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Fibroblast growth factor (FGF) signaling is known to play an important role in lung organogenesis. However, we recently demonstrated that FGF10 fails to induce branching in human fetal lungs as is observed in mouse. Our previous human fetal lung RNA sequencing data exhibited increased FGF18 during the pseudoglandular stage of development, suggestive of its importance in human lung branching morphogenesis. Whereas it has been previously reported that FGF18 is critical during alveologenesis, few studies have described its implication in lung branching, specifically in human. Therefore, we aimed to determine the role of FGF18 in human lung branching morphogenesis. Human fetal lung explants within the pseudoglandular stage of development were treated with recombinant human FGF18 in air-liquid interface culture. Explants were analyzed grossly to assess differences in branching pattern, as well as at the cellular and molecular levels. FGF18 treatment promoted branching in explant cultures and demonstrated increased epithelial proliferation as well as maintenance of the double positive SOX2/SOX9 distal bud progenitor cells, confirming its role in human lung branching morphogenesis. In addition, FGF18 treated explants displayed increased expression of SOX9, FN1, and COL2A1 within the mesenchyme, all factors that are important to chondrocyte differentiation. In humans, cartilaginous airways extend deep into the lung up to the 12th generation of branching whereas in mouse these are restricted to the trachea and main bronchi. Therefore, our data suggest that FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells.

In 2008, the Veterans Health Administration (VHA) established a suicide high-risk flag (HRF) for patient records. To inform ongoing suicide prevention activities as part of operations and quality improvement work in the U.S. Department of Veterans Affairs, the authors evaluated suicide risk following HRF activations and inactivations.For annual cohorts of VHA users, HRF receipt and demographic and clinical care contexts in the 30 days before HRF activations were examined for 2014-2016 (N=7,450,831). Veterans were included if they had VHA inpatient or outpatient encounters during the index or previous year. Suicide rates in the 12 months after HRF activations and inactivations were assessed. Using multivariable Cox proportional hazards regression, the authors compared suicide risk following HRF activation and inactivation with veterans without HRFs, adjusted for age, gender, and race-ethnicity.HRF activation (N=47,015) was commonly preceded within 30 days by a documented suicide attempt (39.5%) or inpatient mental health admission (40.1%). Suicide risk was elevated in the 12 months after flag activation (crude suicide rate=682 per 100,000 person-years, adjusted hazard ratio [HR]=21.00, 95% confidence interval [CI]=18.55-23.72) compared with risk among VHA users without HRF activity. Risk after HRF inactivation (N=41,251) was also elevated (crude suicide rate=408 per 100,000 person-years, adjusted HR=12.43, 95% CI=10.57-14.63) compared with risk among VHA users without HRF activity.Suicide risk after HRF activation was substantially elevated and also high after HRF inactivation. Findings suggest the importance of comprehensive suicide risk mitigation and support recent VHA process enhancements to formalize inactivation criteria and support veterans after HRF inactivation.

Introduction Little is known regarding long-term mortality outcomes after non-fatal suicide attempts among Veterans Health Administration (VHA) patients, which may inform services delivery and program evaluation. Methods For 4,601,081 Veterans with 2005 VHA encounters, we assessed unadjusted and age-adjusted all-cause and cause-specific mortality through 2017, overall and for Veterans with (N = 8243) versus without (N = 4,592,838) 2005 VHA suicide attempt documentation. Standardized mortality ratios compared mortality rates by suicide attempt status. Multivariable proportional hazards regression models assessed age- and gender-adjusted mortality risk. Results Among Veteran VHA users with non-fatal suicide attempt diagnoses, 1.6% died of suicide, 4.6% of non-suicide external causes, and 30.7% of any cause. In age- and gender-adjusted analyses, Veterans who attempted suicide had increased suicide (hazard ratio [HR] = 4.52, 95% confidence interval [CI] = 3.82-5.36), non-suicide external cause (HR = 3.75, 95% CI = 3.38-4.17), and all-cause (separate due to non-proportional hazards: 2006, HR = 2.05, 95% CI = 1.81-2.31; 2007-2017, HR = 1.72, 95% CI = 1.65-1.80) mortality through 2017. Conclusion Over 12 years, Veteran VHA patients with non-fatal suicide attempt diagnoses had increased risk of suicide, non-suicide external cause, and all-cause mortality. Over 98% of Veteran VHA users who had a diagnosed non-fatal attempt did not die by suicide, highlighting additional program evaluation outcomes and opportunities to support physical and mental health.

Child sexual abuse (CSA) has lasting, detrimental impacts but remains under addressed. Primary care is well positioned to address CSA. This qualitative study explored addressing CSA in primary care. Three semistructured focus groups were conducted at community practices with above average poverty and family instability. Provider and staff experiences were using thematic analysis from a social ecology perspective. Processes among primary care, families, and the community are represented in the Primary Care SAFR Model. Findings highlight multilevel challenges managing CSA. Comprehensive training, uniform and focused assessment and response, improved response system policies and support, and integrated care facilitate addressing CSA in primary care.

Individuals with mental or substance use disorders have higher mortality rates than people in the general population. How excess mortality varies across health care facilities is unknown. The authors sought to investigate facility-level mortality rates among Veterans Health Administration (VHA) patients who had received diagnoses of mental or substance use disorders.An electronic medical records-based retrospective cohort study was conducted, encompassing 8,812,373 unique users of 139 VHA facilities from 2011 to 2016. Covariates included age, sex, and past-year diagnoses of serious mental illness, posttraumatic stress disorder, major depressive disorder, other mental health conditions, or substance use disorders. The outcome was all-cause mortality per comprehensive Veterans Affairs/Department of Defense searches of the National Death Index. Proportional hazards regression was used to calculate overall and facility-specific hazard ratios (HRs) for each diagnosis group, adjusted for age, sex, and comorbid medical conditions.Overall, all-cause mortality was statistically significantly elevated among VHA users with mental health diagnoses (HR=1.21, 95% confidence interval=1.20-1.22). HRs varied across facilities consistently over time. At the VHA facility level, diagnostic groups were significantly correlated with the degree of excess mortality. Results were similar in sensitivity analyses that excluded deaths from suicide or drug or alcohol overdose.VHA users with mental or substance use disorder diagnoses had elevated mortality rates. Correlation in excess mortality across two periods indicated that facility differences in excess mortality were persistent and therefore potentially associated with facility- and community-level factors, which may help inform quality improvement efforts to reduce mortality rates.

Bud tip progenitors (BTPs) in the developing lung give rise to all epithelial cell types found in the airways and alveoli. This work aimed to develop an iPSC organoid model enriched with NKX2-1+ BTP-like cells. Building on previous studies, we optimized a directed differentiation paradigm to generate spheroids with more robust NKX2-1 expression. Spheroids were expanded into organoids that possessed NKX2-1+/CPM+ BTP-like cells, which increased in number over time. Single cell RNA-sequencing analysis revealed a high degree of transcriptional similarity between induced BTPs (iBTPs) and in vivo BTPs. Using FACS, iBTPs were purified and expanded as induced bud tip progenitor organoids (iBTOs), which maintained an enriched population of bud tip progenitors. When iBTOs were directed to differentiate into airway or alveolar cell types using well-established methods, they gave rise to organoids composed of organized airway or alveolar epithelium, respectively. Collectively, iBTOs are transcriptionally and functionally similar to in vivo BTPs, providing an important model for studying human lung development and differentiation.

Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively collected longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS) (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala–PFC connectivity during angry face processing.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

Prominent theories suggest that disruptions in amygdala reactivity and connectivity when processing emotional cues are key to the etiology of youth antisocial behavior (AB) and that these associations may be dependent on co-occurring levels of callous-unemotional (CU) traits. We examined the associations among AB, CU traits, and amygdala reactivity and functional connectivity while viewing emotional faces (fearful, angry, sad, happy) in 165 adolescents (46% male; 73.3% African American) from a representative, predominantly low-income community sample. AB was associated with increased amygdala activation in response to all emotions and was associated with greater amygdala reactivity to emotion only at low levels of CU traits. AB and CU traits were also associated with distinct patterns of amygdala connectivity. These findings demonstrate that AB-related deficits in amygdala functioning may extend across all emotions and highlight the need for further research on amygdala connectivity during emotion processing in relation to AB and CU traits within community populations.

Status epilepticus (SE) is a potentially serious condition that can affect vital and functional prognosis and requires urgent treatment. Etiology is a determining factor in the patient's functional outcome and in almost half of all cases justifies specific treatment to stop progression. Therefore, identifying and addressing the cause of SE is a key priority in SE management. However, the etiology can be difficult to identify among acute and remote causes, which can also be multiple and interrelated. The most common etiologies are the discontinuation of antiepileptic medication in patients with a prior history of epilepsy, and acute brain aggression in cases of new onset SE (cerebrovascular pathologies are the most common). The list of remaining possible etiologies includes heterogeneous pathological contexts. Refractory SE and especially New-Onset Refractory Status Epilepticus (NORSE) lead to an extension of the etiological assessment in the search for encephalitis of autoimmune or infectious origin in adults and in children, as well as a genetic pathology in children in particular. This is an overview of current knowledge of SE etiologies and a pragmatic approach for carrying out an etiological assessment based on the following steps: – Which etiological orientation is identified according to the field and clinical presentation?; – Which etiologies to look for in an inaugural SE?; – Which first-line assessment should be carried out? The place of the biological, EEG and imaging assessment is discussed; – Which etiologies to look for in case of refractory SE?

School connectedness, a construct indexing supportive school relationships, has been posited to promote resilience to environmental adversity. Consistent with prominent calls in the field, we examined the protective nature of school connectedness against two dimensions of early adversity that index multiple levels of environmental exposure (violence exposure, social deprivation) when predicting both positive and negative outcomes in longitudinal data from 3,246 youth in the Fragile Families and Child Wellbeing Study (48% female, 49% African American). Child and adolescent school connectedness were promotive, even when accounting for the detrimental effects of early adversity. Additionally, childhood school connectedness had a protective but reactive association with social deprivation, but not violence exposure, when predicting externalizing symptoms and positive function. Specifically, school connectedness was protective against the negative effects of social deprivation, but the effect diminished as social deprivation became more extreme. These results suggest that social relationships at school may compensate for low levels of social support in the home and neighborhood. Our results highlight the important role that the school environment can play for youth who have been exposed to adversity in other areas of their lives and suggest specific groups that may especially benefit from interventions that boost school connectedness.

Among veterans in Veterans Health Administration (VHA) care, patients with mental health and substance use conditions experience elevated suicide rates. However, despite previously demonstrated high rates of suicidal behavior, little is known regarding suicide rates among veteran VHA users with personality disorders (PDs) as a whole, or by PD clusters (A: Eccentric; B: Dramatic; C: Fearful; and PD-not otherwise specified). PD prevalence and suicide rates were assessed through 2017; overall and by clusters for 5,517,024 veterans alive as of 12/31/2013 and with more than 2 VHA encounters in 2012-2013. In all, 46,050 (.83%) had a PD diagnosis in 2012-2013. Suicide risk was examined using proportional hazards regressions adjusted for age, sex, veteran status, clustering within a geographic region, and other mental health diagnoses. Patients with PDs had greater suicide risk than those without (156.5 vs. 46.7 per 100,000 person-years). Individuals in Cluster B, which includes borderline and antisocial PDs, were at the highest risk (178.5 per 100,000 person-years), followed by PD-not otherwise specified and Cluster C (152.6 and 121.4 per 100,000 person-years, respectively). Rates of PDs in the VHA system were lower than those usually found in community samples. Veterans with a PD diagnosis had an increased risk of suicide, which was especially elevated for those with Cluster B diagnoses. Study findings document the importance of enhancing diagnosis and treatment for veterans with PDs and targeted suicide prevention services. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) comprise a family of mucocutaneous diseases associated with significant morbidity and mortality. Previous studies have confirmed the presence of autoantibodies to desmoplakin (Dp) I and II in patients with EM, SJS, and TEN. Truncated Dp production leads to characteristic changes visible on light microscopy: perinuclear clumping of keratin filaments and dyskeratotic keratinocyte. Based on these observations, the question arises as to whether a loss of Dp immunoreactivity in skin biopsies could serve as a diagnostic marker of EM, SJS, and TEN. This study analyzed Dp immunostaining patterns in 20 patients with EM or SJS/TEN. To assess the specificity of this approach, Dp immunostaining was also performed on specimens from patients with 5 potential histologic mimics of EM, SJS, and TEN. All of the samples from patients with EM, SJS, and TEN demonstrated absent or markedly diminished staining for Dp. A χ test demonstrated a statistically significant difference between the staining patterns in EM, SJS, and TEN and each of the other diagnostic groups that were investigated. This is the first report demonstrating statistically significant specificity of Dp staining patterns in EM/SJS/TEN as compared with other interface dermatitides.

The purpose of this article is to acquaint the reader with the presentation, diagnosis, and management of Ehlers-Danlos syndrome (EDS), a group of genetic connective tissue disorders. Progressive weakness of connective tissue is the underlying cause of all types of EDS. The symptoms of EDS are numerous, with variability in presentation. However, decreased quality of life caused by chronic pain and fatigue is a commonality of all types of EDS. This article will assist the nurse practitioner in recognizing EDS and offer guidance for treatment.

Threat-related amygdala reactivity and the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis have been linked to negative psychiatric outcomes. The amygdala and HPA axis have bidirectional connections, suggesting that functional variation in one system may influence the other. However, research on the functional associations between these systems has demonstrated mixed findings, potentially due to small sample sizes and cortisol sampling and data analytic procedures that investigate only pre-post differences in cortisol rather than the specific phases of the cortisol stress response. Further, previous research has primarily utilized samples of adults of mostly European descent, limiting generalizability to those of other ethnoracial identities and ages. Therefore, studies addressing these limitations are needed in order to investigate the functional relations between amygdala reactivity to threat and HPA axis stress responsivity. Using a sample of 159 adolescents from a diverse cohort (75% African American, ages 15-17 years), the present study evaluated associations between amygdala reactivity during socioemotional processing using fMRI and HPA axis reactivity to a socially-evaluative cold pressor task. Greater amygdala activation to fearful and neutral faces was associated with greater cortisol peak values and steeper activation slope. As cortisol peak values and cortisol activation slope capture the intensity of the cortisol stress response, these data suggest that greater activation of the amygdala in response to social distress and ambiguity among adolescents may be related to hyper-reactivity of the HPA axis.

Timely care initiation is a priority within the Veterans Health Administration (VHA). Patients with serious mental illnesses (SMI) are a group that benefits from timely care initiation due to elevated risks of negative outcomes with delayed care. However, no evaluation has assessed whether VHA SMI patients disproportionately experience delays in mental health care initiation. VHA administrative care data were used to compare delays in mental health care initiation for VHA patients with and without SMI who had newly identified mental health needs. Analyses assessed rates of delayed initial mental health appointments within five settings (General Mental Health [GMH], Primary Care Mental Health Integration [PC-MHI], Post-Traumatic Stress Disorder [PTSD], Substance Use Disorder [SUD], and Psychosocial Rehabilitation clinics [PSR]). SMI patients were more likely to receive delayed initial appointments in three of five clinical settings (PTSD, SUD, PSR) and had significantly longer average wait times for an initial appointment when referred to the PTSD clinic for an initial appointment. Overall, SMI patients were equally as likely to receive delayed initial appointments. While VHA SMI patients were not more likely to experience delayed mental health care initiation overall, they were more likely to experience delays within three of the five treatment settings. Findings suggest that the majority of VHA SMI patients experience equivalent timeliness, though those with more complex needs, and particularly those with trauma-related care needs, may be more likely to experience treatment initiation delays. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The human respiratory epithelium is derived from a progenitor cell in the distal buds of the developing lung. These "bud tip progenitors" are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function in the developing human lung are poorly understood. We interrogated single-cell RNA sequencing data from multiple human lung specimens and identified a mesenchymal cell population present during development that is highly enriched for expression of the WNT agonist RSPO2, and we found that the adjacent bud tip progenitors are enriched for the RSPO2 receptor LGR5. Functional experiments using organoid models, explant cultures, and FACS-isolated RSPO2

To guide care for patients with schizophrenia, the Veterans Health Administration (VHA) evaluated the associations between current or recent use of clozapine and all-cause mortality and explored associations for other antipsychotic medications. Using a case-control design, patients with schizophrenia who died in fiscal years 2014-2018 were matched on age, sex, race, and VHA facility to up to 10 controls who were alive on the case's date of death (index date). Medication coverage during the 91 days before the index date was classified as none, partial (1-44 days), and consistent (45-91 days). Medication coverage patterns during the index period were compared to coverage patterns during the period of 92-182 days prior to index date with each medication coverage classified as no change, no coverage, increased, or decreased. Conditional logistic regression analyses controlling for patient characteristics identified no associations of consistent or increasing clozapine coverage with mortality; partial and decreasing coverage were associated with greater mortality and these effects did not differ from those of other the medications considered. Exploratory analyses considering non-clozapine antipsychotic agents suggest that consistent coverage by olanzapine may be associated with increased mortality, that mortality associated with olanzapine may be greater than aripiprazole, and that this effect can be attributed primarily to patients with diabetes. Further study of this topic is needed.

Manuscript in press at Development & Psychopathology (Submitted 8/17/2020, Accepted 11/08/2020). Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively-collected longitudinal data from the Fragile Families and Child Wellbeing Study (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala-PFC connectivity during angry face processing

Objectives: Despite substantial research linking adverse childhood experiences (ACEs) and health, it is unclear how associations differ by veteran status and military service era (draft, volunteer era). The current study evaluated differences in ACEs and health by veteran status and era, increasing understanding important for service provision as the volunteer era veteran population increases. Methods: Behavioral Risk Factor Surveillance System 2012 data were used in univariate and weighted multivariable logistic regression models to assess associations among veteran status, service era, ACEs, and health. Results: Volunteer era veterans experienced the most ACEs (M = 2.42); draft era veterans experienced the fewest (M = 1.04). Individuals reporting 3 or more ACEs were 3.67 times (95% CI = 3.22-4.19) more likely to endorse depression, 1.32 times (95% CI = 1.17-1.48) more likely to report poorer general health, and 1.77 times (95% CI = 1.58-1.97) more likely to endorse poorer physical health, compared to those reporting none. Volunteer era veterans were 2.43 times more likely to report poorer physical health (95% CI = 1.49-3.97) than draft era veterans, adjusting for ACEs. Conclusions: ACEs were associated with poorer health independent of veteran status and service era. Volunteer era veterans experienced more ACEs; need for trauma-informed services supporting whole health may increase.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Key Points Question Are violence exposure and social deprivation associated with person-specific patterns (heterogeneity) of adolescent resting-state functional connectivity? Findings In this cohort study of 175 adolescents, childhood violence exposure, but not social deprivation, was associated with reduced adolescent resting-state density of the salience and default mode networks. A data-driven algorithm, blinded to childhood adversity, identified youth with heightened violence exposure based on resting-state connectivity patterns. Meaning Childhood violence exposure appears to be associated with adolescent functional connectivity heterogeneity, which may reflect person-specific neural plasticity and should be considered in neuroscience-based interventions., Importance Adverse childhood experiences are a public health issue with negative sequelae that persist throughout life. Current theories suggest that adverse childhood experiences reflect underlying dimensions (eg, violence exposure and social deprivation) with distinct neural mechanisms; however, research findings have been inconsistent, likely owing to variability in how the environment interacts with the brain. Objective To examine whether dimensional exposure to childhood adversity is associated with person-specific patterns in adolescent resting-state functional connectivity (rsFC), defined as synchronized activity across brain regions when not engaged in a task. Design, Setting, and Participants A sparse network approach in a large sample with substantial representation of understudied, underserved African American youth was used to conduct an observational, population-based longitudinal cohort study. A total of 183 adolescents aged 15 to 17 years from Detroit, Michigan; Toledo, Ohio; and Chicago, Illinois, who participated in the Fragile Families and Child Wellbeing Study were eligible for inclusion. Environmental data from birth to adolescence were collected via telephone and in-person interviews, and neuroimaging data collected at a university lab. The study was conducted from February 1, 1998, to April 26, 2017, and data analysis was performed from January 3, 2019, to May 22, 2020. Exposures Composite variables representing violence exposure and social deprivation created from primary caregiver reports on children at ages 3, 5, and 9 years. Main Outcomes and Measures Resting-state functional connectivity person-specific network metrics (data-driven subgroup membership, density, and node degree) focused on connectivity among a priori regions of interest in 2 resting-state networks (salience network and default mode) assessed with functional magnetic resonance imaging. Results Of the 183 eligible adolescents, 175 individuals (98 girls [56%]) were included in the analysis; mean (SD) age was 15.88 (0.53) years and 127 participants (73%) were African American. Adolescents with high violence exposure were 3.06 times more likely (95% CI, 1.17-8.92) to be in a subgroup characterized by high heterogeneity (few shared connections) and low network density (sparsity). Childhood violence exposure, but not social deprivation, was associated with reduced rsFC density (β = −0.25; 95% CI, −0.41 to −0.05; P = .005), with fewer salience network connections (β = −0.26; 95% CI, −0.43 to −0.08; P = .005) and salience network-default mode connections (β = −0.20; 95% CI, −0.38 to −0.03; P = .02). Violence exposure was associated with node degree of right anterior insula (β = −0.29; 95% CI, −0.47 to −0.12; P = .001) and left inferior parietal lobule (β = −0.26; 95% CI, −0.44 to −0.09; P = .003). Conclusions and Relevance The findings of this study suggest that childhood violence exposure is associated with adolescent neural network sparsity. A community-detection algorithm, blinded to child adversity, grouped youth exposed to heightened violence based only on patterns of rsFC. The findings may have implications for understanding how dimensions of adverse childhood experiences impact individualized neural development., This cohort study examines functional connectivity in adolescents who were exposed to violence during childhood.

Childhood adversity is heterogeneous with potentially distinct dimensions of violence exposure and social deprivation. These dimensions may differentially shape emotion-based neural circuitry, such as amygdala–prefrontal cortex (PFC) white matter connectivity. Amygdala–orbitofrontal cortex (OFC) white matter connectivity has been linked to regulation of the amygdala’s response to emotional stimuli. Using a preregistered analysis plan, we prospectively examined the effects of childhood exposure to two dimensions of adversity, violence exposure and social deprivation, on the adolescent amygdala–PFC white matter connectivity. We also reproduced the negative correlation between amygdala–PFC white matter connectivity and amygdala activation to threat faces. 183 15–17-year-olds were recruited from the Fragile Families and Child Wellbeing Study — a longitudinal, birth cohort, sample of predominantly low-income youth. Probabilistic tractography revealed that childhood violence exposure and social deprivation interacted to predict the probability of adolescent right hemisphere amygdala–OFC white matter connectivity. High violence exposure with high social deprivation related to less amygdala–OFC white matter connectivity. Violence exposure was not associated with white matter connectivity when social deprivation was at mean or low levels (i.e., relatively socially supportive contexts). Therefore, social deprivation may exacerbate the effects of childhood violence exposure on the development of white matter connections involved in emotion processing and regulation. Conversely, social support may buffer against them.

COVID19 shutdowns have impacted nursing education, particularly student clinical experiences. We discuss how we adapted an accelerated MSN nursing administration clinical course to meet the needs of our practicing students and the Commission on Collegiate Nursing Education (CCNE) standards in the context of the COVID19 pandemic. Resources available through the American Organization for Nursing Leadership (AONL) were utilized. Students reported a supportive, valuable learning experience they could apply in their future practice as nurse leaders. Considerations for future revisions to the course and to the AONL Guiding Principles are also presented.

Das Spritzgussverfahren ist für die Herstellung von kostengünstigen Kunststoffbauteilen eine industrielle Schlüsseltechnologie. Die für den Prozess notwendigen Spritzgusswerkzeuge aus gehärtetem Stahl werden unter anderem durch den Prozess Mikrofräsen hergestellt, wobei es bis heute zu hohem Verschleiß an den Mikrofräswerkzeugen kommt. Begegnet werden kann dieser Herausforderung durch Spritzgusswerkzeuge, bestehend aus Nichteisenmetall-Legierungen, die eine endkonturnahe Oberflächenverstärkung durch das Aufbringen einer Wolframkarbid-Partikel-Matrix erfahren. Gegenstand dieses Beitrags ist das Mikrofräsen dieser Metal-Matrix-Composite-Beschichtung. Dabei wurde die Einsetzbarkeit des polykristallinen Diamanten ohne Bindephase als innovativem Schneidstoff untersucht und nachgewiesen. Micro-injection moulding is a key technology for the cost-effective production of plastic parts. The commonly used moulds are made of hardened steel and machined by micro-milling with coated cemented carbide tools. Today, these tools suffer from random tool breakage and excessive wear. One solution of this problem is to produce injection moulds made of non-ferrous metals and enhance them by applying a tungsten carbide matrix on the surface. Thus, this investigation addresses the micro-milling process of the resulting Metal-Matrix-Composites. Furthermore, the feasibility of binderless polycrystalline diamond as an innovative cutting material could be shown for this purpose.

In den letzten Jahren kommt es zu steigenden Inzidenzen von sexuell ubertragbaren Erkrankungen („sexually transmitted infections“, STI), die somit wieder eine grosere Rolle im urologischen Klinikalltag spielen. Welche STI sind im urologischen Alltag relevant? Welche Diagnostik und Therapie sollte hierbei angewendet werden? Der Beitrag zeigt ein Review mit evidenzbasierten Empfehlungen aus der Literatur, der aktuellen Leitlinie der European Association of Urology (EAU) und des Robert-Koch-Instituts. STI lassen sich in solche, die genitale, anale, perianale oder orale Ulzera verursachen von STI, die eine Urethritis, Zervizitis bzw. urethralen oder vaginalen Ausfluss verursachen, unterscheiden. Haufig sind jedoch asymptomatische Verlaufe. Zur Diagnostik werden uberwiegend Amplifikationsverfahren empfohlen. Bei der Therapie sollte die lokale Resistenzlage beachtet werden. Ein besonderes Augenmerk wird hierbei auf die weltweit steigende Resistenz von Gonokokken gelegt. Eine Mitbehandlung des Sexualpartners sollte unbedingt erfolgen. Zudem sollte eine Diagnose und Therapie weiterer STI aufgrund der hohen Rate an Koinfektionen erfolgen. Aufgrund der steigenden Inzidenzen von STI ist das Erkennen und evidenzbasierte Therapieren dieser Infektionen essentiell zur Vermeidung von aufsteigenden Infektionen, Spatfolgen und weiteren Ubertragungen. Vor Therapiebeginn ist eine Asservation von infektiosem Material essentiell. Die Therapie sollte initial kalkuliert (mit Rucksicht auf die lokale Resistenzlage) begonnen und nach Erhalt weiterer Erregernachweise oder des Antibiogramms ggf. adaptiert und testgerecht weitergefuhrt werden.

Bei urologischen Interventionen wird oftmals eine perioperative Antibiotikaprophylaxe zur Vermeidung von postoperativen Komplikationen verwendet. Welche Empfehlungen zur sinnvollen perioperativen Antibiotikaprophylaxe bei urologischen Interventionen zur Vermeidung von zunehmender Resistenzentwicklung und Komplikationen existieren? Der Beitrag ist ein Review mit evidenzbasierten Empfehlungen aus der Literatur und der aktuellen Leitlinie der „European Association of Urology“ (EAU). Fur urologische Interventionen existieren evidenzbasierte Empfehlungen zur Antibiotikaprophylaxe, wobei die Evidenz nicht immer ausreichend hoch ist. Bei endourologischen Eingriffen wird eine Prophylaxe mit Cephalosporinen der Gruppe 2 (oder 3), Aminopenicilline/Beta-Laktamase-Inhibitoren oder Cotrimoxazol empfohlen. Bei transrektaler Prostatastanzbiopsie werden, je nach Risiko, Fluorchinolone, Cotrimoxazol oder eine zielgerichtete Prophylaxe empfohlen. Bei laparoskopischen und offenen Prozeduren werden, teilweise optional, Cephalosporine der Gruppe 2 (oder 3), Aminopenicilline/Beta-Laktamase-Inhibitoren oder Cotrimoxazol und bei einer Zystektomie mit Eroffnung des Darms Cephalosporine der Gruppe 2 oder ein Aminopenicillin/Beta-Laktamase-Inhibitor, sowie Metronidazol empfohlen. Bei der Verwendung einer sinnvollen perioperativen Antibiotikaprophylaxe ist neben dem Berucksichtigen der personen- und operationsbezogenen Risiken auch auf das zu erwartende Erregerspektrum und die regionale Resistenzlage zu achten. Die perioperative Antibiotikaprophylaxe dient einerseits der Vermeidung von postoperativen Infektionen, andererseits spielt sie auch eine wichtige Rolle im Gesamtantibiotikaverbrauch und ist damit ein wichtiger Baustein der Antimicrobial-Stewardship-Strategien im Gesundheitswesen.

To evaluate the overall rate of adherence by general practitioners (GPs) to treatment modifications suggested at discharge from hospital and to assess the way communication between secondary and primary care could be improved. Observational prospective cohort study. Patients hospitalized from the emergency department to the acute geriatric care unit of a university hospital. 206 subjects with a mean age of 85 years. Changes in drug regimen undertaken during hospitalization were collected with the associated justifications. Adherence at one month by GPs to treatment modifications was assessed as well as modifications implemented in primary care with their rationale in case of non-adherence. Community pharmacists’ and GPs’ opinions about quality of communication and information transfer at hospital-general practice interface were investigated. 5.5 ± 2.8 drug regimen changes were done per patient during hospitalization. The rate of adherence by GPs to treatment modifications suggested at discharge from hospital was 83%. In most cases, non-adherence by GPs to treatment modifications done during hospitalization was due to dosage adjustments, symptoms resolution but also worsening of symptoms. The last of which was particularly true for psychotropic drugs. All GPs received their patients’ discharge letters but the timely dissemination still needs to be improved. Only 6.6% of community pharmacists were informed of treatment modifications done during their patients’ hospitalization. Our findings showed a successful rate of adherence by GPs to treatment modifications suggested at discharge from hospital, due to the fact that optimization was done in a collaborative way between geriatricians and hospital pharmacists and that justifications for drug regimen changes were systematically provided in discharge letters. Communication processes at the interface between secondary and primary care, particularly with community pharmacists, must be strengthened to improve seamless care.

Background Childhood adversity is, unfortunately, highly prevalent and strongly associated with later psychopathology. Recent theories posit that two dimensions of early adversity, threat and deprivation, have distinct effects on brain development. The current study evaluated whether violence exposure (threat) and social deprivation (deprivation) were associated with adolescent amygdala and ventral striatum activation, respectively, in a prospective, well-sampled, longitudinal cohort using a pre-registered, open science approach. Methods One hundred and sixty-seven adolescents from the Fragile Families and Child Wellbeing Study completed functional magnetic resonance imaging (fMRI) scanning. Prospective longitudinal data from ages 3, 5 and 9 years were used to create indices of childhood violence exposure and social deprivation. We evaluated whether these dimensions were associated with adolescent brain function in response to threatening and rewarding faces. Results Childhood violence exposure was associated with decreased amygdala habituation (i.e. more sustained activation) and activation to angry faces in adolescence, whereas childhood social deprivation was associated with decreased ventral striatum activation to happy faces in adolescence. These associations held when adjusting for the other dimension of adversity (e.g., adjusting for social deprivation when examining associations with violence exposure), the interaction of the two dimensions of adversity, gender, internalizing psychopathology, and current life stress. Conclusions Consistent with recent theories, different forms of early adversity were associated with region-specific differences in brain activation.

Deaths of despair, a composite outcome including suicide and drug- and alcohol-related deaths, have been increasing, especially in subpopulations and geographic areas sensitive to economic and social hardships. The Veterans Health Administration (VHA) has begun evaluating the utility of this concept to guide planning and evaluations of clinical and preventive services for Veterans. In this study, mortality rates for middle-aged American men for 2013 to 2017 were from CDC WONDER, and rates for all Veterans, those using VHA healthcare services (VHA-utilizers), and other (non-VHA) Veterans were derived from National Death Index data. Findings demonstrated that rates for the composite were higher in VHA-utilizers and lower in non-VHA Veterans than middle-aged American men, consistent with use of VHA services by Veterans with the greatest needs. State rates in Veteran men were significantly and positively correlated with state rates for American men, and both were correlated with other characteristics of the social environment. The lack of correlation between rates for suicide and drug-related deaths indicates that deaths of despair cannot be modeled by assuming parallel paths from reactions to community-based stressors to the component outcomes; models should allow for an impact of community characteristics on partitioning between outcomes.

The present study tested how two different dimensions of childhood adversity, violence exposure and social deprivation, were associated with the cortisol response to the Socially Evaluated Cold-Pressor task in a sample of 222 adolescents (n = 117 girls, n = 167 African American). Participants were part of the Fragile Families and Child Wellbeing Study, a probability sample of births in large US cities (>200,000) between 1998 and 2000. Our subsample includes births in three cities: Detroit, Toledo, and Chicago. The study design called for an oversampling of births to unmarried parents (3:1) which led to a large number of minority and economically disadvantaged adolescents. When children were ages 3, 5, and 9, mothers reported on exposures to violence and social deprivation that occurred in the past year. Exposures from the three waves were averaged to reflect violence exposure and social deprivation during childhood. Greater levels of violence exposure from ages 3 to 9 were associated with a blunted cortisol response to stress at age 15, even after controlling for social deprivation and other factors known to influence cortisol reactivity. Social deprivation from ages 3 to 9 was not associated with the cortisol response to stress; though in an exploratory analysis, social deprivation moderated the association between violence exposure and cortisol peak activation. In line with the Dimensional Model of Adversity and Psychopathology, these findings suggest that experiences of violence, but not social deprivation, during childhood may contribute to cortisol blunting that has been previously reported in samples with high levels of social deprivation. Findings from the present longitudinal study on a relatively large sample of under-represented minority youth provide insight into the ways two different dimensions of childhood adversity impact the cortisol response to stress.

The amygdala is critically involved in processing emotion. Through bidirectional connections, the prefrontal cortex (PFC) is hypothesized to influence amygdala reactivity. However, research that elucidates the nature of amygdala-PFC interactions - through mapping amygdala-prefrontal tracts, quantifying variability among tracts, and linking this variability to amygdala activation - is lacking. Using probabilistic tractography to map amygdala-prefrontal white matter connectivity in 142 adolescents, the present study found that white matter connectivity was greater between the amygdala and the subgenual cingulate, orbitofrontal (OFC), and dorsomedial (dmPFC) prefrontal regions than with the dorsal cingulate and dorsolateral regions. Then, using a machine-learning regression, we found that greater amygdala-PFC white matter connectivity was related to attenuated amygdala reactivity. This effect was driven by amygdala white matter connectivity with the dmPFC and OFC, supporting implicit emotion processing theories which highlight the critical role of these regions in amygdala regulation. This study is among the first to map and compare specific amygdala-prefrontal white matter tracts and to relate variability in connectivity to amygdala activation, particularly among a large sample of adolescents from a well-sampled study. By examining the association between specific amygdala-PFC tracts and amygdala activation, the present study provides novel insight into the nature of this emotion-based circuit.

Summary Introduction Faced with the increasing number of pharmaceutical products on the market, several pharmacovigilance notifications regarding confusion between look-alike and sound-alike drugs have been reported. This study of perception among patients, family physicians and pharmacists aims to evaluate drug identification factors and the risk of errors of confusion for patients. Material and methods Patients were systematically approached in randomly selected pharmacies within the Midi-Pyrenees region in France and invited to complete a questionnaire. Two other questionnaires were respectively sent to family physicians and pharmacists in the same region asking for their opinion on patients’ perception of the identification of prescribed medicines. Results Of the 768 patients interviewed, most report identifying their medications by name (brand name: 50%; generic: 21%), while a smaller number cite physical appearance (box: 16%, tablet: 7% and blister packaging: 3%). In practice the factors considered most likely to cause confusion by patients relate to drug appearance (look-alike tablets: 28%, look-alike boxes: 20% and look-alike blister packaging: 13%). In contrast, look-alike and sound-alike names (generic and brand names combined) were cited in 31% of cases. Physicians (n = 345) and pharmacists (n = 198) understimate that patients identify their treatment by name (physicians: 46%; pharmacists: 26% vs. patients: 71%), reporting instead that problems arise mainly from the appearance of medicines (physicians: identification: 52% and risk factors for confusion: 74%; pharmacists: identification: 74% and risk factors for confusion: 83%; versus patients: identification: 26%; risk factors for confusion: 61%). Discussion Our study highlights the critical role of medication name in identifying drugs among patients. However, confusion of look-alike tablets or pills figures prominently among fears surrounding medication errors. Despite several notifications of pharmacovigilance, this issue appears to be underestimated within the body of medical literature. Proper identification of medicines by patients is essential to improving medication safety and therapeutic compliance. Concrete measures can be undertaken to reach this goal.

In recent years, there has been an increasing incidence of sexually transmitted infections (STI), which in turn play a major role in urological clinical routine.Which STIs are relevant in urological clinical routine? What kind of recommendations for diagnosis and treatment exist?Review of evidence-based recommendations from the literature, current guidelines of the European Association of Urology and the Robert-Koch-Institute.STIs can be differentiated into those that cause genital, anal, perianal or oral ulcers from STIs that cause urethritis, cervicitis, or urethral or vaginal discharge. Asymptomatic courses are frequently observed. For diagnosis predominantly amplification methods are recommended. The local resistance situation should be considered. Special attention is paid to the worldwide increasing resistance of gonococci. The sexual partner should also be treated. In addition, diagnosis and therapy of other STIs should be made due to the high rate of co-infection.Due to the increasing incidence of STIs, the recognition and evidence-based treatment of these infections is essential to avoid ascending infections, long-term consequences, and further transmissions. It is important to assure the infectious material before initiating therapy to be able to switch from the initially initiated calculated therapy (also considering the local resistance situation) to a test-appropriate therapy.

En France, la Haute Autorite de sante (HAS) preconise de privilegier les prescriptions non medicamenteuses pour la prise en charge des troubles du comportement du patient dement. La consultation traditionnelle pouvant s’averer inadaptee a elle seule, la telemedecine se presente comme une solution potentielle. Nous avons realise une etude descriptive, retrospective, sur un an de teleconsultations de patients dements vivant en etablissement hebergeant des personnes âgees dependantes (EHPAD) a Toulouse, et presentant tous un ou plusieurs troubles du comportement. Nous avons decrit et compare les prescriptions medicamenteuses et non medicamenteuses avant et apres telemedecine. Notre etude concerne 16 seances (11 patients differents). Dix videoconferences (soit 62,5 %) concluent a une modification des techniques de soins, et 12 des 16 seances (soit 75 %) proposent une ou plusieurs nouvelles mesures de soins non medicamenteuses. Une prise en charge dite « optimale » selon les recommandations, qui simultanement majore les techniques de soins sans augmenter la prescription de psychotropes, a ete retrouvee lors de dix seances (soit 62,5 %). Deux seances font etat d’une application pouvant etre « partielle », en proposant des mesures non medicamenteuses tout en majorant les traitements medicamenteux. Il s’agit la d’une etude en vie reelle qui laisse entrevoir de nouvelles perspectives pour la telemedecine dans la pratique de la medecine generale.