Novel Approaches to Patients with Differences of Sex Development.

Patients with differences of sex development (DSDs) have complex anatomy and surgical needs related to both Mullerian and non-Mullerian structures. Approaches to vaginal reconstruction for these conditions are guided by individual anatomy, with the goal of establishing unobstructed outflow for the reproductive, urinary, and gastrointestinal tracts. Patients may have anatomy requiring vaginoplasty for either outflow tract obstruction or chosen sexual function. In this article, the authors focus on management of differences in vaginal anatomy with delayed vaginoplasty for the newborn with DSD.

Are Functional Performance Test Scores Better When Compared to Baseline or Contralateral Limb Scores Following LE Injury in Adolescent Athletes?

Background: Functional performance tests (FPT) have been used with athletes following an injury to determine readiness to return-to-play (RTP), usually using limb symmetry indices to the contralateral limb or a baseline score. There is not a consensus as to which criterion scores are best compared. Hypothesis/Purpose: This study aimed to compare common functional performance test scores from injured athletes at the time of release to RTP to both preseason baseline scores and to the contralateral limb. It was hypothesized that using baseline scores for comparison would be more responsive to residual deficits following injury than using the contralateral limb. Study Design: Prospective longitudinal cohort study. Methods: High school athletes (n=395) from all varsity sports completed a battery of FPTs including the Y-Balance Test (YBT), single limb hop tests and T-Test for agility (TT) during their preseason to establish baseline data. Injured athletes (n=19) were re-tested using all FTP's again at the time of RTP. Paired t-tests were used to detect if significant (p\<0.05) residual deficits were present at time of RTP when compared to baseline and to contralateral scores on FPTs. Results: Differences in YBT scores were found in the anterior direction only (p=0.021) when comparing RTP to preseason, but there were no differences when compared to RTP data for the contralateral limb. Differences were detected with the single leg hop test (p = 0.001) when comparing the RTP to preseason and were also detected in both the single leg hop (p= 0.001) and triple hop (p=0.018) when compared to the contralateral limb. Differences in TT scores were detected when comparing RTP to preseason for cutting first with both the unaffected (p = 0.019) and affected (p = 0.014) limbs. Conclusions: The YBT in the anterior direction and the TT are better able to detect residual deficits when comparing RTP to preseason scores. Hop tests are better able to detect deficits when compared to the contralateral limb. These results could make preseason testing more efficient when creating a reference for determining RTP readiness following lower extremity injury.

Chemistry in the mail: Stamps from around the globe and public science communication in the twentieth century.

Postage stamps are designed to convey messages that reverberate symbolically with broad swaths of the public, and their content has been employed as a window into how members of the public understand the ideas represented therein. In this rhetorical analysis, we analyze Philadelphia's Science History Institute's Witco Stamp Collection, which features 430 stamps from countries around the globe dating from 1910 to 1983, to identify how chemistry is portrayed in this ubiquitous medium. We find the vernacular of science reflected and supported by these images functions to (a) define chemistry in terms of its invisibility and abstraction; (b) uphold chemical operations as instrumental and daedal, or exceptional, in nature; and (c) delineate practitioners of chemistry as-on the whole-privileged and preternatural. Our findings reveal some of the overarching communicative tools made available to twentieth-century non-experts for articulating chemistry as an enterprise and reveal how those tools positioned chemistry in terms of values related to opacity and exclusivity.

Resident Education Curriculum in Pediatric and Adolescent Gynecology: The Short Curriculum 3.0.

Exposure to pediatric and adolescent gynecology (PAG) varies across residency programs in obstetrics and gynecology, family medicine, and pediatrics, as well as fellowship programs in adolescent medicine. Nevertheless, these programs are responsible for training residents and fellows and providing opportunities within their programs to fulfill PAG learning objectives. To that end, the North American Society for Pediatric and Adolescent Gynecology has taken a leadership role in PAG education by creating and systematically updating the Short Curriculum. This curriculum outlines specific learning objectives that are central to PAG education and lists essential resources for learners' reference. This updated curriculum replaces the previous 2018 publication with added content, resources, and updated references.

Medicalization's Communicative Infrastructure: Seventy Years of "Brain Chemistry" in the New York Times.

Medicalization theory aims to delineate how and why non-medical issues become demarcated within the realm of medical jurisdiction. The theory postulates that medicalization is marked by diagnostic naming, medical expertise, technological standardization and the de-contextualization of experiential knowledge, and that it is driven by popular media and lay discourse as much as by the communication of health professionals and medical institutions. Although medicalization has been recognized as an inherently rhetorical act, medicalization theory does not attend to the specific communicative means undergirding its orchestration. Drawing from medicalized New York Times coverage of the phrase "brain chemistry" (N = 71), we address this theoretical aperture, identifying through rhetorical analysis the most common communicative devices that emerged across 70 years of coverage and three distinct diagnoses (i.e., mental illness, addiction and overweight/obesity). Our findings reveal three central rhetorical means through which medicalization is communicated including mechanical metaphor, pedagogy of contrast, and moral enthymeme. By tracing content across time, the current study explicates the communicative infrastructure that gives rise to medicalization, thereby extending the literature from questions of why medicalization occurs and what its content is to how it is conveyed and imparted.

Bleeding Patterns among Adolescents Using the Levonorgestrel Intrauterine Device: A Single Institution Review.

STUDY OBJECTIVE: To describe the bleeding patterns associated with the use of the levonorgestrel intrauterine device (IUD) in adolescents. DESIGN, SETTING, AND PARTICIPANTS: A retrospective chart review of postmenarchal adolescent patients ages 8-19 years who had the levonorgestrel IUD inserted at Phoenix Children's Hospital from 2012 to 2018. INTERVENTIONS: Insertion of the 52-mg and 13.5-mg levonorgestrel IUD. MAIN OUTCOME MEASURES: The rate of amenorrhea and other bleeding patterns after insertion of the levonorgestrel IUD and the factors that might predict those bleeding patterns. RESULTS: A total of 260 charts were identified with 221/260 (85.0%) patients choosing the 52-mg IUD and 39/260 (15.0%) patients choosing the 13.5-mg IUD to be inserted. Follow-up data were available for 166 patients. The overall rate of amenorrhea among IUD users was 39.8% (n = 66) with no difference between 52-mg and 13.5-mg IUD users (P = .656). Regularity and flow of menstrual cycle, history of bleeding disorder, history of developmental delay, and current treatment with testosterone for gender dysphoria before IUD insertion did not appear to have a significant effect on the rate of amenorrhea or bleeding patterns post-IUD insertion. CONCLUSION: The levonorgestrel IUD can be successfully used to control abnormal uterine bleeding and suppress menses in adolescents. Menstrual cycle characteristics pre-IUD insertion did not result in predictable post-IUD bleeding patterns.

Psychometric properties of the Spanish version of the Experience of Caregiving Inventory (ECI) among caregivers of individuals with an eating disorder.

PURPOSE: The aim of this study was to examine the psychometric properties of the Spanish version of the Experience of Caregiving Inventory (ECI-S), which is designed to assess the caregiver's appraisal of the impact of caring for a relative with a serious mental illness. METHODS: A cross-sectional study was conducted among 320 caregivers of a relative with an eating disorder to examine: (a) descriptive statistics; (b) internal consistency reliability; (c) the fit of the original ten-factor structure of the ECI through exploratory factor analysis, using a semi-confirmatory approach, for each subscale individually, and (d) concurrent validity. A total of 307 caregivers completed the scale. RESULTS: Reliability of the ECI subscales scores was acceptable (α = 0.63-0.89). Results replicated the original ten-factor structure of the instrument. The concurrent validity was supported by correlations of the ECI-negative subscale with psychological distress (GHQ-12, 0.43), and with depression and anxiety (HADS, 0.48 and 0.49, respectively). CONCLUSIONS: The Spanish version of the ECI (ECI-S) demonstrated good psychometric properties in terms of validity and reliability that were similar to the original version. It is an acceptable and valid instrument for assessing the impact on family members of caring for a relative with an eating disorder and can be recommended for use in clinical settings in Spain. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Pelvic pain in patients with complex mullerian anomalies including Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH), obstructed hemi-vagina ipsilateral renal anomaly (OHVIRA), and complex cloaca.

Caring for patients with congenital pelvic anomalies can be challenging in many ways but one crucial aspect is providing longitudinal into adulthood. Newborns with urinary, intestinal or vaginal obstruction require urgent operations to relieve obstruction followed by multiple reconstructive procedures involving the perineum. Openings are created in the pelvic floor musculature that did not exist in development. Adolescence presents further challenges for these postoperative patients while other diagnoses present for the first time in the peri-pubertal teenage years. Young adults can have new symptoms when they become sexually active and are faced with reproductive decisions. During all of these time periods, optimization of function is of paramount importance and patients who are suffering are not able to participate in school, sports or work. This study evaluates the prevalence of pelvic pain in newborns and adolescents with complex congenital pelvic anomalies, associated factors and possible treatment options.

Current Low-Cost Video-Based Motion Analysis Options for Clinical Rehabilitation: A Systematic Review.

BACKGROUND: Physical therapists, as clinical human movement experts, must qualitatively evaluate patients' functional and biomechanical impairments. There are now low-cost 2- and 3-dimensional video measurement systems that can be used to increase the precision and reliability of these qualitative clinical assessments. PURPOSE: The purpose of this study was to systematically review current low-cost video-based methods for motion analysis compared with gold-standard 3-dimensional biomechanical methods. DATA SOURCES: Electronic searches were conducted until January 2018 within the following databases: MEDLINE via PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Scopus, and the Institute of Electrical and Electronics Engineers. STUDY SELECTION: Studies designed to evaluate criterion-referenced validity and/or reliability of video-based motion analysis technologies within the last 20 years were included. English-language articles dealing with human rehabilitation were considered. DATA EXTRACTION: Data extraction was independently completed by 3 reviewers, and methodological quality was assessed using the 2018 Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. Articles were organized for analysis on the basis of type of motion analyzed and category of each low-cost technology used. DATA SYNTHESIS: With 20 articles meeting selection criteria, 10 low-cost motion analysis platforms were presented, each examining different functional movement-dependent variables. Overall article quality was "low" or "very low" on the basis of Consensus-Based Standards for the Selection of Health Measurement Instruments scoring. Correlations between low-cost and 3-dimensional gold standard systems ranged widely from "poor" agreement (r = 0.025) to "strong" agreement (r = 0.992). Spatiotemporal gait parameters consistently outperformed planar joint angle data. Reliability was better measured than concurrent validity. A summary table was developed to assist clinicians in choosing which motions could potentially be measured accurately by each low-cost platform on the basis of current findings. LIMITATIONS: Databases available to researchers were more clinical/medical in nature, and this review was written from that clinically based perspective. Lack of standardized protocols and methodology within included studies was common, making generalizability difficult. CONCLUSIONS: Research attempting to validate newer low-cost movement analysis systems is limited in quality. Measurement of only certain variables should be considered when these tools are used. Further research is warranted, because these devices still have potential clinical utility for supplementing qualitative movement assessment with objective outcome measures.

Development of a Mobile Motion Capture (MO2CA) System for Future Military Application.

State-of-the-art three-dimensional motion analysis systems, which are utilized to predict, diagnose, and treat many musculoskeletal and neurological disorders, are expensive and space consuming. These systems have only been widely used in large research facilities because of their lack of this transportability. Since device portability is a critically important in the military, most small military hospitals are therefore deprived of these systems. The purpose of this study was to develop a mobile motion capture system, MO2CA, to automatically detect the movement of the human body. Twenty healthy young adults participated in this study. Colored tape was attached on the heel, and subjects walked on the treadmill at three different speeds: preferred, fast, and slow. Two motion capture systems were used concurrently: Qualisys (100 Hz) and MO2CA (60 Hz). Four dependent variables were: stride length, stride time, stride length variability, and stride time variability. Paired t-tests, Pearson correlation, and Bland-Altman plots were used to investigate the statistical differences between two systems. No significant differences were found for all dependent variables. Regression and Bland-Altman plots showed strong agreements between the two systems. Our MO2CA shows a potential for real-time tracking of biomechanical changes in gait, which is extremely important for military use.

A controlled study of the Collaborative Care Skills Workshops versus Psycho-educational Workshops among Spanish caregivers of relatives with an eating disorder.

The aim of this study was to test the hypothesis that a negative reaction to the illness would be reduced through the "Collaborative Care Skills Workshops" programme among Spanish caregivers of relatives with an eating disorder. Caregivers were randomly allocated to either the skill-based workshops (n = 32) or psycho-educational workshops (n = 31), and assessments were carried out over time (T0 vs. T1 vs. T2 ). There were no significant differences between interventions on primary or secondary caregiver outcomes or among the patients themselves. However, caregivers in both interventions showed greater improvement at T2 on accommodating and enabling behaviours and an improvement at T1 in terms of psychological distress and appraisals towards the caregiving experience. Eating pathology, psychological distress, and some indices of psychosocial adjustment were significantly lower among the patients following both interventions (T1 ). Overall, both interventions may be able to help caregivers and patients to decrease their psychological distress. HIGHLIGHTS: Involvement of family members in the treatment could be the best resource for aiding in their relative's recovery. This is the first controlled study to test the effectiveness of the Collaborative Care Skills Workshops in Spanish caregivers. Both interventions could be implemented as both help Spanish caregivers and patients.

Trends in the Management of Nonviable Pregnancies of Unknown Location in the United States.

BACKGROUND: When managing a nonviable pregnancy of unknown location (PUL), a debate has emerged in the literature whether to perform uterine curettage for definitive diagnosis of pregnancy location or administer methotrexate for a presumed ectopic pregnancy. The purpose of this study is to describe the treatment patterns when managing a PUL. METHODS: A prospective, anonymous Internet based-electronic survey of PUL case scenarios was administered to a random sample of physicians across the United States. RESULTS: A total of 214 physicians responded. When presented with a PUL by ultrasound and a ßhCG measurement of 3,270 mIU/mL, which is above the discriminatory level, 88.3% (188) would choose an additional ßhCG measurement before recommending any intervention. When presented with a PUL by ultrasound and serial ßhCG measurements demonstrating an inappropriate trend for a viable gestation, 36.5% would offer uterine curettage and 31.3% would offer methotrexate. Resident and private clinicians had a fourfold lower adjusted odds of choosing uterine curettage compared to academic physicians. CONCLUSIONS: Based on our findings, there does not appear to be a consensus regarding the management of a PUL.

Public Perception of Female Fertility: Initial Fertility, Peak Fertility, and Age-Related Infertility Among U.S. Adults.

Perceptions of fertility are thought to impact reproductive behaviors, yet little is known about how lay people conceptualize the female fertility timeline. In this research, public perception of the female fertility timeline was assessed via a national survey of U.S. adults (N = 990) ranging in age from 18 to 89 years. Although there is no scientific consensus on the makeup of the female fertility timeline, results from this research indicate that the U.S. public posits fertility onset at (approximately) 13 years, peak fertility at 22, ideal first pregnancy age at 23, too late for pregnancy at 46, and infertility at 49. Regression analysis revealed that perceived peak fertility and ideal pregnancy age were positively correlated such that participants perceived the ideal pregnancy age as directly following peak fertility. Education was significantly related to fertility perceptions; those with more education perceived initial fertility to be lower and peak fertility and ideal pregnancy age to be higher. In other words, more highly educated individuals perceived fertility to manifest over a longer period of time as compared to individuals with less education. Black and Hispanic participants and participants with lower income perceived ideal first pregnancy age as significantly lower than did White participants and participants with higher income. These differences may suggest that the seeds of health disparities associated with phenomena such as adolescent pregnancy are lurking in fertility timeline perceptions.

SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors.

Most anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung tumors initially respond to small-molecule ALK inhibitors, but drug resistance often develops. Of tumors that develop resistance to highly potent second-generation ALK inhibitors, approximately half harbor resistance mutations in ALK, while the other half have other mechanisms underlying resistance. Members of the latter group often have activation of at least one of several different tyrosine kinases driving resistance. Such tumors are not expected to respond to lorlatinib-a third-generation inhibitor targeting ALK that is able to overcome all clinically identified resistant mutations in ALK-and further therapeutic options are limited. Herein, we deployed a shRNA screen of 1,000 genes in multiple ALK-inhibitor-resistant patient-derived cells (PDCs) to discover those that confer sensitivity to ALK inhibition. This approach identified SHP2, a nonreceptor protein tyrosine phosphatase, as a common targetable resistance node in multiple PDCs. SHP2 provides a parallel survival input downstream of multiple tyrosine kinases that promote resistance to ALK inhibitors. Treatment with SHP099, the recently discovered small-molecule inhibitor of SHP2, in combination with the ALK tyrosine kinase inhibitor (TKI) ceritinib halted the growth of resistant PDCs through preventing compensatory RAS and ERK1 and ERK2 (ERK1/2) reactivation. These findings suggest that combined ALK and SHP2 inhibition may be a promising therapeutic strategy for resistant cancers driven by several different ALK-independent mechanisms underlying resistance.

Experience of caregiving and coping strategies in caregivers of adolescents with an eating disorder: A comparative study.

Caring for a relative with an eating disorder (ED) is associated with heightened psychological distress, which, according to a stress-coping model, may be influenced by coping and appraisal. However, limited quantitative studies have assessed coping in ED caregivers. This cross-sectional study aims to assess 1) the differences in coping between caregivers of three groups: patients with an ED, patients with a substance use disorder, and healthy teens, and 2) the patient and caregiver variables associated with coping and appraisal of the caregiving experience. A one-way MANOVA was significant for caregiver group for mothers, but not fathers. Mothers of both patient groups used more self-sufficient problem focused coping than mothers of healthy teens. Patient caregivers did not significantly differ from caregivers of healthy teens in their use of avoidance. Mothers used social support strategies more than fathers. A positive experience of caregiving was significantly associated with the use of approach-oriented coping in ED caregivers and a negative experience of caregiving was significantly associated with avoidance in ED mothers. Older ED caregivers were less likely to use avoidance. Future interventions could help ED caregivers to recognize their coping preferences and how to appropriately use these strategies when faced with illness-related stressors.

Primary Patient-Derived Cancer Cells and Their Potential for Personalized Cancer Patient Care.

Personalized cancer therapy is based on a patient's tumor lineage, histopathology, expression analyses, and/or tumor DNA or RNA analysis. Here, we aim to develop an in vitro functional assay of a patient's living cancer cells that could complement these approaches. We present methods for developing cell cultures from tumor biopsies and identify the types of samples and culture conditions associated with higher efficiency of model establishment. Toward the application of patient-derived cell cultures for personalized care, we established an immunofluorescence-based functional assay that quantifies cancer cell responses to targeted therapy in mixed cell cultures. Assaying patient-derived lung cancer cultures with this method showed promise in modeling patient response for diagnostic use. This platform should allow for the development of co-clinical trial studies to prospectively test the value of drug profiling on tumor-biopsy-derived cultures to direct patient care.

Emotion Regulation in Binge Eating Disorder: A Review.

The purpose of the present review is to provide a summary of the research findings on emotion regulation in Binge Eating Disorder (BED). Negative emotions and maladaptive emotion regulation strategies play a role in the onset and maintenance of binge eating in BED. Anger and sadness, along with negative emotions related to interpersonal experiences (i.e., disappointment, being hurt or loneliness), seem to be particularly relevant. Individuals with BED have a tendency to suppress and ruminate on their unwanted emotions, which leads to increased psychopathological thoughts and symptoms. Compared to healthy controls, they use adaptive strategies, such as reappraisal, less frequently. Evidence concerning the causal relation between negative affect and binge eating is inconclusive and still very limited. While experimental studies in a laboratory setting lack ecological validity, ecological momentary assessment studies offer more promise at unraveling the causal relationship between emotions and binge eating. Increases in negative affect are found to be antecedents of binge eating in BED. However, there seems to be less support for the possibility that binge eating serves as a means to alleviate negative affect. Finally, BED seems to be related to other forms of maladaptive emotion regulation strategies, such as substance abuse and self-harm.

Examining Maternal Psychopathology, Family Functioning and Coping Skills in Childhood Obesity: A Case-Control Study.

The shared family environment is an important risk factor in the development of childhood obesity. This study aims to examine differences in maternal psychopathology, family functioning, expressed emotion and coping skills between families of a child with obesity and those with a normal-weight child. This case-control study consisted of 50 mothers with a child (age 8-12 years) with obesity (p ≥ 97) and a control group of 50 mothers of a child with normal weight (p < 85), matched for age, sex and socio-economic status. Compared with families with normal-weight children, those with children with obesity showed significant differences in levels of trait anxiety, criticism and over-protectiveness, and maladaptive coping skills. Structural equation modelling revealed that the mothers' psychopathology predicted children's body mass index (BMI) z-scores through expressed emotion and maladaptive coping scores. There were significant direct and indirect relations among maternal BMI, psychopathology, expressed emotion and coping, which all together explained 26.5% of variance of children's BMI z-scores. Considering this relation between maternal variables and child weight status, childhood obesity intervention programs may benefit from targeting maternal BMI, psychopathology, expressed emotion and coping skills. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Psychiatric comorbidity and maternal distress among adolescent eating disorder patients: A comparison with substance use disorder patients.

High rates of comorbidity are found among eating disorder (ED) patients, which may negatively affect treatment outcome and prognosis. However, there is a shortage of studies in Spain using clinician administered interviews to assess rates of comorbidity among these patients, particularly in adolescents. This study aimed to evaluate Axis I psychiatric diagnoses in adolescent patients with an ED and to compare them with patients with a distinct disorder with adolescent onset, substance use disorder (SUD) patients. Considering that maternal psychological distress is another factor involved in ED prognosis, a secondary aim was to examine the relationship between patient's psychological variables and maternal distress (depression and anxiety). The cross-sectional study included 50 ED patients, 48 SUD patients, and their mothers. More than half of the patients received a diagnosis for a comorbid disorder. Internalizing problems were more common among EDs and externalizing disorders were the most common comorbidities among SUDs, similar to findings from other countries. Maternal distress was associated with higher levels of depression and symptom severity in patients. No differences in distress were found between mothers of patients with a comorbid diagnosis and those without. Elevated anxiety or depression in mothers did not increase the likelihood of patients having a particular primary diagnosis. In short, while both ED and SUD patients presented high rates of comorbidity, the types of comorbid diagnoses were specific to each group. Assessing for the presence of comorbid disorders and targeting maternal psychological distress may guide treatment interventions and improve patient prognosis.

Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer.

Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALKG1202R, increases significantly after treatment with second-generation agents. To investigate strategies to overcome resistance to second-generation ALK inhibitors, we examine the activity of the third-generation ALK inhibitor lorlatinib in a series of ceritinib-resistant, patient-derived cell lines, and observe that the presence of ALK resistance mutations is highly predictive for sensitivity to lorlatinib, whereas those cell lines without ALK mutations are resistant. SIGNIFICANCE: Secondary ALK mutations are a common resistance mechanism to second-generation ALK inhibitors and predict for sensitivity to the third-generation ALK inhibitor lorlatinib. These findings highlight the importance of repeat biopsies and genotyping following disease progression on targeted therapies, particularly second-generation ALK inhibitors. Cancer Discov; 6(10); 1118-33. ©2016 AACRSee related commentary by Qiao and Lovly, p. 1084This article is highlighted in the In This Issue feature, p. 1069.