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Children with systemic lupus erythematosus (SLE) are at increased risk of developing kidney disease, termed childhood-onset lupus nephritis (cLN). Single cell transcriptomics of dissociated kidney tissue has advanced our understanding of LN pathogenesis, but loss of spatial resolution prevents interrogation of in situ cellular interactions. Using a technical advance in spatial transcriptomics, we generated a spatially resolved, single cell resolution atlas of kidney tissue (>400,000 cells) from eight cLN patients and two controls. Annotated cells were assigned to 35 reference cell types, including major kidney subsets and infiltrating immune cells. Analysis of spatial distribution demonstrated that individual immune lineages localize to specific regions in cLN kidneys, including myeloid cells trafficking to inflamed glomeruli and B cells clustering within tubulointerstitial immune hotspots. Notably, gene expression varied as a function of tissue location, demonstrating how incorporation of spatial data can provide new insights into the immunopathogenesis of SLE. Alterations in immune phenotypes were accompanied by parallel changes in gene expression by resident kidney stromal cells. However, there was little correlation between histologic scoring of cLN disease activity and glomerular cell transcriptional signatures at the level of individual glomeruli. Finally, we identified modules of spatially-correlated gene expression with predicted roles in induction of inflammation and the development of tubulointerstitial fibrosis. In summary, single cell spatial transcriptomics allows unprecedented insights into the molecular heterogeneity of cLN, paving the way towards more targeted and personalized treatment approaches.

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The insecticide and current use pesticide chlorpyrifos (CLP) is transported via global distillation to the Arctic where it may pose a threat to this ecosystem. CLP is readily detected in Arctic environmental compartments, but current research has not studied its partitioning between water and dissolved organic matter (DOM) nor the role of photochemistry in CLP's fate in aquatic systems. Here, the partition coefficients of CLP were quantified with various types of DOM isolated from the Arctic and an International Humic Substances Society (IHSS) reference material Suwannee River natural organic matter (SRNOM). While CLP readily partitions to DOM, CLP exhibits a significantly higher binding constant with Arctic lacustrine DOM relative to fluvial DOM or SRNOM. The experimental partitioning coefficients (KDOC) were compared to a calculated value estimated using poly parameter linear free energy relationship (pp-LFER) and was found to be in good agreement with SRNOM, but none of the Arctic DOMs. We found that Arctic KDOC values decrease with increasing SUVA254, but no correlations were observed for the other DOM compositional parameters. DOM also mediates the photodegradation of CLP, with stark differences in photo-kinetics using Arctic DOM isolated over time and space. This work highlights the chemo-diversity of Arctic DOM relative to IHSS reference materials and highlights the need for in-depth characterization of DOM that transcends the current paradigm based upon terrestrial and microbial precursors.

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BACKGROUND: Electron microscopy (EM), once an important component in diagnosing pediatric diseases, has experienced a decline in its use. To assess the impact of this, pediatric pathology practices were surveyed regarding EM services. METHODS: The Society of Pediatric Pathology Practice Committee surveyed 113 society members from 74 hospitals. Settings included 36 academic tertiary, 32 free-standing children's, and 6 community hospitals. RESULTS: Over 60% maintained in-house EM services and had more than 2 pathologists interpreting EM while reporting a shortage of EM technologists. Freestanding children's hospitals had the most specimens (100-200 per year) and more diverse specimen types. Hospitals with fewer than 50 yearly specimens often used reference laboratories. Seventeen had terminated all in-house EM services. Challenges included decreasing caseloads due to alternative diagnostic methods, high operating costs, and shortages of EM technologists and EM-proficient pathologists. Kidney, liver, cilia, heart, and muscle biopsies most often required EM. Lung/bronchoalveolar lavage, tumor, skin, gastrointestinal, nerve, platelet, and autopsy samples less commonly needed EM. CONCLUSIONS: The survey revealed challenges in maintaining EM services but demonstrated its sustained value in pediatric pathology. Pediatric pathologists may need to address the centralization of services and training to preserve EM diagnostic proficiency among pathologists who perform ultrastructural interpretations.

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The balance of lifelong learning with assessment for continued certification is a challenge faced by healthcare professions. The value of single-point-in-time assessments has been questioned, and a shift to longitudinal assessments (LA) has been undertaken to assess lifelong learning over-time. This scoping review was conducted to inform healthcare certifying organizations who are considering LA as an assessment tool of competence and lifelong learning in healthcare professionals. A search of 6 databases and grey literature yielded 957 articles. After screening and removal of duplicates, 14 articles were included. Most articles were background studies informing the underpinnings of LA in the form of progress testing, pilot studies, and process of implementation. Progress testing is used in educational settings. Pilot studies reported satisfaction with LA's ease of use, online format, and provision of lifelong learning. Implementation processes reveal that key aspects of success include stakeholder participation, phased rollout, and a publicly available content outline. Initial outcomes data affirm that LA addresses knowledge gaps, and results in improved performance on maintenance of certification exams. Future research is needed to substantiate validity evidence of LA and its correlation with high-stakes exam performance when assessing lifelong learning and continued competence of healthcare professionals over time.

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BACKGROUND: The prevalence of wheeze and asthma has risen over recent decades for all age groups, especially children. These disorders can lead to decreased quality of life, missed school, urgent care and emergency department visits, hospitalizations, and increased health care costs. Environmental exposures, including pesticide exposure, are likely a contributing factor to this increased prevalence. OBJECTIVE: To evaluate the association of pesticide exposure with childhood wheeze and asthma. METHODS: We conducted a systematic review evaluating studies of pesticide exposure (measured objectively) and child respiratory outcomes. We searched PubMed, Embase (Elsevier), CINAHL (EBSCO), Scopus (Elsevier), Cochrane Database of Systematic Reviews (Wiley), and ClinicalTrials. gov from 1988 - 2021. Main search keywords included "pesticides", "insecticides", "herbicides", "respiratory", "asthma" and "wheeze". RESULTS: Out of 5767 studies, 25 met the inclusion criteria; eight evaluated prenatal pesticide exposure (n=8407), twelve evaluated postnatal exposures (n= 50,488), and five evaluated pre-and postnatal exposures (n=20,919). Main pesticides investigated were dichlorodiphenyldichloroethylene (DDE) (14 studies) followed by organophosphates (7 studies). Primary methods of outcome assessment were questionnaire-based (84%), followed by spirometry (16%), registry data, and blood measures. Studies varied in the strength of evidence relating to study design and measures. Most studies (84%) reported a positive association of exposure with adverse child respiratory health. CONCLUSION: The studies suggest an association of pesticide exposure and childhood wheeze and asthma. The varying results and methods reinforce the need for more research and standardized approaches to these studies to confirm the suggested association of pesticide exposure and childhood wheeze and asthma.

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BACKGROUND: Identifying individuals at risk for falls during inpatient stroke rehabilitation can ensure timely implementation of falls prevention strategies to minimize the negative personal and health system consequences of falls. OBJECTIVES: To compare sociodemographic and clinical characteristics of fallers and non-fallers; and evaluate the ability of the Berg Balance Scale (BBS) and Morse Falls Scale (MFS) to predict falls in an inpatient stroke rehabilitation setting. METHODS: A longitudinal study involving a secondary analysis of health record data from 818 patients with stroke admitted to an urban, rehabilitation hospital was conducted. A fall was defined as having ≥1 fall during the hospital stay. Cut-points on the BBS and MFS, alone and in combination, that optimized sensitivity and specificity for predicting falls, were identified. RESULTS: Low admission BBS score and admission to a low-intensity rehabilitation program were associated with falling (p < .05). Optimal cut-points were 29 for the BBS (sensitivity: 82.4%; specificity: 57.4%) and 30 for the MFS (sensitivity: 73.2%; specificity: 31.4%) when used alone. Cut-points of 45 (BBS) and 30 (MFS) in combination optimized sensitivity (74.1%) and specificity (42.7%). CONCLUSIONS: A BBS cut-point of 29 alone appears superior to using the MFS alone or combined with the BBS to predict falls.

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OBJECTIVES: Spindle cell neoplasms (SCN) share a single commonality of spindle-shaped cells on histopathology but are diverse in etiology. Expanding our collective knowledge of these neoplasms could further research in targeted therapies. We present a case of pediatric cutaneous SCN with a novel etiology, and the methods used to identify its origination. CASE PRESENTATION AND RESULTS: A 1.5-year-old child presented with a 7-month history of a rapidly enlarging, erythematous, non-painful scalp mass without ulceration or bleeding. The child underwent ultrasound and magnetic resonance imaging, revealing a 2.9 × 3 × 2 cm vascular mass without intracranial connections. The mass was successfully resected at surgery. Subsequent histopathologic and genetic testing indicated a SCN harboring a previously undescribed gene rearrangement between adenylate kinase 5 (AK5) and anaplastic lymphoma kinase (ALK). The patient received close clinical follow-up and at 6 months post-surgery had no recurrent disease. CONCLUSIONS: ALK rearrangements are common amongst many tumor types, but to our knowledge, AK5::ALK rearrangement has never been reported in SCN. Considering the rapid development of targeted clinical therapies, including those targeting ALK activity, this finding could be significant in the treatment of future patients with similar clinicopathologic and genetic presentation.

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BACKGROUND: Craniolacunia, also known as lückenschädel, is a congenital abnormality of the calvaria featuring well-circumscribed areas of marked thinning, interspersed with more-normal bone. It is most commonly associated with myelomeningocele and/or Chiari 2 malformation. METHODS: Records, photographs, and histologic sections were reviewed from 13 autopsy cases with craniolacunia. To investigate normal calvarial development, 23 parietal bone samples from fetuses/infants of 16-42 weeks gestation were examined. RESULTS: Parietal bone development had reproducible morphologic stages. Bone thickness increased with gestational age, while osteoblast numbers decreased. Craniolacunia was mainly seen in neonates. Five patients had Chiari 2 malformation, 1 had hydrocephalus, and 2 had other structural CNS abnormalities. One had trisomy 18. Four had no congenital abnormalities. Two sustained intrapartum skull fractures. Histologic sections were available in 5 cases. Lacunae in term infants had architecture similar to normal calvaria at 16-20 weeks. Adjacent bone had age appropriate architecture but increased osteoblast numbers. CONCLUSIONS: This is the largest autopsy series of craniolacunia and first systematic histologic analysis of craniolacunia and the developing fetal calvaria. Decreased cerebrospinal fluid pressure, due to myelomeningocele or other structural abnormality, may promote craniolacunia development. The risk of intrapartum fracture through lacunae emphasizes the continued clinical relevance of this diagnosis.

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Purpose: Prior research has found that transgender people are less likely to have access to health care and health insurance than their cisgender peers and are more likely to delay seeking care due to systemic discrimination and stigma. To this end, this study seeks to measure transgender and gender-nonconforming (TGNC) clients' primary care utilization and compare them to their cisgender peers. Methods: Demographic data and self-reported primary care utilization from 14,372 clients attending a community health center in Los Angeles, CA, from 2018 to 2020 were examined. Descriptive statistics and multivariable regression analyses were used to examine correlates of gender identity on primary care utilization metrics-Hepatitis A, Hepatitis B, and Human Papillomavirus (HPV) vaccinations and recent primary care visits. Results: Of TGNC clients, 38.0% reported being vaccinated for Hepatitis A compared to 49.2% of cisgender clients (p<0.01) and 42.6% reported being vaccinated for Hepatitis B compared to 51.6% of cisgender clients (p<0.01). TGNC clients had higher odds of engaging with the HPV vaccination series than their cisgender peers (adjusted odds ratio [aOR]=1.28, 95% confidence interval [CI] 1.03-1.59). TGNC clients had higher odds of seeing their primary care provider within the preceding 2 years (aOR=1.72, 95% CI 1.01-2.93) compared to non-TGNC clients. Conclusions: This study's results found that TGNC clients were more likely to access certain primary care services more often than their cisgender counterparts. Our results support the efficacy of such interventions, such as a health care setting designed to support the health of gender minority people, and see similar, if not greater, primary care engagement in transgender persons compared to their cisgender peers.

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GENERAL PURPOSE: To review neonatal pressure injuries (PIs), including clinical features and challenges in evaluation and staging related to the unique anatomic features of preterm neonatal skin as well as the common sites and mechanisms of injury. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Recognize the causes of PIs in preterm neonates.2. Choose the outcomes of PIs in preterm neonates.3. Distinguish the common characteristics of preterm neonates' skin.4. Summarize the challenges clinicians face when classifying the PIs of preterm neonates.

To review neonatal pressure injuries (PIs), including clinical features and challenges in evaluation and staging related to the unique anatomic features of preterm neonatal skin, as well as the common sites and mechanisms of injury. A review of the literature and discussion of clinical experiences at a large children's hospital. Specific topics include the nature and mechanism of PIs, histomorphometric features of skin development in preterm neonates and how these features inform bedside evaluation of PI, and experience-based observations of challenges in evaluating PIs in this vulnerable population. Pressure injury staging in preterm neonates presents unique challenges: (1) The National Pressure Injury Advisory Panel PI staging model is based on visual identification of depth of injury, but because of the immaturity of the preterm neonate, skin lacks many of the visual cues present in adult PIs. Specific qualitative and quantitative differences in skin development impact the macroscopic appearance of skin at different gestational ages. (2) The most common cause of PIs in this population is related to noninvasive respiratory devices, but these injuries may be extremely small and difficult to evaluate visually. The National Pressure Injury Advisory Panel staging system can be difficult to implement accurately in the neonatal population. Further study is warranted to determine whether an alternative staging system may provide more accurate and actionable information for this population.

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Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.

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BACKGROUND: This concept analysis presents a scholarly epistemological approach to defining the attributes, empirical referents, antecedents, and consequences of a knowledge maintenance approach-known as longitudinal assessment-to professional certification. AIM: The analysis reports on the efforts of the National Board of Certification and Recertification for Nurse Anesthetists to explore this educational method as an approach to meet requirements for continued professional certification. METHOD: Using the classical approach to concept analysis, the authors explore the structure and function of longitudinal assessment and define the characteristics of the concept in a way that is meaningful to the continued certification of nursing and medical professionals. CONCLUSION: This analysis establishes a link between the goal and outcome of the continued certification process, including continuing education in nursing and medical practice, and the desirable characteristics of longitudinal assessment, which include proven principles of educational psychology. Through exploring model and borderline cases, the authors seek to demonstrate that longitudinal assessment is the best approach to foster lifelong learning of continuously evolving scientific, theoretical, and clinical knowledge in support of safe care for patients.

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Facility-based directly observed therapy (DOT) has been the standard for treating people with TB since the early 1990s. As the commitment to promote a people-centred model of care for TB grows, the use of facility-based DOT has been questioned as issues of freedom, privacy, and human rights have been raised. The disruptions caused by the COVID-19 pandemic and ensuing lockdown measures have fast-tracked the need to find alternative methods to provide treatment to people with TB. In this study, we present quantitative and qualitative findings from a global community-based survey on the challenges of administering facility-based DOT during a pandemic as well as potential alternatives. Our results found that decreased access to transportation, the fear of COVID-19, stigmatization due to overlapping symptoms, and punitive measures against quarantine violations have made it difficult for persons with TB to receive treatment at facilities, particularly in low-resource settings. Potential replacements included greater focus on community-based DOT, home delivery of treatment, multi-month dispensing, and video DOT strategies. Our study highlights the need for TB programs to re-evaluate their approach to providing treatment to people with TB, and that these changes must be made in consultation with people affected by TB and TB survivors to provide a true people-centred model of care.

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OBJECTIVES: Apple's iPhone Night Shift feature purports to reduce short-wavelength light emissions and improve sleep. We aimed to investigate these claims by comparing emerging adults' sleep outcomes associated with smartphone use before bed with iPhone's Night Shift enabled to two comparison conditions (iPhone use with no Night Shift, no iPhone use). DESIGN: Participants were randomly assigned to one of three conditions specifying iPhone use during the hour preceding bedtime for seven consecutive nights: iPhone use with Night Shift enabled; iPhone use with Night Shift disabled; and no phone use. SETTING: Participants were recruited from a western undergraduate university. PARTICIPANTS: A sample of 167 emerging adults (ages 18-24; 71.3% female) with iPhones participated in the study. MEASUREMENTS: Sleep outcomes (sleep latency, duration, efficiency and wake after sleep onset) were tracked using wrist-worn accelerometers. RESULTS: There were no significant differences in sleep outcomes across the three experimental groups. Post-hoc exploratory stratified analyses revealed a significant main effect of phone condition on sleep efficiency (P = .014) and WASO (P = .013) for participants averaging more than 6.8 hours of sleep per night, with the no phone condition demonstrating the best sleep outcomes. For those averaging less than 6.8 hours of sleep, there was no effect of phone condition on sleep outcomes. CONCLUSIONS: Across our full study sample, there were no differences in sleep outcomes attributable to Night Shift. For individuals who regularly obtained adequate sleep, abstaining from screen use resulted in better quality sleep than did phone use with Night Shift enabled.

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BACKGROUND: The immature skin of preterm infants is uniquely vulnerable to pressure and chemical injury. We sought to qualitatively and quantitatively describe the histopathologic patterns of skin development in preterm infants. METHODS: Autopsy skin samples were examined for 48 liveborn preterm infants born at 18+ to 36 weeks, and control groups of term neonates and older infants/children. Quantitative variables included thickness of the stratum corneum, epidermis, and dermis. Qualitative features included stratum corneum, rete ridges, and hair follicles. RESULTS: Patterns of maturation were reproducible. Compact keratin appeared beginning at 21-22 weeks. Basketweave keratin appeared first around hair follicles, and then became more generalized from ∼28 weeks corrected gestational age (CGA) onward. Rete ridges began to appear at ∼30 weeks. Epidemal and dermal thickness increased with age. Infants who survived ≤7 days had thicker dermis than those who survived longer, even adjusted for CGA. CONCLUSIONS: Skin development in preterm infants has reproducible milestones. Significant structural changes occurring around 28-30 weeks may improve barrier function, with implications for use of topical compounds such as chlorhexidine. The findings also highlight challenges in evaluating pressure injuries in preterm infants, and postnatal changes in skin parameters.

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CASE: A 10-year-old boy experienced a pathologic diaphyseal femur fracture through a large cyst encompassing 40% of femoral length. At age 5, he had had a traumatic ipsilateral diaphyseal femur fracture, treated with flexible nailing. Biopsy at age 10 revealed a simple bone cyst with components of aneurysmal bone cyst. Curettage, antegrade nailing, and allograft resulted in successful osseous healing. CONCLUSION: Post-traumatic cysts of long bones are rare and have not been reported to cause pathologic fracture in children. This case highlights that close scrutiny of follow-up radiographs of long bone fractures may identify clinically important post-traumatic cysts.

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Chronic pain is a growing epidemic in America. Challenges in patients' access to care, and in reimbursement to Certified Registered Nurse Anesthetists (CRNAs) who provide pain services, have resulted in a voluntary subspecialty certification in nonsurgical pain management (NSPM) for CRNAs. An evaluation was conducted of perceptions of CRNAs toward the value of certification in NSPM. An invitation to complete the Perceived Value of Certification Tool (PVCT) was sent to 474 CRNAs who identified the subspecialty practice of NSPM upon application for recertification to the NBCRNA. Data were collected on 18 factors related to the perceived value of certification in the NSPM subspecialty. Exploratory factor analysis using principal components analysis with varimax rotation was conducted to assess the latent structure of the PVCT and to identify potential constructs of CRNAs' perceptions. Reliability was assessed using Cronbach α coefficients. Of 64 CRNAs who provided data, a 3-factor solution emerged that explained 72.25% of the overall variance: personal satisfaction, professional recognition, and competence, each with excellent to good reliability (F1: α = 0.95, F2: α = 0.94, F3: α = 0.88). Identification of the 3 constructs in this study will assist with future efforts of examination validation for the subspecialty of NSPM certification for CRNAs.

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OBJECTIVES: Disaccharidase (DS) activity in duodenal biopsy specimens is the gold standard for diagnosing DS deficiency. We investigated strategies to reduce the need for DS testing and whether clinical or histopathologic factors predict DS deficiency. METHODS: A retrospective chart review analyzed 1,678 DS results in children, biopsy indication(s), and duodenal histopathology. RESULTS: One or more DSs were abnormal in 42.8%. Sufficient lactase predicted sucrase, palatinase, and maltase sufficiency (negative predictive value 97.7%). Three patients had sucrase-isomaltase deficiency (0.2%). DS deficiency was more common in biopsy specimens for positive celiac serology (78.0%). Villous blunting, intraepithelial lymphocytosis, and active inflammation predicted DS deficiency; a combination of any two had an 81.4% positive predictive value. CONCLUSIONS: Utilization could be reduced by only testing cases with normal duodenal histopathology and ongoing clinical suspicion for DS deficiency after reviewing pathology. In cases with suspected celiac disease and/or mucosal injury, DS deficiency is common and likely secondary, limiting test utility.

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