The Free Sign in morphea and other sclerosing disorders: A clue to the presence of early sclerosis?

BACKGROUND: The Floating Sign is a histopathologic clue to the diagnosis of autoimmune sclerosing skin disorders such as morphea and interstitial granulomatous dermatitis (IGD). On the other hand, the "free-floating" sign has been associated with neoplasms, for example, dermatofibroma and interstitial mycosis fungoides. Herein, we report the Free Sign in sclerosing skin disorders. METHODS: In a case-control study, we applied detailed histopathologic definitions of Floating Sign and Free Sign to assess their presence in morphea, IGD, and other sclerosing disorders. RESULTS: Free Sign was present in most cases of morphea (46/55, 84%) and IGD (7/13, 54%) but not necrobiosis lipoidica (NL) (6/14, 42.8%) or sclerodermoid graft versus host disease (SGVHD) (2/7, 28.5%). The sensitivity and specificity of Free Sign for morphea versus other disorders was 84% and 56%, respectively. Floating Sign was not identified in most cases: NL (3/14, 21.4%), SGVHD (1/7, 14.2%), morphea (5/55, 9%), IGD (1/13, 7.7%). The diagnostic sensitivity of Floating Sign in morphea was 9%. CONCLUSIONS: The Free Sign was present in most cases of morphea in our series and may represent a clue to the presence of evolving sclerosis. Free Sign may be seen in other sclerosing disorders. Technical artifact is a potential cause of a false-positive Free Sign.

Integrated Care for Pregnant and Parenting People With Substance Use.

Caring for pregnant people with substance use requires knowledge about specific substances used, treatment options, and an integrated, trauma-informed care team. This chapter will discuss crucial information for clinicians regarding evidence-based practice for screening, intervention, and ongoing support for pregnant people and their families impacted by substance use.

Behavioral Health Integration on Inpatient Obstetric Units: Program Development, Strategies for Implementation, and Lessons Learned.

Perinatal mood and anxiety disorders and substance use disorders are the primary causes of maternal mortality in the postpartum period and represent major public health concerns. Despite this, these conditions remain undertreated. Behavioral health integration in outpatient obstetric settings is necessary but insufficient to meet the needs of all patients. Inpatient behavioral health integration represents a promising avenue for addressing gaps in care. Results from recent program development indicate that needs assessment, stakeholder backing, collaboration with existing programs, and adaptability are key factors in successful implementation.

Perinatal Psychopharmacology: Innovative Approaches to Care Delivery.

Perinatal mental health conditions are the most common complications of childbirth and have well-established enduring negative effects. Obstetric (Ob) clinicians care for patients with perinatal mental health conditions across a spectrum of acuity, severity, and complexity. Ob and psychiatric clinicians can collaborate to create a cohesive continuum of psychopharmacologic care for perinatal patients. This chapter provides an overall framework for Ob-psychiatric clinician collaboration with examples of innovation in care delivery.

Setting Common Standards for Reproductive Psychiatry Education: Effectiveness of the National Curriculum in Reproductive Psychiatry.

OBJECTIVE: The National Curriculum in Reproductive Psychiatry (NCRP) provides standardized education for psychiatry residency training programs. The authors hypothesized that residents' preparedness to treat reproductive psychiatric concerns and their medical knowledge would improve following teaching with the NCRP. METHODS: Pre- and post-assessments were administered to residents enrolled in two waves of pilot NCRP training (Early-Modules and All-Modules). Data were collected by individual survey, and pre- and post-responses matched via anonymous ID. Statistical analyses were conducted using R version 3.5.3 and included paired Student's t-tests and a chi-square test. RESULTS: Thirty-eight residents completed the Early-Modules survey and 16 the All-Modules survey. In both groups, there was significant improvement in preparedness to treat pregnant and postpartum women with mental illness (p<0.05). Scores on the 29-point knowledge test rose by 2.5 points in the Early-Modules group and 4.3 points in the All-Modules group (p<0.001 for both). In both cohorts, a majority of residents felt reproductive psychiatry was among the top three specialties needed to become competent independent adult psychiatrists. CONCLUSIONS: Classroom training with local faculty using a standardized curriculum is feasible and results in substantial and significant improvements in both feelings of preparedness and medical knowledge. Psychiatry trainees view training in reproductive psychiatry as an important and missing aspect of their education. Dissemination of a standardized curriculum may help to forge a path toward subspecialty certification for reproductive psychiatry, and can be used as a model for other specialties.

Three genetic-environmental networks for human personality.

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.

Trauma-Informed Care for Obstetric and Gynecologic Settings.

PURPOSE: Trauma is common among those seeking Ob-Gyn care and may have pervasive impact on obstetrical and gynecological health, social functioning, and healthcare engagement. While guidelines exist on the detection and treatment of perinatal mood and anxiety disorders within Ob-Gyn care, the role of Ob-gyn clinicians in identifying and addressing patients' traumatic experiences and related symptoms is less clearly delineated. This manuscript provides an overview of trauma-related symptoms in the context of Ob-Gyn care and practical guidance of clinicians aiming to improve their detection and response to trauma in their clinical practice. DESCRIPTION: Posttraumatic stress disorder (PTSD) describes a psychiatric illness which develops as a response to a traumatic event. Women who have experienced trauma are also at increased risk for borderline personality disorder and other psychiatric comorbidities. Postpartum PTSD has particular relevance to obstetrical care. ASSESSMENT: Screening for trauma in Ob-Gyn care can provide an opportunity to address risk and offer targeted intervention. Several brief evidence-based screening tools are available. Individuals who screen positive require assessment of immediate safety and targeted referrals. Trauma informed care describes an approach to healthcare aimed to enhance physical and emotional safety for patients and clinicians. CONCLUSION: Given the prevalence and the potentially devastating and enduring impact of trauma and trauma-related symptoms, there is a critical need to address trauma within Ob-Gyn care. By recognizing the signs of trauma and initiating or referring to appropriate treatments, Ob-Gyn clinicians have a unique opportunity to better understand their patients and to improve their care.

Associations Between Adverse Childhood Experiences and Prenatal Mental Health and Substance Use Among Urban, Low-Income Women.

This study examined associations between Adverse Childhood Experiences (ACEs) and perinatal mental health and substance use among 98 low-income women (mean age 25.4 years; 93% Black/African American) referred to a mental health care manager in an urban women's clinic. Self-report and retrospective chart review data were utilized. Chi-squared and Fisher's Exact tests were performed to assess bivariate relationships between ACEs and mental health and substance use outcomes. Multivariate logistic regressions were used to examine the impact of ACEs on mental health and substance use, adjusting for marital status, education, and age. Findings indicate high levels of childhood adversity, specifically childhood abuse, are associated with negative perinatal mental health and substance use outcomes, including suicidal thoughts, anxiety, mood dysregulation, and tobacco and marijuana use. Inquiring about ACEs during prenatal care and/or in community health clinics may help identify patients' overall risk and provide opportunities for intervention for mothers and their infants.

Uncovering the complex genetics of human temperament.

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37-53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.

Uncovering the complex genetics of human character.

Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five clusters of people with distinct profiles of character traits regardless of genotype. Third, we found 42 SNP sets that identified 727 gene loci and were significantly associated with one or more of the character profiles. Each character profile was related to different SNP sets with distinct molecular processes and neuronal functions. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of 95% of the 42 SNP sets in healthy Korean and German samples, as well as their associations with character. The identified SNPs explained nearly all the heritability expected for character in each sample (50 to 58%). We conclude that self-regulatory personality traits are strongly influenced by organized interactions among more than 700 genes despite variable cultures and environments. These gene sets modulate specific molecular processes in brain for intentional goal-setting, self-reflection, empathy, and episodic learning and memory.

Review Article: Tools and trends for probing brain neurochemistry.

The brain is composed of complex neuronal networks that interact on spatial and temporal scales that span several orders of magnitude. Uncovering how this circuitry gives rise to multifaceted phenomena such as perception, memory, and behavior remains one of the grand challenges in science today. A wide range of investigative methods have been developed to delve deeper into the inner workings of the brain, spanning the realms of molecular biology, genetics, chemistry, optics, and engineering, thereby forming a nexus of discovery that has accelerated our understanding of the brain. Whereas neuronal electrical excitability is a hallmark property of neurons, chemical signaling between neurons-mediated by hundreds of neurotransmitters, neuromodulators, hormones, and other signaling molecules-is equally important, but far more elusive in its regulation of brain function for motor control, learning, and behavior. To date, the brain's neurochemical state has been interrogated using classical tools borrowed from analytical chemistry, such as liquid chromatography and amperometry, and more recently, newly developed fluorescent sensors. Here, the authors review advances in the development of functional fluorescent probes that are beginning to expand their understanding of the neurochemical basis of brain function alongside device-based analytical tools that have already made extensive contributions to the field. The emphasis herein is on the paradigms of probe and device development, which follow certain design principles unique to the interrogation of brain chemistry.

Effectiveness of an Interdisciplinary, Nurse Driven In-Hospital Code Stroke Protocol on In-Patient Ischemic Stroke Recognition and Management.

BACKGROUND: In-hospital strokes account for up to nearly 1 in 5 strokes. Clinical outcomes, such as length of stay, disability, and mortality are worse for in-hospital strokes than for those that occur in the community. For a variety of reasons, stroke can be more difficult to recognize and treat in hospitalized patients. Earlier recognition of stroke results in better clinical outcomes, presumably due to faster diagnosis and subsequently, prompt treatment. METHODS: This investigation was a retrospective, interrupted time series, observational study of all in-hospital stroke patients between 2008 and 2017. This investigation was a quality improvement project, and a waiver was granted from the institutional review board. We used Lean methodologies to standardize our stroke protocol and optimize skill-task alignment to improve the time from onset of symptoms to brain imaging (primary outcome). RESULTS: Overall, we observed significant improvement in the time from onset of symptoms to brain imaging from a median of 69 minutes to 37 minutes (P = .002). CONCLUSIONS: If successfully implemented, this approach may be useful in other care settings with potential to improve stroke outcomes, and decrease associated complications of stroke.

The "Line Sign" Is a Rapid and Efficient Diagnostic "Test" for Morphea: Clinicopathological Study of 73 Cases.

Histologic clues that facilitate rapid diagnosis of morphea at scanning magnification have been described but not well studied. We examined 73 cases of morphea and 42 control cases to determine the sensitivity and specificity of a novel histopathological feature-"the line sign (LS)"-a prominent, straight interface between subcutis and adjacent collagen. The sensitivity of LS was shown to be the most sensitive feature among 4 other existing histopathological features. Its specificity, however, was not the highest among the other features and needs to be evaluated further in future studies to confirm the usefulness of LS as a diagnostic tool for morphea.

Statistical Characterization of Human Brain Deformation During Mild Angular Acceleration Measured In Vivo by Tagged Magnetic Resonance Imaging.

Understanding of in vivo brain biomechanical behavior is critical in the study of traumatic brain injury (TBI) mechanisms and prevention. Using tagged magnetic resonance imaging, we measured spatiotemporal brain deformations in 34 healthy human volunteers under mild angular accelerations of the head. Two-dimensional (2D) Lagrangian strains were examined throughout the brain in each subject. Strain metrics peaked shortly after contact with a padded stop, corresponding to the inertial response of the brain after head deceleration. Maximum shear strain of at least 3% was experienced at peak deformation by an area fraction (median±standard error) of 23.5±1.8% of cortical gray matter, 15.9±1.4% of white matter, and 4.0±1.5% of deep gray matter. Cortical gray matter strains were greater in the temporal cortex on the side of the initial contact with the padded stop and also in the contralateral temporal, frontal, and parietal cortex. These tissue-level deformations from a population of healthy volunteers provide the first in vivo measurements of full-volume brain deformation in response to known kinematics. Although strains differed in different tissue type and cortical lobes, no significant differences between male and female head accelerations or strain metrics were found. These cumulative results highlight important kinematic features of the brain's mechanical response and can be used to facilitate the evaluation of computational simulations of TBI.

Reproductive Psychiatry Residency Training: A Survey of Psychiatric Residency Program Directors.

OBJECTIVE: The reproductive life cycle has unique influences on the phenotypic expression of mental illness in women. Didactic and clinical training focused on these sex-specific influences should be a vital component of the education of future psychiatrists. The authors sought to determine the current state of and attitudes toward reproductive psychiatry in resident education. METHODS: The authors administered a web-based survey to psychiatry residency training directors. They assessed the availability of both mandated and optional didactic and clinical training experiences in reproductive psychiatry. RESULTS: Fifty residency program directors answered the survey, for a response rate of 28%. More than half of residency program directors (59%) reported requiring some training in reproductive psychiatry. Both the breadth and depth of topics covered varied greatly among programs. Lack of time (48%) and lack of qualified faculty (26%) were the most frequently cited barriers to more training. Only 40% of residency directors surveyed agreed that all residents should be competent in reproductive psychiatry. CONCLUSIONS: These findings suggest that specific training in reproductive psychiatry is inconsistent in US residency programs, and that training that does exist varies considerably in clinical time and content. Given that women comprise more than 50% of all psychiatric patients and most women will menstruate, give birth, and undergo menopause, future psychiatrists would benefit from more systematic instruction in this area. The authors propose the development of a national, standardized reproductive psychiatry curriculum to address this gap and aid in producing psychiatrists competent to treat women at all stages of life.

Conditional Network Assembly and Targeted Protein Retention via Environmentally Responsive, Engineered ß-Roll Peptides.

Stimulus-responsive biomaterials have applications in many areas of biotechnology, such as tissue engineering, drug delivery, and bioelectrocatalysis. The intrinsically disordered repeat-in-toxin (RTX) domain is a conformationally dynamic peptide that gains ß-roll secondary structure when bound to calcium ions. A smart hydrogel platform was constructed by genetically fusing two rationally designed mutant RTX domains: first, a mutant peptide with hydrophobic interfaces capable of calcium-dependent network assembly, and second, another mutant that conditionally binds the model target protein lysozyme. In this way, the calcium-induced control over the secondary structure of the ß-roll peptide was exploited to regulate both the cross-linking and lysozyme-binding functionalities. The constructed biomaterial exhibited calcium-dependent gelation and target molecule retention, and erosion experiments showed that ß-roll peptides with a higher affinity for lysozyme produced more robust hydrogel networks. This work demonstrates the use of RTX domains for introducing two useful features simultaneously, network cross-linking and target protein binding, and that the calcium-dependent regulation of these systems can be useful for controlling bulk self-assembly and controlled release capabilities.

Genetic variations in taste perception modify alcohol drinking behavior in Koreans.

The sensory components of alcohol affect the onset of individual's drinking. Therefore, variations in taste receptor genes may lead to differential sensitivity for alcohol taste, which may modify an individual's drinking behavior. This study examined the influence of genetic variants in the taste-sensing mechanism on alcohol drinking behavior and the choice of alcoholic beverages. A total of 1829 Koreans were analyzed for their alcohol drinking status (drinker/non-drinker), total alcohol consumption (g/day), heavy drinking (≥30 g/day) and type of regularly consumed alcoholic beverages. Twenty-one genetic variations in bitterness, sweetness, umami and fatty acid sensing were also genotyped. Our findings suggested that multiple genetic variants modified individuals' alcohol drinking behavior. Genetic variations in the T2R bitterness receptor family were associated with overall drinking behavior. Subjects with the TAS2R38 AVI haplotype were less likely to be a drinker [odds ratio (OR): 0.75, 95% confidence interval (CI): 0.59-0.95], and TAS2R5 rs2227264 predicted the level of total alcohol consumption (p = 0.01). In contrast, the T1R sweet and umami receptor family was associated with heavy drinking. TAS1R3 rs307355 CT carriers were more likely to be heavy drinkers (OR: 1.53, 95% CI: 1.06-2.19). The genetic variants were also associated with the choice of alcoholic beverages. The homo-recessive type of TAS2R4 rs2233998 (OR: 1.62, 95% CI: 1.11-2.37) and TAS2R5 rs2227264 (OR: 1.72, 95% CI: 1.14-2.58) were associated with consumption of rice wine. However, TAS1R2 rs35874116 was associated with wine drinking (OR: 0.65, 95% CI: 0.43-0.98) and the consumption level (p = 0.04). These findings suggest that multiple genetic variations in taste receptors influence drinking behavior in Koreans. Genetic variations are also responsible for the preference of particular alcoholic beverages, which may contribute to an individual's alcohol drinking behavior.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

GWA meta-analysis of personality in Korean cohorts.

Personality is a determinant of behavior and lifestyle that is associated with health and human diseases. Despite the heritability of personality traits is well established, the understanding of the genetic contribution to personality trait variation is extremely limited. To identify genetic variants associated with each of the five dimensions of personality, we performed a genome-wide association (GWA) meta-analysis of three cohorts, followed by comparison of a family cohort. Personality traits were measured with the Revised NEO Personality Inventory for the five-factor model (FFM) of personality. We investigated the top five single-nucleotide polymorphisms (SNPs) for each trait, and revealed the most highly association with neuroticism and TACC2 (rs1010657, P=8.79 × 10(-7)), extraversion and PTPN12 (rs12537271, P=1.47 × 10(-7)), openness and IMPAD1 (rs16921695, P=5 × 10(-8)), agreeableness and RPS29 (rs8015351, P=1.27 × 10(-6)) and conscientiousness and LMO4 (rs912765, P=2.91 × 10(-6)). It had no SNP reached the GWA study threshold (P<5 × 10(-8)). When expanded the SNPs up to top 100, the correlation of PTPRD (rs1029089) and agreeableness was confirmed in Healthy Twin cohort with other 13 SNPs. This GWA meta-analysis on FFM personality traits is meaningful as it was the first on a non-Caucasian population targeted to FFM of personality traits.