K Blackwell

BACKGROUND: Pelvic tilt is an important sagittal parameter that varies greatly among individuals. The objective of this study was to quantify the effect of pelvic tilt on femoral head coverage and range of motion in a dysplastic population following periacetabular osteotomy. METHODS: Twenty-three dysplastic hips from 19 patients (17 female, 2 male) were included in this study. Three-dimensional models were reconstructed using pre-operative CT images, and patient-specific neutral pelvic tilt was obtained on an anteroposterior X-ray...

INTRODUCTION: Coronavirus disease 2019 (COVID-19) affects the vascular system, subjecting patients to a hypercoagulable state. This is of particular concern for the success of microvascular free flap reconstruction. This study aims to report head and neck free flap complications in patients with COVID-19 during the perioperative period. We believe these patients are more likely to experience flap complications given the hypercoagulable state. METHODS: This is a multi-institutional retrospective case series of patients infected with COVID-19 during the perioperative period for head and neck free flap reconstruction from March 2020 to January 2022...

BACKGROUND: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. METHODS: Eight-week-old male and female C57BL/6J mice received either Nγ -nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks...

BACKGROUND: Economic hardships imposed by the pandemic could have implications for children's experiences of adversity in the home, or Adverse Childhood Experiences (ACEs). OBJECTIVE: This observational cohort study examined associations between COVID-19-related hardships and distress (e.g., job loss, caregiver stress) and the cumulative number of child ACEs reported by caregivers during the pandemic (i.e., March 1, 2020-February 28, 2022). PARTICIPANTS AND SETTING: The study included children (N = 4345; median age = 6...

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers ( n = 11,483), pregnant/postpartum individuals ( n = 1,656), adolescents ( n = 1,795), and caregivers reporting on 3-12-year-olds ( n = 2,896)...

BACKGROUND: This study aimed to identify contextual factors associated with life satisfaction during the COVID-19 pandemic for adolescents with mental, emotional, behavioral, and developmental (MEBD) disabilities. METHODS: Data were collected from a sample of 1084 adolescents aged 11-21 years from April 2020 to August 2021. This cross-sectional study used a sequential machine learning workflow, consisting of random forest regression and evolutionary tree regression, to identify subgroups of adolescents in the Environmental influences on Child Health Outcomes (ECHO) consortium who demonstrated enhanced vulnerability to lower life satisfaction as described by intersecting risk factors, protective factors, and MEBD disabilities...

Each human genome has tens of thousands of rare genetic variants; however, identifying impactful rare variants remains a major challenge. We demonstrate how use of personal multi-omics can enable identification of impactful rare variants by using the Multi-Ethnic Study of Atherosclerosis, which included several hundred individuals, with whole-genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, 10 years apart. We evaluated each multi-omics phenotype's ability to separately and jointly inform functional rare variation...

Nucleic acid vaccines, including both RNA and DNA platforms, are key technologies that have considerable promise in combating both infectious disease and cancer. However, little is known about the extrinsic factors that regulate nucleic acid vaccine responses and which may determine their effectiveness. The microbiome is recognized as a significant regulator of immune development and response, whose role in regulating some traditional vaccine platforms has recently been discovered. Using germ-free and specific pathogen-free mouse models in combination with different protein, DNA, and mRNA vaccine regimens, we demonstrate that the microbiome is a significant regulator of nucleic acid vaccine immunogenicity...

BACKGROUND: We expanded the Multidimensional Assessment Profiles (MAPS) Scales developmental specification model to characterize the normal:abnormal spectrum of internalizing (anxious and depressive) behaviors in early childhood via the MAPS-Internalizing (MAPS-INT) scale. METHODS: The MAPS-INT item pool was generated based on clinical expertise and prior research. Analyses were conducted on a sub-sample of families (n = 183) from the diverse When to Worry early childhood sample...

Alcohol Use Disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to SARS-CoV-2 infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared to non-AUD cells...

People with Parkinson's Disease (PD) have multiple symptoms, such as freezing of gait (FoG), hand tremors, speech difficulties, and balance issues, in different stages of the disease. Among these symptoms, hand tremors are present across all stages of the disease. PD hand tremors have critical consequences and negatively impact the quality of PD patients' everyday lives. Researchers have proposed a variety of wearable devices to mitigate PD tremors. However, these devices require accurate tremor detection technology to work effectively while the tremor occurs...

The Perceived Stress Scale (PSS) and PROMIS Psychological Stress Experiences-Pediatric (PPSE) are two self-report instruments that have been used with adolescents to measure subjective feelings of stress. Stress is a critical construct to evaluate, as chronic stress can result in negative long-term consequences for an individual's physical and mental health. While the PSS is more commonly used in research and clinical practice, use of the PPSE is becoming more widespread. This increased usage necessitates a way to compare the measures, for example, when changing which instrument is used in practice or when combining data from the two measures in pooled analysis...

A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration...

Up to 50% of children and adolescents in the United States (U.S.) experience sleep problems. While existing research suggests that perceived stress in caregivers is associated with poorer sleep outcomes in children, research on this relationship is often limited to infant and early childhood populations; therefore, we investigated this association in school-age children and adolescents. We used cross-sectional caregiver-reported surveys and applied item response theory (IRT) followed by meta-analysis to assess the relationship between caregiver perceived stress and child sleep disturbance, and moderation of this relationship by child age and the presence of a child mental or physical health condition...

IMPORTANCE: Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic. OBJECTIVE: To examine differences in COVID-19 pandemic-related experiences in a large sociodemographically diverse sample of children and caregivers. DESIGN, SETTING, AND PARTICIPANTS: The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico...

SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8+ T cell vaccine-response magnitudes. Comparing baseline with post-vaccination TCRβ repertoires, we observed large clonotypic expansions correlated with the frequency of spike-specific T cells...

INTRODUCTION: People living with diabetes (DM) and chronic kidney disease (CKD) can have difficulty attending multiple appointments to receive DM care. We developed and studied the utility of a DM outreach program to offer in the hemodialysis (HD) unit. METHODS: We conducted a quality improvement project in a satellite HD unit in London, Ontario, Canada between August 1, 2019 and July 31, 2022. We assessed for baseline gaps in DM care among those with DM, performed root cause analysis with key stakeholders to identify critical drivers of gaps, and conceptualized a Certified DM Educator (CDE)-led outreach program to offer in the HD unit...

Transitioning between gravitational environments results in a central reinterpretation of sensory information, producing an adapted sensorimotor state suitable for motor actions and perceptions in the new environment. Critically, this central adaptation is not instantaneous, and complete adaptation may require weeks of prolonged exposure to novel environments. To mitigate risks associated with the lagging time course of adaptation (e.g., spatial orientation misperceptions, alterations in locomotor and postural control, and motion sickness), it is critical that we better understand sensorimotor states during adaptation...

Rationale: To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units. Objectives: In 2022, an ad hoc committee of the American Thoracic Society developed a project proposal and workshop to identify opportunities and barriers for scientists who do not practice medicine to develop successful careers and achieve tenure-track faculty positions in clinical departments and divisions within academic medical centers (AMCs) in the United States. Methods: This document focuses on results from a survey of adult and pediatric pulmonary, critical care, and sleep medicine division chiefs as well as a survey of workshop participants, including faculty in departmental and school leadership roles in both basic science and clinical units within U...

Estradiol, a female sex hormone and the predominant form of estrogen, has diverse effects throughout the brain including in learning and memory. Estradiol modulates several types of learning that depend on the dorsomedial striatum (DMS), a subregion of the basal ganglia involved in goal-directed learning, cued action-selection, and motor skills. A cellular basis of learning is synaptic plasticity, and the presence of extranuclear estradiol receptors ERα, ERβ, and G protein-coupled estrogen receptor (GPER) throughout the DMS suggests that estradiol may influence rapid cellular actions including those involved in plasticity...