Resident cardiac macrophages mediate adaptive myocardial remodeling.

Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2-) macrophages. Herein, we identified an essential role for CCR2- macrophages in the chronically failing heart. Depletion of CCR2- macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2- macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4)-dependent pathway that controlled growth factor expression. These findings establish a role for tissue-resident macrophages in adaptive cardiac remodeling and implicate mechanical sensing in cardiac macrophage activation.

Evolution of the insect Hox gene cluster: Comparative analysis across 243 species.

The Hox gene cluster is an iconic example of evolutionary conservation between divergent animal lineages, providing evidence for ancient similarities in the genetic control of embryonic development. However, there are differences between taxa in gene order, gene number and genomic organisation implying conservation is not absolute. There are also examples of radical functional change of Hox genes; for example, the ftz, zen and bcd genes in insects play roles in segmentation, extraembryonic membrane formation and body polarity, rather than specification of anteroposterior position. There have been detailed descriptions of Hox genes and Hox gene clusters in several insect species, including important model systems, but a large-scale overview has been lacking. Here we extend these studies using the publicly-available complete genome sequences of 243 insect species from 13 orders. We show that the insect Hox cluster is characterised by large intergenic distances, consistently extreme in Odonata, Orthoptera, Hemiptera and Trichoptera, and always larger between the 'posterior' Hox genes. We find duplications of ftz and zen in many species and multiple independent cluster breaks, although certain modules of neighbouring genes are rarely broken apart suggesting some organisational constraints. As more high-quality genomes are obtained, a challenge will be to relate structural genomic changes to phenotypic change across insect phylogeny.

Diversity, duplication, and genomic organization of homeobox genes in Lepidoptera.

Homeobox genes encode transcription factors with essential roles in patterning and cell fate in developing animal embryos. Many homeobox genes, including Hox and NK genes, are arranged in gene clusters, a feature likely related to transcriptional control. Sparse taxon sampling and fragmentary genome assemblies mean that little is known about the dynamics of homeobox gene evolution across Lepidoptera or about how changes in homeobox gene number and organization relate to diversity in this large order of insects. Here we analyze an extensive data set of high-quality genomes to characterize the number and organization of all homeobox genes in 123 species of Lepidoptera from 23 taxonomic families. We find most Lepidoptera have around 100 homeobox loci, including an unusual Hox gene cluster in which the lab gene is repositioned and the ro gene is next to pb A topologically associating domain spans much of the gene cluster, suggesting deep regulatory conservation of the Hox cluster arrangement in this insect order. Most Lepidoptera have four Shx genes, divergent zen-derived loci, but these loci underwent dramatic duplication in several lineages, with some moths having over 165 homeobox loci in the Hox gene cluster; this expansion is associated with local LINE element density. In contrast, the NK gene cluster content is more stable, although there are differences in organization compared with other insects, as well as major rearrangements within butterflies. Our analysis represents the first description of homeobox gene content across the order Lepidoptera, exemplifying the potential of newly generated genome assemblies for understanding genome and gene family evolution.

Structural linkage between ligand discrimination and receptor activation by type I interferons.

Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFNα2 and IFNω reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand "anchor points" interspersed among ligand-specific interactions that "tune" the relative IFN-binding affinities, in an apparent extracellular "ligand proofreading" mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns.

Evolutionary insights into sequence modifications governing chitin recognition and chitinase inactivity in YKL-40 (HC-gp39, CHI3L1).

YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity. Contrary to the common belief associating the lack of chitinase activity with amino acid substitutions in the catalytic motif, attempts to activate YKL-40 by creating two amino acid mutations in the catalytic motif (MT-YKL-40) proved ineffective. Subsequent exploration that included creating chimeras of MT-YKL-40 and CHIT1 catalytic domains (CatDs) identified key exons responsible for YKL-40 inactivation. Introducing YKL-40 exons 3, 6, or 8 into CHIT1 CatD resulted in chitinase inactivation. Conversely, incorporating CHIT1 exons 3, 6, and 8 into MT-YKL-40 led to its activation. Our recombinant proteins exhibited properly formed disulfide bonds, affirming a defined structure in active molecules. Biochemical and evolutionary analysis indicated that the reduced chitinase activity of MT-YKL-40 correlates with specific amino acids in exon 3. M61I and T69W substitutions in CHIT1 CatD diminished chitinase activity and increased chitin binding. Conversely, substituting I61 with M and W69 with T in MT-YKL-40 triggered chitinase activity while reducing the chitin-binding activity. Thus, W69 plays a crucial role in a unique subsite within YKL-40. These findings emphasize that YKL-40, though retaining the structural framework of a mammalian chitinase, has evolved to recognize chitin while surrendering chitinase activity.

Molecular parallelism in signaling function across different sexually selected ornaments in a warbler.

Extravagant ornaments are thought to signal male quality to females choosing mates, but the evidence linking ornament size to male quality is controversial, particularly in cases in which females prefer different ornaments in different populations. Here, we use whole-genome sequencing and transcriptomics to determine the genetic basis of ornament size in two populations of a widespread warbler, the common yellowthroat (Geothlypis trichas). Within a single subspecies, females in a Wisconsin population prefer males with larger black masks as mates, while females in a New York population prefer males with larger yellow bibs. Despite being produced by different pigments in different patches on the body, the size of the ornament preferred by females in each population was linked to numerous genes that function in many of the same core aspects of male quality (e.g., immunity and oxidative balance). These relationships confirm recent hypotheses linking the signaling function of ornaments to male quality. Furthermore, the parallelism in signaling function provides the flexibility for different types of ornaments to be used as signals of similar aspects of male quality. This could facilitate switches in female preference for different ornaments, a potentially important step in the early stages of divergence among populations.

Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy.

Current chemotherapy against Mycobacterium tuberculosis (Mtb), an important human pathogen, requires a multidrug regimen lasting several months. While efforts have been made to optimize therapy by exploiting drug­drug synergies, testing new drug combinations in relevant host environments remains arduous. In particular, host environments profoundly affect the bacterial metabolic state and drug efficacy, limiting the accuracy of predictions based on in vitro assays alone. In this study, we utilized conditional Mtb knockdown mutants of essential genes as an experimentally tractable surrogate for drug treatment and probe the relationship between Mtb carbon metabolism and chemical­genetic interactions (CGIs). We examined the antitubercular drugs isoniazid, rifampicin, and moxifloxacin and found that CGIs are differentially responsive to the metabolic state, defining both environment-independent and -dependent interactions. Specifically, growth on the in vivo­relevant carbon source, cholesterol, reduced rifampicin efficacy by altering mycobacterial cell surface lipid composition. We report that a variety of perturbations in cell wall synthesis pathways restore rifampicin efficacy during growth on cholesterol, and that both environment-independent and cholesterol-dependent in vitro CGIs could be leveraged to enhance bacterial clearance in the mouse infection model. Our findings present an atlas of chemical­genetic­environmental interactions that can be used to optimize drug­drug interactions, as well as provide a framework for understanding in vitro correlates of in vivo efficacy.

Opsin Gene Duplication in Lepidoptera: Retrotransposition, Sex Linkage, and Gene Expression.

Color vision in insects is determined by signaling cascades, central to which are opsin proteins, resulting in sensitivity to light at different wavelengths. In certain insect groups, lineage-specific evolution of opsin genes, in terms of copy number, shifts in expression patterns, and functional amino acid substitutions, has resulted in changes in color vision with subsequent behavioral and niche adaptations. Lepidoptera are a fascinating model to address whether evolutionary change in opsin content and sequence evolution are associated with changes in vision phenotype. Until recently, the lack of high-quality genome data representing broad sampling across the lepidopteran phylogeny has greatly limited our ability to accurately address this question. Here, we annotate opsin genes in 219 lepidopteran genomes representing 33 families, reconstruct their evolutionary history, and analyze shifts in selective pressures and expression between genes and species. We discover 44 duplication events in opsin genes across ∼300 million years of lepidopteran evolution. While many duplication events are species or family specific, we find retention of an ancient long-wavelength-sensitive (LW) opsin duplication derived by retrotransposition within the speciose superfamily Noctuoidea (in the families Nolidae, Erebidae, and Noctuidae). This conserved LW retrogene shows life stage-specific expression suggesting visual sensitivities or other sensory functions specific to the early larval stage. This study provides a comprehensive order-wide view of opsin evolution across Lepidoptera, showcasing high rates of opsin duplications and changes in expression patterns.

Improving Orthologous Signal and Model Fit in Datasets Addressing the Root of the Animal Phylogeny.

There is conflicting evidence as to whether Porifera (sponges) or Ctenophora (comb jellies) comprise the root of the animal phylogeny. Support for either a Porifera-sister or Ctenophore-sister tree has been extensively examined in the context of model selection, taxon sampling, and outgroup selection. The influence of dataset construction is comparatively understudied. We re-examine five animal phylogeny datasets that have supported either root hypothesis using an approach designed to enrich orthologous signal in phylogenomic datasets. We find that many component orthogroups in animal datasets fail to recover major lineages as monophyletic with the exception of Ctenophora, regardless of the supported root. Enriching these datasets to retain orthogroups recovering ≥3 major lineages reduces dataset size by up to 50% while retaining underlying phylogenetic information and taxon sampling. Site-heterogeneous phylogenomic analysis of these enriched datasets recovers both Porifera-sister and Ctenophora-sister positions, even with additional constraints on outgroup sampling. Two datasets which previously supported Ctenophora-sister support Porifera-sister upon enrichment. All enriched datasets display improved model fitness under posterior predictive analysis. While not conclusively rooting animals at either Porifera or Ctenophora, we do see an increase in signal for Porifera-sister and a decrease in signal for Ctenophore-sister when data are filtered for orthologous signal. Our results indicate that dataset size and construction as well as model fit influence animal root inference.

GC Content Across Insect Genomes: Phylogenetic Patterns, Causes and Consequences.

The proportions of A:T and G:C nucleotide pairs are often unequal and can vary greatly between animal species and along chromosomes. The causes and consequences of this variation are incompletely understood. The recent release of high-quality genome sequences from the Darwin Tree of Life and other large-scale genome projects provides an opportunity for GC heterogeneity to be compared across a large number of insect species. Here we analyse GC content along chromosomes, and within protein-coding genes and codons, of 150 insect species from four holometabolous orders: Coleoptera, Diptera, Hymenoptera, and Lepidoptera. We find that protein-coding sequences have higher GC content than the genome average, and that Lepidoptera generally have higher GC content than the other three insect orders examined. GC content is higher in small chromosomes in most Lepidoptera species, but this pattern is less consistent in other orders. GC content also increases towards subtelomeric regions within protein-coding genes in Diptera, Coleoptera and Lepidoptera. Two species of Diptera, Bombylius major and B. discolor, have very atypical genomes with ubiquitous increase in AT content, especially at third codon positions. Despite dramatic AT-biased codon usage, we find no evidence that this has driven divergent protein evolution. We argue that the GC landscape of Lepidoptera, Diptera and Coleoptera genomes is influenced by GC-biased gene conversion, strongest in Lepidoptera, with some outlier taxa affected drastically by counteracting processes.

Sexually selected differences in warbler plumage are related to a putative inversion on the Z chromosome.

Large structural variants in the genome, such as inversions, may play an important role in producing population structure and local adaptation to the environment through suppression of recombination. However, relatively few studies have linked inversions to phenotypic traits that are sexually selected and may play a role in reproductive isolation. Here, we found that geographic differences in the sexually selected plumage of a warbler, the common yellowthroat (Geothlypis trichas), are largely due to differences in the Z (sex) chromosome (males are ZZ), which contains at least one putative inversion spanning 40% (31/77 Mb) of its length. The inversions on the Z chromosome vary dramatically east and west of the Appalachian Mountains, which provides evidence of cryptic population structure within the range of the most widespread eastern subspecies (G. t. trichas). In an eastern (New York) and western (Wisconsin) population of this subspecies, female prefer different male ornaments; larger black facial masks are preferred in Wisconsin and larger yellow breasts are preferred in New York. The putative inversion also contains genes related to vision, which could influence mating preferences. Thus, structural variants on the Z chromosome are associated with geographic differences in male ornaments and female choice, which may provide a mechanism for maintaining different patterns of sexual selection in spite of gene flow between populations of the same subspecies.

Danicamtiv affected isometric force and cross-bridge kinetics similarly in skinned myocardial strips from male and female rats.

Myotropes are pharmaceuticals that have recently been developed or are under investigation for the treatment of heart diseases. Myotropes have had varied success in clinical trials. Initial research into myotropes have widely focused on animal models of cardiac dysfunction in comparison with normal animal cardiac physiology-primarily using males. In this study we examined the effect of danicamtiv, which is one type of myotrope within the class of myosin activators, on contractile function in permeabilized (skinned) myocardial strips from male and female Sprague-Dawley rats. We found that danicamtiv increased steady-state isometric force production at sub-maximal calcium levels, leading to greater Ca2+-sensitivity of contraction for both sexes. Danicamtiv did not affect maximal Ca2+-activated force for either sex. Sinusoidal length-perturbation analysis was used to assess viscoelastic myocardial stiffness and cross-bridge cycling kinetics. Data from these measurements did not vary with sex, and the data suggest that danicamtiv slows cross-bridge cycling kinetics. These findings imply that danicamtiv increases force production via increasing cross-bridge contributions to activation of contraction, especially at sub-maximal Ca2+-activation. The inclusion of both sexes in animal models during the formative stages of drug development could be helpful for understanding the efficacy or limitation of a drug's therapeutic impact on cardiac function.

Poly-basic peptides and polymers as new drug candidates against Plasmodium falciparum.

BACKGROUND: Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite's growing resistance to existing therapies. In this study, a common characteristic of the P. falciparum proteome-stretches of poly-lysine residues, such as those found in proteins related to adhesion and pathogenicity-is investigated for its potential to treat infected erythrocytes. METHODS: This study utilizes in vitro culturing of intra-erythrocytic P. falciparum to assess the ability of poly-lysine peptides to inhibit the parasite's growth, measured via flow cytometry of acridine orange-stained infected erythrocytes. The inhibitory effect of many poly-lysine lengths and modifications were tested this way. Affinity pull-downs and mass spectrometry were performed to identify the proteins interacting with these poly-lysines. RESULTS: A single dose of these poly-basic peptides can successfully diminish parasitemia in human erythrocytes in vitro with minimal toxicity. The effectiveness of the treatment correlates with the length of the poly-lysine peptide, with 30 lysine peptides supporting the eradication of erythrocytic parasites within 72 h. PEG-ylation of the poly-lysine peptides or utilizing poly-lysine dendrimers and polymers retains or increases parasite clearance efficiency and bolsters the stability of these potential new therapeutics. Lastly, affinity pull-downs and mass-spectrometry identify P. falciparum's outer membrane proteins as likely targets for polybasic peptide medications. CONCLUSION: Since poly-lysine dendrimers are already FDA-approved for drug delivery and this study displays their potency against intraerythrocytic P. falciparum, their adaptation as anti-malarial drugs presents a promising new therapeutic strategy for malaria.

The effects of TGF-ß1 and IFN-α2b on decorin, decorin isoforms and type I collagen in hypertrophic scar dermal fibroblasts.

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down-regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro-fibrotic transforming growth factor-beta 1 (TGF-ß1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon-alpha 2b (IFN-α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF-ß1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF-ß1 and IFN-α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF-ß1 and/or IFN-α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF-ß1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN-α2b showed the opposite effect. IFN-α2b significantly inhibited TGF-ß1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF-ß1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN-α2b is an important agent in reducing fibrotic outcomes.

Artificial Intelligence Driven Prehospital ECG Interpretation for the Reduction of False Positive Emergent Cardiac Catheterization Lab Activations: A Retrospective Cohort Study.

OBJECTIVES: Data suggest patients suffering acute coronary occlusion myocardial infarction (OMI) benefit from prompt primary percutaneous intervention (PPCI). Many emergency medical services (EMS) activate catheterization labs to reduce time to PPCI, but suffer a high burden of inappropriate activations. Artificial intelligence (AI) algorithms show promise to improve electrocardiogram (ECG) interpretation. The primary objective was to evaluate the potential of AI to reduce false positive activations without missing OMI. METHODS: Electrocardiograms were categorized by (1) STEMI criteria, (2) ECG integrated device software and (3) a proprietary AI algorithm (Queen of Hearts (QOH), Powerful Medical). If multiple ECGs were obtained and any one tracing was positive for a given method, that diagnostic method was considered positive. The primary outcome was OMI defined as an angiographic culprit lesion with either TIMI 0-2 flow; or TIMI 3 flow with either peak high sensitivity troponin-I > 5000 ng/L or new wall motion abnormality. The primary analysis was per-patient proportion of false positives. RESULTS: A total of 140 patients were screened and 117 met criteria. Of these, 48 met the primary outcome criteria of OMI. There were 80 positives by STEMI criteria, 88 by device algorithm, and 77 by AI software. All approaches reduced false positives, 27% for STEMI, 22% for device software, and 34% for AI (p < 0.01 for all). The reduction in false positives did not significantly differ between STEMI criteria and AI software (p = 0.19) but STEMI criteria missed 6 (5%) OMIs, while AI missed none (p = 0.01). CONCLUSIONS: In this single-center retrospective study, an AI-driven algorithm reduced false positive diagnoses of OMI compared to EMS clinician gestalt. Compared to AI (which missed no OMI), STEMI criteria also reduced false positives but missed 6 true OMI. External validation of these findings in prospective cohorts is indicated.

Dementia Friendly communities (DFCs) to improve quality of life for people with dementia: a realist review.

BACKGROUND: Currently, there are more than 55 million people living with dementia worldwide. Supporting people with dementia to live as independently as possible in their communities is a global public health objective. There is limited research exploring the implementation of such interventions in the community context. The aim of the review was to create and refine programme theory - in the form of context mechanism-outcome configurations - on how the characteristics of dementia-friendly communities (DFCs) as geographical locations interact with their social and organisational contexts to understand what works for whom and why. METHODS: This realist review sourced literature from 5 electronic databases: Cochrane Library, CINAHL, Medline, Scopus, PsychINFO and Google Scholar, as well as relevant websites such as Alzheimer's Society to identify grey literature. Methodological rigour was assessed using the Joanna Briggs Institute critical appraisal tool. RESULTS: Seven papers were included in this realist review that focused on DFCs in a geographical context The implementation of DFC interventions emerged as a process characterised by two pivotal implementation phases, intricately linked with sub-interventions. The first intervention, termed Hierarchy Commitment (I1a/b), involves the formalisation of agreements by businesses and organizations, along with the implementation of dementia-friendly action plans. Additionally, Educational Resources (I1c) play a significant role in this phase, engaging individuals with dementia and their caregivers in educational initiatives. The second phase, Geographical/Environmental Requirements (I2), encompasses the establishment of effective dementia-friendly signage, accessible meeting places, and community support. CONCLUSIONS: This realist review highlighted a theoretical framework that might guide the development of dementia-friendly communities to enhance the experiences of individuals with dementia and their caregivers within DFCs. Emphasising the need for a theoretical framework in developing geographical DFCs, the review outlines contextual elements, mechanisms, and outcomes, providing a foundation for future studies. The ultimate goal is to establish a robust body of evidence for the sustainable implementation of dementia-friendly communities, thereby improving the quality of life for those with dementia. STUDY REGISTRATION: This study is registered as PROSPERO 2022 CRD42022317784.

The Year in Aortic Surgery: Selected Highlights From 2023.

This article reviews the recent and relevant literature to the field of aortic surgery. Specific areas highlighted include outcomes of Stanford type A dissection, management of acute aortic syndromes, management of aortic aneurysms, and traumatic aortic injury. Although the focus was on articles from 2023, literature from prior years also was included, given that this article is the first of a series. Notably, the pertinent sections from the 2022 American College of Cardiology/American Heart Association Guidelines for the Diagnosis and Management Aortic Disease are discussed.

Paleoclimate-conditioning reveals a North Africa land-atmosphere tipping point.

While paleoclimate records show that the Earth System is characterized by several different tipping points, their representation within Earth System models (ESMs) remains poorly constrained. This is because historical observations do not encompass variations large enough to provoke such regime changes, and paleoclimate conditions are rarely used to help develop and tune ESMs, which potentially ignores a rich source of information on abrupt climate change. A critical example is the early to mid-Holocene "greening" and subsequent rapid desertification of the Sahara, which most ESMs fail to reproduce, casting doubt on the representation of land-atmosphere coupling and monsoon dynamics. Here, we show that this greening and abrupt termination can be successfully simulated with one ESM after optimizing uncertain model components using both present-day observations and crucially mid-Holocene (6,000 y before present) reconstructions. The optimized model displays abrupt threshold behavior, which shows excellent agreement with long paleoclimate records that were not used in the original optimization. These results suggest that in order to realistically capture climate-system thresholds, ESMs first need to be conditioned with appropriate paleoclimate information.

Breaking the Rules in Three Dimensions: What to Expect After a Thoracic-only Fusion With Structural Thoracic and Thoracolumbar Curves.

OBJECTIVE: Despite guidelines to fuse both thoracic and thoracolumbar/lumbar (TH/L) curves in patients with structural curves in both regions, a thoracic-only fusion allows preservation of lumbar motion segments. The purpose of this study was to assess the 2-year postoperative three-dimensional (3D) radiographic and clinical outcomes of patients with double or triple major (thoracic curves >TH/L curves) structural curves who underwent a thoracic-only fusion. METHODS: A prospective adolescent idiopathic scoliosis registry was queried for double or triple major curves undergoing thoracic-only posterior fusion and a minimum 2-year follow-up. 3D reconstructions were generated from bi-planar radiographs. Paired sample t tests were used to assess differences in the coronal, sagittal, and axial planes pre and postoperatively, as well as Scoliosis Research Society Questionnaire-22 scores. Pearson correlations were utilized to identify variables related to spontaneous lumbar derotation. RESULTS: Twenty-two patients met the inclusion criteria. Both thoracic [61 ± 10 degrees to 20 ± 9 degrees ( P < 0.001)] and lumbar curves [41 ± 7 degrees to 22±7 degrees ( P < 0.001)] had significant coronal improvement and T5 to T12 kyphosis improved from 7 ± 14 degrees to 23 ± 8 degrees ( P < 0.001). The thoracic apical translation was significantly improved postoperatively (4.7 ± 1.5 to 0.5 ± 1 cm, P < 0.001), but the lumbar apical translation was unchanged (-1.7 ± 0.6 to -1.7±0.8 cm, P = 0.94). Scoliosis Research Society Questionnaire-22 scores significantly improved by 2 years postoperative. CONCLUSIONS: Unlike the 3D correction observed in nonstructural TH/L curves after thoracic-only fusion, patients with double or triple major curves demonstrated only spontaneous coronal correction of the lumbar curve, whereas the sagittal and axial planes were not significantly improved. These radiographic parameters did not negatively affect subjective or clinical outcomes at minimum 2-year follow-up. LEVEL OF EVIDENCE: Level IV-therapeutic.

Depression Screening in Pediatric Orthopedic Surgery Clinics and Identifying Patients At-Risk.

BACKGROUND: Up to 25% of youth experience a depressive episode by 18 years of age, leading the US Preventive Services Task Force to recommend depression screening within this population. This study aimed to understand the prevalence of depression identified within pediatric orthopedic clinics compared with primary care clinics after the implementation of a screening program and present data on the prevalence of moderate-severe depression across specific pediatric orthopedic clinics, characterizing and identifying specific populations at higher risk. METHODS: A retrospective review was performed to identify all patients screened using the 2-item and 9-item versions of the Patient Health Questionnaire (PHQ-2/PHQ-9) and the Columbia-Suicide Severity Rating Scale over a 2-year period (October 2018 to January 2021) within pediatric primary care and orthopaedic clinics. Demographic and clinical characteristics were collected. Statistical analysis was performed to compare scores between orthopedic and primary care clinics, as well as between the different pediatric orthopedic subspecialties and included χ 2 test, ANOVA, and logistic regression. RESULTS: There were 32,787 unique adolescent patients screened in primary care clinics, with an additional 14,078 unique adolescent patients screened in orthopaedic clinics, leading to a 30% increase in the overall number of patients receiving depression screening. 5.2% of patients in primary care pediatric clinics screened positive for moderate-severe depression versus 2.0% in pediatric orthopaedic clinics ( P <0.001). 2.7% of primary care patients were at risk of self-harm compared with 0.8% of orthopedic patients ( P <0.001). Within orthopaedic subspecialty clinics, the spine patients were at the highest risk of moderate-severe depression (3.5%), significantly higher than both the sports (1.4%, P =0.006) and patients with acute fracture (1.3%, P <0.001). CONCLUSIONS: This study demonstrates the high incidence of patients screening positive for depression in pediatric and adolescent orthopaedic clinics. By identifying high-risk clinics and patient groups, health care systems can apply a more practical approach and appropriately deploy behavioral health specialists for timely counseling and treatment discussions. LEVEL OF EVIDENCE: Level-III.