The effect of histopathologic analysis and tissue cultures on inpatient management of cellulitis: a randomized control trial.

BACKGROUND: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis. OBJECTIVE: To determine the utility of skin biopsy and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis. DESIGN: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures. RESULTS: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2-6) vs. control: 5 IQR (3-8) days; p = 0.124). LIMITATIONS: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center. CONCLUSION: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.

Myringoplasty Using Human Birth Tissue Allografts to Repair Large Tympanic Membrane Perforations.

OBJECTIVE: Examine outcomes among a series of pediatric patients who underwent myringoplasty using human birth tissue (BT) for repair of large tympanic membrane (TM) perforations. STUDY DESIGN: Case series. SETTING: Single-institution pediatric hospital. METHODS: Retrospective chart review of patients treated with BT during a 4-year study period. Subjects who underwent myringoplasty for large (size 40% or greater) TM perforations were included for this study. Patients with a stable perforation of at least 1 month's duration preoperatively who then followed up for at least 3 months postoperatively met inclusion criteria. RESULTS: Six subjects were included in this study. One subject underwent bilateral repair; thus, this series includes a total of 7 perforations. TM perforations ranged from 40% to 70% of the TM. At initial follow-up (median of 2 months), 5 of the 7 perforations had healed. One of these 5 had evidence of a 10% recurrent perforation at 5 months, which subsequently healed. Of the 2 patients not healed at initial follow-up, 1 had only a residual pinpoint perforation that subsequently healed; the other had a persistent 30% perforation that was possibly related to their postoperative recovery period, which was complicated by a respiratory viral illness. CONCLUSION: For large TM perforations, myringoplasty with BT grafts may be a viable alternative to longer, more invasive procedures like tympanoplasty. Larger, randomized, prospective studies are needed.

Identifying and training deep learning neural networks on biomedical-related datasets.

This manuscript describes the development of a resources module that is part of a learning platform named 'NIGMS Sandbox for Cloud-based Learning' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on implementing deep learning algorithms for biomedical image data in an interactive format that uses appropriate cloud resources for data access and analyses. Biomedical-related datasets are widely used in both research and clinical settings, but the ability for professionally trained clinicians and researchers to interpret datasets becomes difficult as the size and breadth of these datasets increases. Artificial intelligence, and specifically deep learning neural networks, have recently become an important tool in novel biomedical research. However, use is limited due to their computational requirements and confusion regarding different neural network architectures. The goal of this learning module is to introduce types of deep learning neural networks and cover practices that are commonly used in biomedical research. This module is subdivided into four submodules that cover classification, augmentation, segmentation and regression. Each complementary submodule was written on the Google Cloud Platform and contains detailed code and explanations, as well as quizzes and challenges to facilitate user training. Overall, the goal of this learning module is to enable users to identify and integrate the correct type of neural network with their data while highlighting the ease-of-use of cloud computing for implementing neural networks. This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning'' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [1] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.

Optical and electronic functionality arising from controlled defect formation in nanoscale complex oxide lateral epitaxy.

Epitaxial crystallization of complex oxides provides the means to create materials with precisely selected composition, strain, and orientation, thereby controlling their functionalities. Extending this control to nanoscale three-dimensional geometries can be accomplished via a three-dimensional analog of oxide solid-phase epitaxy, lateral epitaxial crystallization. The orientation of crystals within laterally crystallized SrTiO3 systematically changes from the orientation of the SrTiO3 substrate. This evolution occurs as a function of lateral crystallization distance, with a rate of approximately 50° µm-1. The mechanism of the rotation is consistent with a steady-state stress of tens of megapascal over a 100-nanometer scale region near the moving amorphous/crystalline interface arising from the amorphous-crystalline density difference. Second harmonic generation and piezoelectric force microscopy reveal that the laterally crystallized SrTiO3 is noncentrosymmetric and develops a switchable piezoelectric response at room temperature, illustrating the potential to use lateral crystallization to control the functionality of complex oxides.

Histopathologic Features of Mucosal Head and Neck Cancer Cachexia.

Objective: Determine the histopathologic features that correlate with head and neck cancer (HNC) cachexia. Methods: A single-institution, retrospective study was performed on adults with HPV-negative, mucosal squamous cell carcinoma of the aerodigestive tract undergoing resection and free flap reconstruction from 2014 to 2019. Patients with distant metastases were excluded. Demographics, comorbidities, preoperative nutrition, and surgical pathology reports were collected. Comparisons of histopathologic features and cachexia severity were made. Results: The study included 222 predominantly male (64.9%) patients aged 61.3 ± 11.8 years. Cachexia was identified in 57.2% patients, and 18.5% were severe (≥15% weight loss). No differences in demographics were identified between the groups. Compared to control, patients with severe cachexia had lower serum hemoglobin (p=0.048) and albumin (p < 0.001), larger tumor diameter (p < 0.001), greater depth of invasion (p < 0.001), and elevated proportions of pT4 disease (p < 0.001), pN2-N3 disease (p=0.001), lymphovascular invasion (p=0.009), and extranodal extension (p=0.014). Multivariate logistic regression identified tumor size (OR [95% CI] = 1.36 [1.08-1.73]), oral cavity tumor (OR [95% CI] = 0.30 [0.11-0.84]), and nodal burden (OR [95% CI] = 1.16 [0.98-1.38]) as significant histopathologic contributors of cancer cachexia. Conclusions: Larger, more invasive tumors with nodal metastases and aggressive histologic features are associated with greater cachexia severity in mucosal HNC.

Repair of facial dog bite wound utilizing cryopreserved umbilical cord allograft.

BACKGROUND: In the United States, craniofacial injuries are the most frequently observed traumas in the pediatric population. Human birth tissue products contain growth factors, cytokines, and signaling molecules that can be potentially harnessed for tissue regeneration and wound healing. PURPOSE: A cryopreserved ultra-thick amniotic membrane (AM) allograft wound dressing was used in a patient with significant facial soft tissue loss due to a dog bite injury. METHODS: This is a single case report of a pediatric patient. After obtaining IRB exemption, operative and postoperative clinic notes were reviewed. RESULTS: A 10-year-old female presented to the emergency department after suffering a dog bite to her left cheek and upper lip, resulting in tissue loss. A cryopreserved ultra-thick AM allograft was used to cover the area of tissue loss as part of surgical reconstruction. The patient was followed up at 1 week, 3 weeks, 4 months, and 1 year after the graft was placed, and rapid healing and full epithelialization were achieved in addition to scar contracture due to wound location. CONCLUSION: In the setting of acute trauma and tissue loss, human birth tissue was found to promote epithelialization and regenerative healing of facial tissues.

A Three-Dimensional Valve-on-Chip Microphysiological System Implicates Cell Cycle Progression, Cholesterol Metabolism and Protein Homeostasis in Early Calcific Aortic Valve Disease Progression.

BACKGROUND: Calcific aortic valve disease (CAVD) is one of the most common forms of valvulopathy, with a 50% elevated risk of a fatal cardiovascular event, and greater than 15,000 annual deaths in North America alone. The treatment standard is valve replacement as early diagnostic, mitigation, and drug strategies remain underdeveloped. The development of early diagnostic and therapeutic strategies requires the fabrication of effective in vitro valve mimetic models to elucidate early CAVD mechanisms. METHODS: In this study, we developed a multilayered physiologically relevant 3D valve-on-chip (VOC) system that incorporated aortic valve mimetic extracellular matrix (ECM), porcine aortic valve interstitial cell (VIC) and endothelial cell (VEC) co-culture and dynamic mechanical stimuli. Collagen and glycosaminoglycan (GAG) based hydrogels were assembled in a bilayer to mimic healthy or diseased compositions of the native fibrosa and spongiosa. Multiphoton imaging and proteomic analysis of healthy and diseased VOCs were performed. RESULTS: Collagen-based bilayered hydrogel maintained the phenotype of the VICs. Proteins related to cellular processes like cell cycle progression, cholesterol biosynthesis, and protein homeostasis were found to be significantly altered and correlated with changes in cell metabolism in diseased VOCs. This study suggested that diseased VOCs may represent an early, adaptive disease initiation stage, which was corroborated by human aortic valve proteomic assessment. CONCLUSIONS: In this study, we developed a collagen-based bilayered hydrogel to mimic healthy or diseased compositions of the native fibrosa and spongiosa layers. When the gels were assembled in a VOC with VECs and VICs, the diseased VOCs revealed key insights about the CAVD initiation process. STATEMENT OF SIGNIFICANCE: Calcific aortic valve disease (CAVD) elevates the risk of death due to cardiovascular pathophysiology by 50%, however, prevention and mitigation strategies are lacking, clinically. Developing tools to assess early disease would significantly aid in the prevention of disease and in the development of therapeutics. Previously, studies have utilized collagen and glycosaminoglycan-based hydrogels for valve cell co-cultures, valve cell co-cultures in dynamic environments, and inorganic polymer-based multilayered hydrogels; however, these approaches have not been combined to make a physiologically relevant model for CAVD studies. We fabricated a bi-layered hydrogel that closely mimics the aortic valve and used it for valve cell co-culture in a dynamic platform to gain mechanistic insights into the CAVD initiation process using proteomic and multiphoton imaging assessment.

A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of ATP8A2-related disorders caused by missense changes.

ATPase, class 1, type 8 A, member 2 (ATP8A2) is a P4-ATPase with a critical role in phospholipid translocation across the plasma membrane. Pathogenic variants in ATP8A2 are known to cause cerebellar ataxia, impaired intellectual development, and disequilibrium syndrome 4 (CAMRQ4) which is often associated with encephalopathy, global developmental delay, and severe motor deficits. Here, we present a family with two siblings born from a consanguineous, first-cousin union from Sudan presenting with global developmental delay, intellectual disability, spasticity, ataxia, nystagmus, and thin corpus callosum. Whole exome sequencing revealed a homozygous missense variant in the nucleotide binding domain of ATP8A2 (p.Leu538Pro) that results in near complete loss of protein expression. This is in line with other missense variants in the same domain leading to protein misfolding and loss of ATPase function. In addition, by performing diffusion-weighted imaging, we identified bilateral hyperintensities in the posterior limbs of the internal capsule suggesting possible microstructural changes in axon tracts that had not been appreciated before and could contribute to the sensorimotor deficits in these individuals.

Eagle syndrome presentation and outcomes in a large surgical case series.

Objective: The purpose of this study is to describe both the common and uncommon symptoms associated with Eagle syndrome and share our experience treating a large group of patients with surgical intervention, primarily intraoral excision of the calcified stylohyoid ligament. Methods: This retrospective case series included 56 patients at least 18 years of age or older with a diagnosis of Eagle syndrome. All operations were conducted by a single surgeon at a tertiary medical center from 2015 to 2022. Charts were reviewed for demographics, prior medical/surgical history, symptoms, imaging results, operative details, and follow-up history. A phone survey inquired about presenting symptoms and symptom resolution following surgery. Results: The most common areas of pain were the ear (64.3%), underneath the angle of the mandible (50%), throat (46.4%), and neck (30.4%). Over 70% of patients reported tinnitus, dysphagia, and pain that were exacerbated by head rotation. Fifty-one of the 56 patients underwent surgical treatment, 92.2% via intraoral and 7.8% via cervical approaches. All patients (100%) reached in a phone survey stated that their symptoms resolved or improved after surgery. Conclusion: Eagle syndrome typically presents with common symptoms. However, healthcare providers must also be vigilant for less common manifestations, such as seizures or episodes of dizziness/fainting. These may be caused by calcification of the stylohyoid ligament. Intraoral surgical resection of the calcified ligament is a safe and effective treatment for most patients. Level of Evidence: Level 4.

HPLC Method for Better Separation of THC Isomers to Ensure Safety and Compliance in the Hemp Market.

The 2018 Farm Bill dictates that delta-9-tetrahydrocannabinol (Δ9-THC) concentrations must not exceed 0.3% in hemp and hemp-derived products in order to be "compliant." This narrow margin of error necessitates very precise testing methods throughout every facet of the hemp industry. Though gas chromatography has become the industry's gold standard, many hemp laboratories still use high-performance liquid chromatography (HPLC) to quantify cannabinoids, and thus there exists a need for HPLC methods that can separate delta-8-tetrahydrocannabinol (Δ8-THC) and Δ9-THC-a notoriously difficult task. This article details one such method, while simultaneously acknowledging the inevitable limits of using HPLC to separate cannabinoids. The method was also used to test Δ8-THC samples that were marketed as compliant, and it was found that all of the samples contained well over 0.3% Δ9-THC. The use of refined testing methodologies is crucial for hemp companies to ensure compliance, prevent adverse health effects, and provide consumers with accurate cannabinoid profiles of the products that they purchase.

Associations between Flood Risk and United States Census Tract-Level Health Outcomes.

Human-induced climate change has led to more frequent and severe flooding throughout the globe. We examined the association between flood risk and the prevalence of coronary heart disease, high blood pressure, asthma, and poor mental health in the UnitedStates, while taking into account different levels of social vulnerability. We aggregated flood risk variables from First Street Foundation by census tract and used principal component analysis to derive a set of five interpretable flood risk factors. The dependent variables were census-tract level disease prevalences generated by the Centers for Disease Control and Prevention. Bayesian spatial conditional autoregressive models were fit on this data to quantify the relationship between flood risk and health outcomes under different stratifications of social vulnerability. We showed that three flood risk principal components had small but significant associations with each of the health outcomes, across the different stratifications of social vulnerability. Our analysis gives the first United States-wide estimates of the associated effects of flood risk on specific health outcomes. We also show that social vulnerability is an important moderator of the relationship between flood risk and health outcomes. Our approach can be extended to other ecological studies that examine the health impacts of climate hazards.

A role for pH dynamics regulating transcription factor DNA binding selectivity.

Intracellular pH (pHi) dynamics regulates diverse cell processes such as proliferation, dysplasia, and differentiation, often mediated by the protonation state of a functionally critical histidine residue in endogenous pH sensing proteins. How pHi dynamics can directly regulate gene expression and whether transcription factors can function as pH sensors has received limited attention. We tested the prediction that transcription factors with a histidine in their DNA binding domain (DBD) that forms hydrogen bonds with nucleotides can have pH-regulated activity, which is relevant to more than 85 transcription factors in distinct families, including FOX, KLF, SOX and MITF/Myc. Focusing on FOX family transcription factors, we used unbiased SELEX-seq to identify pH-dependent DNA binding motif preferences, then confirm pH-regulated binding affinities for FOXC2, FOXM1, and FOXN1 to a canonical FkhP DNA motif that are 2.5 to 7.5 greater at pH 7.0 compared with pH 7.5. For FOXC2, we also find greater activity for an FkhP motif at lower pHi in cells and that pH-regulated binding and activity are dependent on a conserved histidine (His122) in the DBD. RNA-seq with FOXC2 also reveals pH-dependent differences in enriched promoter motifs. Our findings identify pH-regulated transcription factor-DNA binding selectivity with relevance to how pHi dynamics can regulate gene expression for myriad cell behaviours.

Descriptive Analysis of Dexmedetomidine's Utility in a Palliative Care Unit at the End of Life.

Context: Pain and symptom management at the end of life (EoL) can pose unique challenges, particularly when symptoms are refractory to conventional methods. Dexmedetomidine, originally approved for sedation in ventilated patients, has been demonstrated to be beneficial in pain management and palliative care settings by functioning as an alpha-2 agonist. Methods: A retrospective review of inpatient palliative care unit (IPU) records from January 2020 to December 2023 was conducted. Twenty-five adult patients receiving continuous dexmedetomidine for refractory pain at the EoL were identified. These patients were further evaluated for concurrent opioid, benzodiazepine, and chlorpromazine usage. Results: Patients experienced predominantly cancer-related pain, and had a median infusion duration of 5 days. Dexmedetomidine's initial dosing differed between the intensive care unit (ICU) and IPU settings. There was a trend toward a decreased opioid requirement 24 hours after initiation. Patients transferred from the ICU showed a progressive increase in opioid use. Conclusion: This study contributes to understanding dexmedetomidine's role in managing refractory symptoms at the EoL in the palliative care setting.

Pain Management for Periacetabular Osteotomy: A Systematic Review.

Background: Early post-operative pain control is essential to facilitate rapid recovery after orthopaedic surgery. Despite periacetabular osteotomy (PAO) being the gold standard treatment of prearthritic hip dysplasia, there is limited evidence assessing efficacy of early post-operative pain management strategies. Recent literature has focused on non-opioid supplemental treatments such as nerve blocks or local wound infiltration. The purpose of this systematic review was to assess efficacy of these interventions to reduce pain, facilitate mobilization, reduce length of stay after PAO surgery. Methods: A systematic review was created under the guidance of PRISMA from databases that included PubMed, OVID Medline, Embase, SCOPUS, Cochrane Central Register of Clinical Trials, and clinicaltrials.gov from their creation dates to 12/21/23. These studies were screen based on predetermined inclusion and exclusion criteria. Results: A total of six studies were included in this analysis from independent institutions. Three investigated nerve blocks (fascia iliaca, pericapsular, transversus abdominis), one investigated local wound infiltration with ropivacaine, one investigated high-dose dexamethasone, and the last investigated removal of the epidural catheter on postoperative (POD) 1 compared to POD 2. There were heterogeneous outcomes that were measured from these studies. In general, nerve blocks decreased opioid use, pain, and length of hospital stay. The local wound infiltration decreased pain on POD 3 and 4. Removing the epidural catheter on POD1 compared to POD 2 decreased pain and length of stay. High-dose dexamethasone use decreased opioid use on POD 1, otherwise, there was no difference in pain. Conclusion: In summary, supplemental pain management strategies peri-operatively for PAO surgery can decrease pain, opioid use, and length of hospital stay, though there are few studies assessing these interventions. Limiting opioid use after surgery reduces known negative consequences of the medication and facilitates rapid recovery. Clinical trials are needed that assess efficacy of supplemental pain management strategies after PAO surgery. Level of Evidence: II.

Hip Dysplasia Treated With Periacetabular Osteotomy in Patients Over 40 Years Old: A Systematic Review.

Background: Hip dysplasia is a leading cause of hip osteoarthritis. While periacetabular osteotomy (PAO) is effective for relieving pain and dysfunction caused by hip dysplasia in adolescents and young adults, there is concern that patients over 40 years of age will have an increased risk of persistent dysfunction and need for total hip arthroplasty. Current available evidence for PAO in older adults is limited and there is no systematic review in the literature focusing on this topic. The current systematic review offers insight into the demographics, patient-reported outcome measure (PROM) scores, and hip survivorship from total hip arthroplasty in patients over 40 years older treated for hip dysplasia with PAO. Methods: The review was conducted under the guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Databases that were searched included PubMed, OVID Medline, SCOPUS, Embase, Cochrane Library, and clinicaltrials.gov. Studies were screened based on predetermined inclusion and exclusion criteria. Results: Five studies were included in this systematic review. Enrollment years were 1990-2013. In total, there were 335 hips with mean ages between 43.5-47.2 years. Mean follow up was 4-10.8 years. Most patients that underwent hip preservation had Tonnis osteoarthritis grade 0-1. There was contradicting evidence whether patients >40 years did better or worse compared to <40 years; although, most patients in the >40 years group had good outcomes after PAO. PAO survivorship ranged from 67-100% depending on the study. Complications ranged from 2-36% of cases depending on the study; although, none of these complications had lasting effects. Conclusion: Patients over 40 years old appear to have positive outcomes when treated for hip dysplasia with PAO, though these patients were likely selected for no to minimal osteoarthritis, high functional status, and good health. PAO should be considered for patients with hip dysplasia over 40 years old without hip arthritis, though we recommend very selective indications. Level of Evidence: II.

Prevalence of Radiographic Hip Dysplasia in the General Adult Population: A Systematic Review.

Background: Acetabular dysplasia has a wide range of prevalence reported in the literature. This variation is likely due to differences in the population under investigation and studies focusing on cohorts with hip pain and osteoarthritis. There are reports of radiographic hip dysplasia prevalence for adults without hip pain but there is no systematic review of these studies to document the incidence in the general population. The purpose of this systematic review was to provide a full summary of all studies that report prevalence of hip dysplasia in adults without hip pain. Methods: PRISMA guidelines were utilized as an outline for this systematic review. Articles were pulled from PubMed, OVID Medline, Embase, SCOPUS, Cochrane Central Register of Clinical Trials, and clinicaltrials.gov from their inception dates to 1/7/24. Studies were included if participants were asymptomatic and reported rates of prevalence. Results: Fourteen studies were included in this systematic review. There were 10,998 hips from 5,506 participants included in this analysis. The overall prevalence of radiographic hip dysplasia was 2.3%. Eight studies of 5,930 hips reported the prevalence of hip dysplasia by sex. The prevalence rate in these studies was 3.8% in females and 2.7% in males. Conclusion: Acetabular dysplasia based on radiographic measurements is relatively common in the general adult population. Furthermore, females have a higher prevalence rate when compared to males. It is important to recognize the incidence of hip dysplasia in the asymptomatic adult population as we recommend surgical treatment for patients who present with hip pain and dysplasia. Further studies should investigate the natural history of untreated and treated hip dysplasia. Level of Evidence: III.

Motivation to Abstain from Drinking as a Moderator of Associations Between Parent and Offspring Problem Drinking.

OBJECTIVE: Motivational processes are key factors in the development and maintenance of problem drinking and include motivation to drink as well as motivation to abstain from drinking. Although motivation to drink has been widely studied, little research has considered motivation to abstain from drinking. The current study addresses this gap in research by exploring the role of motivation to abstain from drinking based on dispositional risk, fear of negative consequences, religious and family constraints, and indifference to alcohol in associations between mother and father problem drinking and the problem drinking of college students. METHOD: Data were collected from 337 U.S. college students (77.2% female, 86% White) who reported on their exposure to mother and father problem drinking, their own problem drinking, and their motivation to abstain from drinking for several reasons. RESULTS: Findings supported the protective role of motivation to abstain from drinking based on fear of negative consequences of drinking. Persons exposed to parental problem drinking who had low motivation to abstain from alcohol based on dispositional risk were vulnerable to the intergenerational transmission of problem drinking. In addition, motivation to abstain from drinking based religious or family constraints was associated with lower problem drinking regardless of exposure to parental problem drinking. CONCLUSIONS: Conviction-related motivation may be a powerful motivation to abstain from drinking, including among persons at risk due to parental problem drinking.

Predictive Factors for Intraoperative Determination for the Need of Femoral Osteochondroplasty After Periacetabular Osteotomy for Acetabular Dysplasia.

Background: Determination of need for osteochondroplasty (OCP) during periacetabular osteotomy (PAO) commonly relies on intraoperative assessment of internal rotation at 90° flexion (IRF). Performing an OCP helps decrease the risk of iatrogenic femoroacetabular impingement from PAO reduction. Avoiding impingement helps decrease risks of accelerated secondary osteoarthritis. The literature is limited for factors that predict need for OCPs during PAOs. The purpose of this study was to (1) define the characteristics of patients needing concurrent OCP and provide OCP rate based on IRF and femoral version and (2) identify predictive factors (clinical, radiographic) associated with need for OCP during PAO. As some surgeons determine need for OCP pre-operatively, predictive factors would aid decision making. Methods: This was a prospective cohort of 224 hips (207 patients) who underwent PAO for symptomatic acetabular dysplasia, of which 154 hips (69%) underwent OCP between years 2013 and 2017. Patients underwent OCP if they had restrictions in motion or impingement intra-operatively. Pre-operative factors such as age, sex, BMI, and CT findings were recorded that underwent univariate and multivariable analyses. Multivariable analysis found predictors that were described using odds ratios and 95% confidence intervals. IRF>30° and femoral version 10°-25° were used as the reference groups during categorical analysis. P-values ≤0.05 were considered significant. Results: Alpha angles >55° (OR= 2.20, CI: 1.08-4.52, p= 0.03), IRF≤20° (OR: 9.52, CI: 3.87-23.40, p<0.001), IRF >20°-30° (OR: 2.68, CI: 1.08-6.62, p=0.03), and femoral version <10° (OR: 5.26, CI: 1.09-25.30, p=0.04) were associated with increased odds of OCP. On continuous modeling, decreasing femoral version (OR: 1.07, CI: 1.02-1.12, p=0.002) and IRF (OR: 1.06, CI: 1.03-1.09, p<0.001) were associated with increased chance of OCP. For 5° changes, the chance of OCP increased by 40% (OR: 1.40, CI: 1.13-1.73, p=0.002) and 35% (OR: 1.35, IC: 1.16-1.57, p<0.001), respectively. Conclusion: Awareness of need for OCP may be valuable in peri-operative planning for these patients especially since some surgeons perform this technique arthroscopically before PAO. Factors associated with increased chances of OCP were alpha angles >55°, decreased IRF, and decreased femoral version. More studies in the future would help determine how OCP affects patient outcomes. Level of Evidence: III.

Gene-environment interactions within a precision environmental health framework.

Understanding the complex interplay of genetic and environmental factors in disease etiology and the role of gene-environment interactions (GEIs) across human development stages is important. We review the state of GEI research, including challenges in measuring environmental factors and advantages of GEI analysis in understanding disease mechanisms. We discuss the evolution of GEI studies from candidate gene-environment studies to genome-wide interaction studies (GWISs) and the role of multi-omics in mediating GEI effects. We review advancements in GEI analysis methods and the importance of large-scale datasets. We also address the translation of GEI findings into precision environmental health (PEH), showcasing real-world applications in healthcare and disease prevention. Additionally, we highlight societal considerations in GEI research, including environmental justice, the return of results to participants, and data privacy. Overall, we underscore the significance of GEI for disease prediction and prevention and advocate for integrating the exposome into PEH omics studies.

Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport.

Intraventricular hemorrhage (IVH) is a common complication of premature birth. Survivors are often left with cerebral palsy, intellectual disability, and/or hydrocephalus. Animal models suggest that brain tissue shrinkage with subsequent vascular stretch and tear is an important step in the pathophysiology, but the cause of this shrinkage is unknown. Clinical risk factors for IVH are biomarkers of hypoxic-ischemic stress, which causes mature neurons to swell. However, immature neuronal volume might shift in the opposite direction under these conditions. This is because immature neurons express the chloride salt and water transporter NKCC1, which subserves regulatory volume increases in nonneural cells, whereas mature neurons express KCC2, which subserves regulatory volume decreases. When hypoxic ischemic conditions reduce active ion transport and increase the cytoplasmic membrane permeability, the effects of these transporters will be diminished. As a consequence, while mature neurons swell (cytotoxic edema) immature neurons might shrink. After hypoxic-ischemic stress, in vivo and in vitro multi-photon imaging of perinatal transgenic mice demonstrated shrinkage of viable immature neurons, bulk tissue shrinkage, and blood vessel displacement. Neuronal shrinkage was correlated with age-dependent membrane salt and water transporter expression using immunohistochemistry. Shrinkage of immature neurons was prevented by prior genetic or pharmacological inhibition of NKCC1 transport. These findings open new avenues of investigation for the detection of acute brain injury by neuroimaging, as well as prevention of neuronal shrinkage and the ensuing IVH, in premature infants.