclusions: Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥ 16 at baseline., (© 2021 Galderma SA. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose: Benign prostatic hyperplasia is one of the most common conditions seen by a general urologist. Validated questionnaires provide insight into patient symptoms, however office based uroflow devices are limited by the variability of voiding behavior. Using a home uroflow device, we assessed individual voiding variability, temporal distribution of voiding parameters and the impact of age on voiding., Materials and Methods: Between April 2019 and June 2020, 19,824 unique voiding profiles were captured using the Stream Dx Uroflowmeter and retrospectively analyzed. Age and number of voids were summarized by mean±standard deviation. We used mixed effects models to compare average values and intrapatient variability of voiding parameters to time of day and age. The coefficient of variation was used to assess intrapatient variability., Results: A total of 637 patients were identified with 625 meeting inclusion criteria, producing 19,824 voids. Mean age was 67 (±10.2) years old, and each patient provided on average 5 (±3.3) voids a day through 7 days. Average intrapatient voiding parameters showed notable variability, where the coefficient of variation for maximum flow was 27.6% (95% CI 26.6-28.6). Early morning voids were associated with higher volume and lower number of voids. As age progressed, voiding profiles worsened in a linear fashion. Afternoon and evening voids were associated with reduced intrapatient variability relative to early morning voids., Conclusions: Assessment of 19,824 uroflows using an accurate and precise home uroflow device demonstrates that an individual's voiding parameters vary greatly from day to day, throughout the day, and worsen with age. Multiple measurements performed at home provides a more realistic assessment of true voiding behavior by capturing individual voiding variability and can help urologists make better decisions in patient care.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset ( n = 1,032), with performance assessed in a separate test dataset ( n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease., Competing Interests: The authors declare no competing interest.

Objective: Research suggests that higher childhood self-regulation (CSR) predicts lower adiposity in adolescence. However, it is unclear whether this relationship differs by sex or by baseline weight status. Thus, this study investigated these questions in a longitudinal, community-based cohort., Methods: The cohort included 221 girls and 214 boys. At age 9, CSR was assessed via parent/teacher reports of effortful control, and childhood BMI z scores (BMIz) were calculated from staff measurements. Late-adolescent waist-to-height ratio was based on staff measurements at age 18., Results: CSR has a small inverse correlation with concurrent childhood BMIz in girls, but not in boys. Prospectively, however, CSR has a small inverse association with late-adolescent weight-to-height ratio in both sexes, after adjusting for childhood BMIz and other childhood predictors. This prospective association is marginally stronger for girls with higher (vs. lower) childhood BMIz., Conclusions: CSR inversely predicts changes in adiposity across adolescence in both sexes, with some evidence that this association is stronger for girls with higher (vs. lower) childhood adiposity. However, this inverse association between CSR and adiposity may emerge earlier in girls. Future research should examine the causal status of CSR and its relationship to behaviors (e.g., diet)., (© 2020 The Obesity Society.)

Objectives: To evaluate various Prostate-Specific Antigen (PSA) thresholds at which a 18 F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment., Methods: We analyzed available records of men who underwent a 18 F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized., Results: A total of 115 men underwent imaging with 18 F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38., Conclusion: This study constitutes an early single institution series evaluating the use of 18 F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Turner syndrome is a chromosomal disorder that occurs in an estimated 1 in 2500 female live births. It is estimated that 6%-12% of all Turner syndrome patients will be a mosaic with Y-chromosomal elements putting them at risk for gonadoblastoma and subsequent dysgerminoma. While 30%-50% of this population demonstrate gonadoblastoma, we only found 23 reported cases of dysgerminoma in the literature, and no reported cases of seminoma. We present the first case of seminoma in a phenotypic Turner 15-year-old female after prophylactic gonadectomy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Given the pervasive nature of child abuse and neglect, multilevel public health approaches are necessary. Implementation science can help in understanding the most effective ways to build infrastructure and support delivery of such approaches. In this theoretical paper, we describe the implementation of the Positive Parenting Program (Triple P), an evidence-based population-level parenting program in South Carolina. While implementation science has informed how to move population-level efforts to scale, we discuss challenges that persist in practice, such as when there is a need for multiple stakeholders to understand, support, and apply implementation best practices in a systematic and consistent way. To address this challenge, we introduce the role of a Community Capacity Coach, who lives in the local community and works towards the implementation of Triple P. The Coach is responsible for bridging gaps between the local community and statewide support systems. We detail the ways in which the Coach's role aligns with key intermediary functions, and how the Coach is embedded within the larger Triple P statewide support system. We then discuss the assessment of the Coach's impact; and conclude with future directions and next steps for this role within Triple P South Carolina., (© 2020 Wiley Periodicals LLC.)

The bilaterally symmetrical, feeding larval stage is an ancestral condition in echinoderms. However, many echinoderms have evolved abbreviated development and form a pentamerous juvenile without a feeding larva. Abbreviated development with a non-feeding vitellaria larva is found in five families of brittle stars, but very little is known about this type of development. In this study, the external anatomy, ciliary bands, neurons, and muscles were examined in the development of the brooded vitellaria larva of Ophioplocus esmarki. The external morphology throughout development shows typical vitellaria features, including morphogenetic movements to set up the vitellaria body plan, an anterior preoral lobe, a posterior lobe, transverse ciliary bands, and development of juvenile structures on the mid-ventral side. An early population of neurons forms at the base of the preoral lobe at the pre-vitellaria stage after the initial formation of the coelomic cavities. These early neurons may be homologous to the apical neurons that develop in echinoderms with feeding larval forms. Neurons form close to the ciliary bands, but the vitellaria larva lacks the tracts of neurons associated with the ciliary bands found in echinoderms with feeding larvae. Additional neurons form in association with the axial complex and persist into the juvenile stage. Juvenile nerves and muscles form with pentamerous symmetry in the late vitellaria stage in a manner similar to their development within the late ophiopluteus larva. Even though O. esmarki is a brooding brittle star, its developmental sequence retains the general vitellaria shape and structure; however, the vitellaria larvae are unable to swim in the water column.

Importance: Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression., Objective: To assess safety and objective response rate of durvalumab combined with tremelimumab., Design, Setting, and Participants: The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1-low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific., Interventions: Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy., Main Outcomes and Measures: Safety and tolerability and efficacy measured by objective response rate., Results: Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively., Conclusions and Relevance: In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way., Trial Registration: clinicaltrials.gov Identifier: NCT02319044.

Background: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC., Patients and Methods: Immunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS)., Results: Among evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9-24.4); 29.4% (95% CI, 15.1-47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5-21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9-3.7) and 7.1 months (95% CI, 4.9-9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5-22.1) and 33.6% (95% CI, 24.8-42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up., Conclusion: Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

An animal's ability to navigate an olfactory environment is critically dependent on the activities of its first-order olfactory receptor neurons (ORNs). While considerable research has focused on ORN responses to odorants, the mechanisms by which olfactory information is encoded in the activities of ORNs and translated into navigational behavior remain poorly understood. We sought to determine the contributions of most Drosophila melanogaster larval ORNs to navigational behavior. Using odorants to activate ORNs and a larval tracking assay to measure the corresponding behavioral response, we observed that larval ORN activators cluster into four groups based on the behavior responses elicited from larvae. This is significant because it provides new insights into the functional relationship between ORN activity and behavioral response. Subsequent optogenetic analyses of a subset of ORNs revealed previously undescribed properties of larval ORNs. Furthermore, our results indicated that different temporal patterns of ORN activation elicit different behavioral outputs: some ORNs respond to stimulus increments while others respond to stimulus decrements. These results suggest that the ability of ORNs to encode temporal patterns of stimulation increases the coding capacity of the olfactory circuit. Moreover, the ability of ORNs to sense stimulus increments and decrements facilitates instantaneous evaluations of concentration changes in the environment. Together, these ORN properties enable larvae to efficiently navigate a complex olfactory environment. Ultimately, knowledge of how ORN activity patterns and their weighted contributions influence odor coding may eventually reveal how peripheral information is organized and transmitted to subsequent layers of a neural circuit.

The link between youth homelessness and mental health functioning was examined using state population-representative 2015 Youth Risk Behavior Survey (YRBS) data. The moderating role of victimization and perceived teacher support also was examined. Consistent with hypotheses, results indicated that homelessness was associated with greater mental health challenges, more victimization, and less teacher support. The association between homelessness and mental health was not moderated by perceived teacher support. However, victimization experiences served as a moderator such that more victimization exacerbated the effect of homelessness on mental health challenges. This study supports the utility of the YRBS for gaining understanding of the experiences and needs of youth experiencing homelessness and adds to the growing literature on predictors of individual differences in mental health functioning of these vulnerable youth.

Background: To describe the impact of supra-physiologic anabolic-androgenic steroid (AAS) use, including agent, dosage, and duration of therapy, on sexual function., Methods: We reviewed data from an online survey of AAS users to evaluate their sexual function on and off AAS. The online survey consisted of questions addressing demographics, anabolic steroid use and patterns, ancillary medications, testosterone (T)-related symptoms while on and off of therapy, as well as sexual function which was assessed using the 5-item, International Index of Erectile Function (IIEF-5)., Results: A total of 321 men responded to the survey, of which 90 failed to meet inclusion criteria, for a final cohort of 231 AAS users. The majority of men were Caucasian (85%), employed (62%), and younger than 35 years (58%), while an equal mix were single (47%) or married (46%). The mean IIEF-5 was 22.5, with higher scores associated with increased T dosages (>600 mg/week), use of 17-alpha alkylated hormones and anti-estrogens, and absence of concurrent medical conditions. Lower mean IIEF scores were associated with current and pre-AAS low T symptoms, self-reported angry or violent tendencies, self-reported erectile dysfunction (ED), decreased libido, decreased energy, and depression. After controlling for age, low T symptoms and decreased energy remained significantly associated with lower IIEF scores. Among 127 men reporting de novo decreased libido when not taking AAS, several factors were significantly associated including frequency and duration of T and use of adjunctive therapies, while post-cycle therapies were protective. Men who reported any other de novo symptom (decreased energy, libido, muscle mass or depression) after discontinuing T were also more likely to report de novo ED, as well as those using >10 years or for >40 weeks per year., Conclusions: The long-term impact of high dose AAS use on sexual function remains poorly defined. Although high T dosages appeared to be protective of erectile function during use, de novo symptoms such as decreased libido and ED occurred more frequently after discontinuing T, particularly among those using more frequently and for longer durations. Given the importance of these findings, long-term studies evaluating the impacts of discontinuing T on sexual dysfunction are indicated., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose of Review: Male factor infertility is a complex and multifaceted problem facing the modern urologist and is identified in 30-40% of infertile couples. This review focuses on the use of ultrasound, as an adjunct screening tool, in the initial evaluation of male infertility., Recent Findings: Access to male reproductive urologist for assessment of male infertility is limited and about a quarter of infertile couples do not complete the male component in their infertility assessment. Ultrasound evaluation of the infertile male is low-cost and non-invasive and helps uncover underlying pathologies that may be missed during the initial assessment. The addition of ultrasound allows the physician to accurately assess testicular anatomy and dimensions, as well as vascular environments, which may help guide treatment decisions. Scrotal ultrasound evaluation, in conjunction with a semen analysis and as an adjunct to physical exam, can be offered in the initial assessment of men who present for infertility consultation given its low cost, non-invasive nature, and ability to detect and discriminate between various etiologies of male infertility. Further, when directed by physical exam and semen analysis findings, it provides a valuable tool to select men for referral to a reproductive urologist, especially for infertile couples who are only screened by reproductive endocrinologists and female infertility specialists.

Rumination, a perseverative cognitive process that involves repetitively and passively focusing on negative emotions, is a transdiagnostic risk factor for the development of psychopathology. Although rumination has been linked to various forms of psychopathology including depression, anxiety, and alcohol misuse, little is known about the conditions that lead to multifinality. Here, we test putative moderators (Nolen-Hoeksema & Watkins, 2011) of the association between rumination and subsequent internalizing symptoms and frequency of alcohol use during adolescence. Participants included 388 youth (52% girls; 90% Caucasian) in a longitudinal birth cohort study who completed questionnaires in Grades 9 and 11. Brooding, a maladaptive form of rumination measured in Grade 9, was associated with greater internalizing symptoms in Grade 11 and greater perceived peer rejection in Grade 9 amplified this association. Brooding was also associated with greater frequency of alcohol use among adolescents who reported having more friends who use alcohol. Gender differences were also examined. Findings provide support for some of the predictions regarding moderators of multifinality made by Nolen-Hoeksema and Watkins. Implications of understanding divergent trajectories in the prevention of psychopathology are discussed.

Background: Barriers hinder medical students from reporting breaches in professional behaviour, which can adversely impact institutional culture. No studies have reported student perspectives on how to address these barriers successfully. Our study (i) evaluated the likelihood of reporting based on violation severity, (ii) assessed barriers to reporting and (iii) elicited students' proposed solutions., Methods: Four medical students designed a cross-sectional study in 2015. In response to seven scenarios, students rated the likelihood of reporting the violation, indicated perceived barriers and identified solutions. Additional questions investigated the perceived importance of professionalism, confidence in understanding professionalism and trust in administrative protection from negative consequences., Results: Two hundred and seventy-two students in their clinical years (MS2-4) responded to the survey (RR = 50%). Students were 70-90% likely to report major violations, but < 30% likely to report minor or moderate violations. Barriers included concerns about an uncomfortable relationship (41%), potential negative repercussions on grades or opportunities (23%), and addressing by direct discussion rather than reporting (23%). Solutions included simplified reporting, control over report release date, improved feedback to reporters, training for real-time resolution of concerns and a neutral resource to help students triage concerns. No differences existed between classes regarding the importance or understanding of professionalism. In linear regression, only importance of professionalism predicted likelihood of reporting and this did not change with training., Conclusions: Hindered by common barriers, students are unlikely to report a violation unless it is a serious breach of professionalism. Student-derived solutions should be explored by medical school administrators to encourage reporting of violation of professionalism., (© 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Considering the association between children's quality of relationships with teachers and their academic adjustment, information pertaining to how abused children are functioning in their relationships with teachers could be useful in promoting their academic success- yet there has been limited research in this area. The purpose of this study was to use cluster analyses to explore within-group differences in relational schemas and quality of student-teacher relationships for 70 abused children. Two clusters of abused children emerged, and as hypothesized, there were significant differences in student-teacher relationships for the two clusters. The cluster with more positive relational schemas had less conflict and less dependency reported by their teachers compared to the cluster with negative relational schemas. However, there were no differences between the clusters in terms of closeness with teachers. Implications for practice in schools is discussed.

Unlabelled: September 11, 2001 saw the dawn of the US-led global war on terror, a combined diplomatic, military, social, and cultural war on terrorist activities. Chemical, biological, radiological, nuclear, and high-yield explosives (CBRNE), as a group of tactics, are often the preferred weapons of terrorists across the globe. We undertook a survey of US medical schools to determine what their self-reported level of training for terrorist events encompasses during the four years of undergraduate medical education., Methods: We surveyed 170 medical schools in the US and Puerto Rico using a five-question, internet-based survey, followed by telephone calls to curriculum offices for initial nonresponders. We used simple descriptive statistics to analyze the data., Results: A majority of US medical schools that completed the survey (79 schools or 65.3%) have no required lecture or course on CBRNE or terrorist activities during the first or second year (preclinical years). Ninety-eight out of the 121 respondents (81.0%), however, believed that CBRNE training was either very important or somewhat important, as reflected in survey answers., Conclusions: Most physician educators believe that training in CBRNE is important; however this belief has not resulted in widespread acceptance of a CBRNE curriculum in US medical schools.

Fraley's syndrome results from a rare anatomic variant of the renal vasculature leading to compression of the upper pole infundibulum, caliectasis, hematuria, and flank pain. To date there have been few reported cases in which this condition was treated using a minimally invasive approach. Here, we report a case in which a patient with Fraley's syndrome was successfully treated by performing a laparoscopic YV-infundibulo-pyeloplasty with vasculopexy of a posterior segmental renal artery. Minimally invasive collecting system reconstruction without vascular clamping is feasible, potentially less destructive and offers significant advantages in terms of intraoperative visualization and perioperative patient morbidity.

Drawing on conceptual models illustrating the advantages of a multisystemic, interactive, developmental approach to understanding development, the present study examines the covariation of stress and sex hormones across the adolescent transition and the effect of early life stress (ELS) on neuroendocrine coupling to gain insight into atypical development. Morning levels of cortisol, testosterone, and dehydroepiandrosterone (DHEA) were assessed at ages 11, 13, and 15; ELS was assessed during the infancy and preschool periods. Hierarchical linear modeling revealed that cortisol-DHEA coupling patterns progressed to tight, positive coupling across adolescence. Cortisol-testosterone coupling was positive at age 11 but became more negative at ages 13 and 15. Exposure to ELS resulted in more adultlike neuroendocrine coupling patterns earlier in life than non-exposed youth; however the effect of ELS on cortisol-testosterone coupling was unique to girls. Results illustrate trajectories of neuroendocrine coupling that may be unique to adolescence. Moderation by ELS suggests that early stress exposure may prompt earlier adultlike neuroendocrine coupling, particularly within girls, which may contribute to early pubertal development., (© 2013 Wiley Periodicals, Inc.)

A large body of research has linked hypothalamic-pituitary-adrenal (HPA) axis function and alcohol consumption, including work suggesting that flatter diurnal cortisol slopes are associated with greater alcohol use. A lack of longitudinal studies and a focus on adult and alcoholic populations leaves unclear whether such associations are also present in younger, non-clinical populations and whether flatter diurnal slopes are a consequence of or preexisting risk factor for alcohol use; however, theory suggests such associations may be mutually reinforcing. In a longitudinal, community sample of 200 (55% female) adolescents, the current study demonstrates that flatter diurnal cortisol slope at age 11 predicts higher levels of alcohol use from ages 15-18, and that heavier alcohol use in turn predicts further flattening of diurnal cortisol rhythm at age 18.5. This is the first study to demonstrate a longitudinal chain of associations between diurnal cortisol slope and alcohol use. Findings support contemporary theoretical models of the neurobiological processes underlying alcohol use and can inform future research on risk factors for and consequences of underage drinking., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for increased probability of reproducing before dying via a process of accelerated reproductive maturation. Using data from 73 females, we test the following propositions using path analysis: (a) greater exposure to prenatal stress predicts greater maternal depression and negative parenting in infancy, (b) which predicts elevated basal cortisol at 4.5 years, (c) which predicts accelerated adrenarcheal development, (d) which predicts more physical and mental health problems at age 18. Results prove generally consistent with these propositions, including a direct link from cortisol to mental health problems. DOoHaD investigators should consider including early sexual maturation as a core component linking early adversity and stress physiology with poor health later in life in females., ((c) 2015 APA, all rights reserved).)

An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism) including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG) has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction.

Although adolescence is marked by increased negative life events and internalizing problems, few studies investigate this association as an ongoing longitudinal process. Moreover, while there are considerable individual differences in the degree to which these phenomena are linked, little is known about the origins of these differences. The present study examines early life stress (ELS) exposure and early-adolescent longitudinal afternoon cortisol level as predictors of the covariation between internalizing symptoms and negative life events across high school. ELS was assessed by maternal report during infancy, and the measure of cortisol was derived from assessments at ages 11, 13, and 15 years. Life events and internalizing symptoms were assessed at ages 15, 17, and 18 years. A two-level hierarchical linear model revealed that ELS and cortisol were independent predictors of the covariation of internalizing symptoms and negative life events. Compared to those with lower levels of ELS, ELS-exposed adolescents displayed tighter covariation between internalizing symptoms and negative life events. Adolescents with lower longitudinal afternoon cortisol displayed tighter covariation between negative life events and internalizing symptoms, while those with higher cortisol demonstrated weaker covariation, partially due to increased levels of internalizing symptoms when faced with fewer negative life events.

Despite widespread recognition that the physiological systems underlying stress reactivity are well coordinated at a neurobiological level, surprisingly little empirical attention has been given to delineating precisely how the systems actually interact with one another when confronted with stress. We examined cross-system response proclivities in anticipation of and following standardized laboratory challenges in 664 4- to 14-year-olds from four independent studies. In each study, measures of stress reactivity within both the locus coeruleus-norepinephrine system (i.e., the sympathetic and parasympathetic branches of the autonomic nervous system) and the corticotrophin releasing hormone system (i.e., the hypothalamic-pituitary-adrenal axis) were collected. Latent profile analyses revealed six distinctive patterns that recurred across the samples: moderate reactivity (average cross-system activation; 52%-80% of children across samples), parasympathetic-specific reactivity (2%-36%), anticipatory arousal (4%-9%), multisystem reactivity (7%-14%), hypothalamic-pituitary-adrenal axis specific reactivity (6%-7%), and underarousal (0%-2%). Groups meaningfully differed in socioeconomic status, family adversity, and age. Results highlight the sample-level reliability of children's neuroendocrine responses to stress and suggest important cross-system regularities that are linked to development and prior experiences and may have implications for subsequent physical and mental morbidity.

Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Study Objectives: To examine the patterns of insomnia and sleep-related movement from ages 4.5 to 9 years, their concurrent associations with mental health symptoms in childhood, and the longitudinal associations of sleep-problem persistence with mental health symptoms at ages 9 and 18 years., Design: A 14-year prospective follow-up study. Assessments included maternal report on the Children's Sleep Habits Questionnaire at ages 4.5 and 9, and child mental health symptoms via maternal report at age 4.5, multi-informant (child, teacher, mother) report at age 9, and adolescent report at age 18., Setting: Community., Participants: A total of 396 children (51% female)., Interventions: N/A., Measurements and Results: Sleep problems were more common at age 4.5 than 9; symptoms of insomnia and abnormal sleep movement both had persistence rates of 9-10%. At age 4.5, insomnia was associated with hostile-aggressive and hyperactive-distractible behavior, but there were no significant associations for sleep movement. At age 9, both insomnia and sleep movement were associated with symptoms of depression, externalizing, and attention deficit hyperactivity disorder (ADHD). Insomnia persistence was associated with symptoms of depression, externalizing, and ADHD at age 9 and anxiety and externalizing at age 18; sleep- movement persistence was associated with externalizing and ADHD at age 9, and ADHD at age 18. The age 18 persistence effects for insomnia and anxiety and for sleep movement and ADHD were significant when controlling for earlier mental health., Conclusions: Childhood insomnia and sleep movement are common and associated with mental health symptoms. Their persistence from middle to late childhood predicts associations with specific types of mental health symptoms at age 18.

Objective: Past research has associated childhood characteristics and experiences with alcohol use at single time points in adolescence. Other work has focused on drinking trajectories across adolescence but with risk factors typically no earlier than middle or high school. Similarly, although the connection between underage drinking and affiliation with deviant friends is well established, early risk factors for their covariation across adolescence are uncertain. The present study examines the influence of early individual and contextual factors on (a) trajectories across high school of per-occasion alcohol use and (b) the covariation of alcohol use and deviant friends over time., Method: In a longitudinal community sample (n = 374; 51% female), temperamental disinhibition, authoritarian and authoritative parenting, and parental alcohol use were assessed during childhood, and adolescents reported on alcohol use and affiliation with deviant friends in the spring of Grades 9, 10, 11, and 12., Results: Early parental alcohol use predicted the intercept of adolescent drinking. Subsequent patterns of adolescent alcohol use were predicted by sex and interactions of sex and childhood disinhibition with early authoritarian parenting. Additionally, childhood disinhibition interacted with parental alcohol use to moderate the covariation of drinking and deviant friends., Conclusions: These findings highlight early individual and contextual risk factors for alcohol use across high school, extending previous work and underscoring the importance of developmental approaches and longitudinal techniques for understanding patterns of growth in underage drinking.

Stress and associated alterations in hypothalamic-pituitary-adrenal (HPA) function have deleterious influence on the development of multiple mental and physical health problems. Prior research has aimed to identify individuals most at risk for the development of these stress-related maladies by examining factors that may contribute to inter-individual differences in HPA responses to acute stress. The objectives of this study were to investigate, in adolescents, (1) whether differences in neurocognitive abilities influenced cortisol reactivity to an acute stressor, (2) whether internalizing psychiatric disorders influenced this relationship, and (3) whether acute cognitive stress-appraisal mechanisms mediated an association between neurocognitive function and cortisol reactivity. Subjects were 70 adolescents from a community sample who underwent standardized neurocognitive assessments of IQ, achievement, and declarative memory measures at mean age 14 and whose physiological and behavioral responses to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) were assessed at mean age 18. Results showed that, among all adolescents, lower nonverbal memory performance predicted lower cortisol reactivity. In addition, internalizing disorders interacted with verbal memory such that the association with cortisol reactivity was strongest for adolescents with internalizing disorders. Finally, lower secondary cognitive appraisal of coping in anticipation of the TSST independently predicted lower cortisol reactivity but did not mediate the neurocognitive-cortisol relationship. Findings suggest that declarative memory may contribute to inter-individual differences in acute cortisol reactivity in adolescents, internalizing disorders may influence this relationship, and cognitive stress appraisal also predicts cortisol reactivity. Developmental, research, and clinical implications are discussed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Childhood and adolescent obesity have reached epidemic levels; however, little is known about the psychobiological underpinnings of obesity in youth and whether these differ from the mechanisms identified in adults. The current study examines concurrent (i.e., measured at the same point in time) and longitudinal (i.e., using earlier cortisol measures to predict later body mass index [BMI]) associations between diurnal cortisol and BMI across adolescence., Methods: Adolescent diurnal cortisol was measured over 3 days at each 11, 13, and 15 years. Hierarchical linear modeling was used to extract average measures of predicted morning, afternoon, evening levels of cortisol and the diurnal slope at each assessment. Adolescent BMI (kg/m(2)) was measured at 11, 13, 15, and 18 years. Sex, family socioeconomic status, mother's BMI, pubertal status, and adolescent mental health were examined as possible confounding variables., Results: Linear regressions revealed that blunted patterns of adolescent cortisol were associated with increased measures of BMI across adolescence both concurrently and longitudinally, particularly when examining measures of cortisol in early adolescence. Multinomial logistic regressions extended the linear regression findings beyond BMI scores to encompass categories of obesity., Conclusions: The current study builds on previous research documenting diurnal cortisol-obesity findings in adults by demonstrating similar findings exist both concurrently and longitudinally in adolescents. Findings suggest the association between cortisol and BMI is developmentally influenced and that blunted diurnal cortisol patterns can be identified in overweight individuals at a younger age than previously thought., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children's early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children's gender. To the authors' knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents' genomic DNA., (© 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.)

Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate through amygdala-ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

This study aimed to (1) identify a stable, trait-like component to cortisol and its circadian rhythm, and (2) investigate individual differences in developmental trajectories of HPA-axis maturation. Multiple salivary cortisol samples were collected longitudinally across four assessments from age 9 (3rd grade) through age 15 (9th grade) in a community sample of children (N = 357). Sophisticated statistical models examined cortisol levels and its rhythm over time; effects of age, puberty and gender were primarily considered. In addition to situation-specific and stable short-term or epoch-specific cortisol components, there is a stable, trait-like component of cortisol levels and circadian rhythm across multiple years covering the transition from childhood into adolescence. Youth had higher cortisol and flatter circadian rhythms as they got older and more physically developed. Girls had higher cortisol, stronger circadian rhythms, and greater developmental influences across adolescence. Distinguishing a stable, trait-like component of cortisol level and its circadian rhythm provides the empirical foundation for investigating putative mechanisms underlying individual differences in HPA functioning. The findings also provide important descriptive information about maturational processes influencing HPA-axis development., (Copyright © 2011 Wiley Periodicals, Inc.)

Myosin Va (myoV) is a processive molecular motor that transports intracellular cargo along actin tracks with each head taking multiple 72-nm hand-over-hand steps. This stepping behavior was observed with a constitutively active, truncated myoV, in which the autoinhibitory interactions between the globular tail and motor domains (i.e., heads) that regulate the full-length molecule no longer exist. Without cargo at near physiologic ionic strength (100 mM KCl), full-length myoV adopts a folded (approximately 15 S), enzymatically-inhibited state that unfolds to an extended (approximately 11 S), active conformation at higher salt (250 mM). Under conditions favoring the folded, inhibited state, we show that Quantum-dot-labeled myoV exhibits two types of interaction with actin in the presence of MgATP. Most motors bind to actin and remain stationary, but surprisingly, approximately 20% are processive. The moving motors transition between a strictly gated and hand-over-hand stepping pattern typical of a constitutively active motor, and a new mode with a highly variable stepping pattern suggestive of altered gating. Each head of this partially inhibited motor takes longer-lived, short forward (35 nm) and backward (28 nm) steps, presumably due to globular tail-head interactions that modify the gating of the individual heads. This unique mechanical state may be an intermediate in the pathway between the inhibited and active states of the motor.

We know very little about the development of rumination, the tendency to passively brood about negative feelings. Because rumination is a risk factor for many forms of psychopathology, especially depression, such knowledge could prove important for preventing negative mental health outcomes in youth. This study examined developmental origins of rumination in a longitudinal sample (N=337; 51% girls) studied in preschool (ages 3½ and 4½ years) and early adolescence (ages 13 and 15 years). Results indicated that family context and child temperament, assessed during the preschool period, were risk factors for a ruminative style in adolescence. Specifically, early family contexts characterised by over-controlling parenting and a family style of negative-submissive expressivity predicted higher levels of later rumination. These associations were moderated by children's temperamental characteristics of negative affect and effortful control. Further, the interaction of these temperament factors exerted an additional influence on later rumination. Implications for prevention and intervention efforts are discussed.

The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

Adolescent alcohol use is common and has serious immediate and long-term ramifications. While concurrent individual and context factors are robustly associated with adolescent alcohol use, the influence of early childhood factors, particularly in interaction with child sex, are less clear. Using a prospective community sample of 362 (190 girls), this study investigated sex differences in the joint influence of distal childhood and proximal adolescent factors on Grade 10 alcohol use. All risk factors and two-way early individual-by-context interactions, and interactions of each of these with child sex, were entered into the initial regression. Significant sex interactions prompted the use of separate models for girls and boys. In addition to the identification of early (family socioeconomic status, authoritative parenting style) and proximal adolescent (mental health symptoms, deviant friends) risk factors for both girls and boys, results highlighted important sex differences. In particular, girls with higher alcohol consumption at Grade 10 were distinguished by the interaction of early temperamental disinhibition and exposure to parental stress; boys with higher alcohol consumption at Grade 10 were distinguished primarily by early temperamental negative affect. Results have implications for the timing and type of interventions offered to adolescents.

Aggressive victims-children who are both perpetrators and victims of peer aggression-experience greater concurrent mental health problems and impairments than children who are only aggressive or only victimized. The stability of early identified aggressive victim status has not been evaluated due to the fact that most studies of aggressor/victim subgroups have focused on preadolescents and/or adolescents. Further, whether children who exhibit early and persistent patterns of aggression and victimization continue to experience greater mental health problems and functional impairments through the transition to adolescence is not known. This study followed 344 children (180 girls) previously identified as socially adjusted, victims, aggressors, or aggressive victims at Grade 1 (Burk et al. 2008) to investigate their involvement in peer bullying through Grade 5. The children, their mothers, and teachers reported on children's involvement in peer aggression and victimization at Grades 1, 3, and 5; and reported on internalizing symptoms, externalizing symptoms, inattention and impulsivity, as well as academic functioning, physical health, and service use at Grades 5, 7, and 9. Most children categorized as aggressive victims in Grade 1 continued to be significantly involved in peer bullying across elementary school. Children with recurrent aggressive victim status exhibited higher levels of some mental health problems and greater school impairments across the adolescent transition when compared to other longitudinal peer status groups. This study suggests screening for aggressive victim status at Grade 1 is potentially beneficial. Further early interventions may need to be carefully tailored to prevent and/or attenuate later psychological, academic, and physical health problems.

The moderating effects of biological sensitivity to context (physiological and behavioral stress reactivity) on the association between the early teacher-child relationship and the development of adolescent mental health problems were examined in a community sample of 96 children. Grade 1 measures of biological sensitivity to context included physiological (i.e., slope of mean arterial pressure across a 20- to 30-min stress protocol) and behavioral (i.e., temperamental inhibition/disinhibition) markers. Grade 1 measures of the teacher-child relationship included positive (i.e., closeness) and negative (i.e., conflict) qualities. Mental health symptoms were assessed at Grades 1 and 7. Results of a multiple regression analysis indicated substantial association of the teacher-child relationship with the development of adolescent mental health symptoms, especially for more reactive children. In addition to teacher-child relationship main effects, all four Reactivity x Teacher-Child Relationship interaction terms were statistically significant when controlling for Grade 1 symptom severity, suggesting that both physiological and behavioral reactivity moderate the association of both adverse and supportive aspects of the teacher-child relationship with Grade 7 symptom severity over and above Grade 1 severity. There were important differences, depending on which stress reactivity measure was considered. The importance of these findings for recent theoretical arguments regarding biological sensitivity to context and differential susceptibility is discussed.

Background: Experience in institutional/orphanage care has been linked to increased mental health problems. Research suggests that children adopted from institutions experience specific difficulties related to inattention/overactivity. Evidence of internalizing and conduct problems relative to non-adopted peers has been found in early childhood and early adolescence, but problems may not differ from other adopted children. This study clarifies the understanding of behavioral and emotional symptoms of post-institutionalized (PI) children during middle childhood., Methods: Eight- to eleven-year-old PI children (n=68) and two comparison groups, children internationally adopted from foster care (n=74) and non-adopted children (n=76), and their parents completed the MacArthur Health and Behavior Questionnaire related to attention-deficit/hyperactivity disorder (ADHD), externalizing, and internalizing symptoms. Group means for symptom level and number of children with symptoms above clinical cutoffs were compared., Results: PI children displayed an increased level of ADHD symptoms per parent report. PI child and parent report indicated a higher number of PI children above clinical ADHD cutoff. Both groups of internationally adopted (IA) children had higher levels of externalizing symptoms relative to non-adopted children, with parent report indicating higher numbers of IA children above the externalizing clinical threshold. Informants differed in their report of internalizing symptoms. Parents indicated that both IA groups displayed increased internalizing symptom levels and greater numbers above clinical threshold; however, children reported this to be true only for the PI group., Conclusions: PI children differ from non-adopted peers across symptom domains in middle childhood. Whether these concerns were more broadly associated with international adoption rather than institutional care depended on symptom domain and informant. An understanding of this variability may be beneficial for treatment and intervention., (© 2010 The Authors. Journal of Child Psychology and Psychiatry. © 2010 Association for Child and Adolescent Mental Health.)

This study utilized growth mixture modeling to examine the impact of parents, child care providers, teachers, and peers on the prediction of distinct developmental patterns of classroom externalizing behavior in elementary school. Among 241 children, three groups were identified. 84.6% of children exhibited consistently low externalizing behavior. The externalizing behavior of the Chronic High group (5.8%) remained elevated throughout elementary school; it increased over time in the Low Increasing group (9.5%). Negative relationships with teachers and peers in the kindergarten classroom increased the odds of having chronically high externalizing behavior. Teacher-child conflict increased the likelihood of a developmental pattern of escalating externalizing behavior. Boys were overrepresented in the behaviorally risky groups, and no sex differences in trajectory types were found., (Copyright © 2010 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.)

Changes in n-3 highly unsaturated fatty acids (HUFA, > or =20 carbons and > or =3 carbon-carbon double bonds) at baseline, during fish oil supplementation (4 weeks) and during washout (8 weeks) were compared in venous plasma, erythrocytes, whole blood and fingertip prick blood (weeks 0, 4, 8 and 12) with additional weekly fingertip prick samples. Correlations between the various blood fractions were slightly stronger when n-3 HUFA status was expressed as the percentage of n-3 HUFA in total HUFA as compared with the sum of EPA and DHA. Increases and decreases in n-3 HUFA were more dramatic in plasma, and EPA responded rapidly (within 1 week) with fish oil supplementation and cessation. Sex differences in the proportions of n-3 HUFA in blood were also apparent at baseline with females (n=7) having a tendency for higher docosahexaenoic acid (DHA, 22:6n-3) relative to eicosapentaenoic acid (EPA, 20:5n-3) and n-3 docosapentaenoic acid (DPAn-3, 22:5n-3) as compared with males (n=9). Further n-3 biomarker research in larger populations is required.