Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition.

We previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer's disease mouse models. Here, we designed auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. Seven days of auditory GENUS improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice. Changes in activation responses were evident in microglia, astrocytes, and vasculature. Auditory GENUS also reduced phosphorylated tau in the P301S tauopathy model. Furthermore, combined auditory and visual GENUS, but not either alone, produced microglial-clustering responses, and decreased amyloid in medial prefrontal cortex. Whole brain analysis using SHIELD revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. Thus, GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.

Probing entanglement in a 2D hard-core Bose-Hubbard lattice.

Entanglement and its propagation are central to understanding many physical properties of quantum systems1-3. Notably, within closed quantum many-body systems, entanglement is believed to yield emergent thermodynamic behaviour4-7. However, a universal understanding remains challenging owing to the non-integrability and computational intractability of most large-scale quantum systems. Quantum hardware platforms provide a means to study the formation and scaling of entanglement in interacting many-body systems8-14. Here we use a controllable 4 × 4 array of superconducting qubits to emulate a 2D hard-core Bose-Hubbard (HCBH) lattice. We generate superposition states by simultaneously driving all lattice sites and extract correlation lengths and entanglement entropy across its many-body energy spectrum. We observe volume-law entanglement scaling for states at the centre of the spectrum and a crossover to the onset of area-law scaling near its edges.

Author Correction: Impact of ionizing radiation on superconducting qubit coherence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impact of ionizing radiation on superconducting qubit coherence.

Technologies that rely on quantum bits (qubits) require long coherence times and high-fidelity operations1. Superconducting qubits are one of the leading platforms for achieving these objectives2,3. However, the coherence of superconducting qubits is affected by the breaking of Cooper pairs of electrons4-6. The experimentally observed density of the broken Cooper pairs, referred to as quasiparticles, is orders of magnitude higher than the value predicted at equilibrium by the Bardeen-Cooper-Schrieffer theory of superconductivity7-9. Previous work10-12 has shown that infrared photons considerably increase the quasiparticle density, yet even in the best-isolated systems, it remains much higher10 than expected, suggesting that another generation mechanism exists13. Here we provide evidence that ionizing radiation from environmental radioactive materials and cosmic rays contributes to this observed difference. The effect of ionizing radiation leads to an elevated quasiparticle density, which we predict would ultimately limit the coherence times of superconducting qubits of the type measured here to milliseconds. We further demonstrate that radiation shielding reduces the flux of ionizing radiation and thereby increases the energy-relaxation time. Albeit a small effect for today's qubits, reducing or mitigating the impact of ionizing radiation will be critical for realizing fault-tolerant superconducting quantum computers.

Waveguide quantum electrodynamics with superconducting artificial giant atoms.

Models of light-matter interactions in quantum electrodynamics typically invoke the dipole approximation1,2, in which atoms are treated as point-like objects when compared to the wavelength of the electromagnetic modes with which they interact. However, when the ratio between the size of the atom and the mode wavelength is increased, the dipole approximation no longer holds and the atom is referred to as a 'giant atom'2,3. So far, experimental studies with solid-state devices in the giant-atom regime have been limited to superconducting qubits that couple to short-wavelength surface acoustic waves4-10, probing the properties of the atom at only a single frequency. Here we use an alternative architecture that realizes a giant atom by coupling small atoms to a waveguide at multiple, but well separated, discrete locations. This system enables tunable atom-waveguide couplings with large on-off ratios3 and a coupling spectrum that can be engineered by the design of the device. We also demonstrate decoherence-free interactions between multiple giant atoms that are mediated by the quasi-continuous spectrum of modes in the waveguide-an effect that is not achievable using small atoms11. These features allow qubits in this architecture to switch between protected and emissive configurations in situ while retaining qubit-qubit interactions, opening up possibilities for high-fidelity quantum simulations and non-classical itinerant photon generation12,13.

De novo design of small beta barrel proteins.

Small beta barrel proteins are attractive targets for computational design because of their considerable functional diversity despite their very small size (<70 amino acids). However, there are considerable challenges to designing such structures, and there has been little success thus far. Because of the small size, the hydrophobic core stabilizing the fold is necessarily very small, and the conformational strain of barrel closure can oppose folding; also intermolecular aggregation through free beta strand edges can compete with proper monomer folding. Here, we explore the de novo design of small beta barrel topologies using both Rosetta energy-based methods and deep learning approaches to design four small beta barrel folds: Src homology 3 (SH3) and oligonucleotide/oligosaccharide-binding (OB) topologies found in nature and five and six up-and-down-stranded barrels rarely if ever seen in nature. Both approaches yielded successful designs with high thermal stability and experimentally determined structures with less than 2.4 Å rmsd from the designed models. Using deep learning for backbone generation and Rosetta for sequence design yielded higher design success rates and increased structural diversity than Rosetta alone. The ability to design a large and structurally diverse set of small beta barrel proteins greatly increases the protein shape space available for designing binders to protein targets of interest.

Yeast ribosome biogenesis factors Puf6 and Nog2 and ribosomal proteins uL2 and eL43 act in concert to facilitate the release of nascent large ribosomal subunits from the nucleolus.

Large ribosomal subunit precursors (pre-LSUs) are primarily synthesized in the nucleolus. At an undetermined step in their assembly, they are released into the nucleoplasm. Structural models of yeast pre-LSUs at various stages of assembly have been collected using cryo-EM. However, which cryo-EM model is closest to the final nucleolar intermediate of the LSU has yet to be determined. To elucidate the mechanisms of the release of pre-LSUs from the nucleolus, we assayed effects of depleting or knocking out two yeast ribosome biogenesis factors (RiBi factors), Puf6 and Nog2, and two ribosomal proteins, uL2 and eL43. These proteins function during or stabilize onto pre-LSUs between the late nucleolar stages to early nucleoplasmic stages of ribosome biogenesis. By characterizing the phenotype of these four mutants, we determined that a particle that is intermediate between the cryo-EM model State NE1 and State NE2 likely represents the final nucleolar assembly intermediate of the LSU. We conclude that the release of the RiBi factors Nip7, Nop2 and Spb1 and the subsequent stabilization of rRNA domains IV and V may be key triggers for the release of pre-LSUs from the nucleolus.

Intermolecular Interactions between Cysteine and Aromatic Amino Acids with a Phenyl Moiety in the DNA-Binding Domain of Heat Shock Factor 1 Regulate Thermal Stress-Induced Trimerization.

In this study, we investigated the trimerization mechanism and structure of heat shock factor 1 (HSF1) using western blotting, tryptophan (Trp) fluorescence spectroscopy, and molecular modeling. First, we examined the DNA-binding domains of human (Homo sapiens), goldfish (Carassius auratus), and walleye pollock (Gadus chalcogrammus) HSF1s by mutating key residues (36 and 103) that are thought to directly affect trimer formation. Human, goldfish, and walleye pollock HSF1s contain cysteine at residue 36 but cysteine (C), tyrosine (Y), and phenylalanine (F), respectively, at residue 103. The optimal trimerization temperatures for the wild-type HSF1s of each species were found to be 42, 37, and 20 °C, respectively. Interestingly, a mutation experiment revealed that trimerization occurred at 42 °C when residue 103 was cysteine, at 37 °C when it was tyrosine, and at 20 °C when it was phenylalanine, regardless of the species. In addition, it was confirmed that when residue 103 of the three species was mutated to alanine, trimerization did not occur. This suggests that in addition to trimerization via disulfide bond formation between the cysteine residues in human HSF1, trimerization can also occur via the formation of a different type of bond between cysteine and aromatic ring residues such as tyrosine and phenylalanine. We also confirmed that at least one cysteine is required for the trimerization of HSF1s, regardless of its position (residue 36 or 103). Additionally, it was shown that the trimer formation temperature is related to growth and survival in fish.

INKILN is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10.

BACKGROUND: Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate vascular disease. The role of human-specific long noncoding RNAs in VSMC inflammation is poorly understood. METHODS: Bulk RNA sequencing in differentiated human VSMCs revealed a novel human-specific long noncoding RNA called inflammatory MKL1 (megakaryoblastic leukemia 1) interacting long noncoding RNA (INKILN). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation as well as human atherosclerosis and abdominal aortic aneurysm. The transcriptional regulation of INKILN was verified through luciferase reporter and chromatin immunoprecipitation assays. Loss-of-function and gain-of-function studies and multiple RNA-protein and protein-protein interaction assays were used to uncover a mechanistic role of INKILN in the VSMC proinflammatory gene program. Bacterial artificial chromosome transgenic mice were used to study INKILN expression and function in ligation injury-induced neointimal formation. RESULTS: INKILN expression is downregulated in contractile VSMCs and induced in human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB (nuclear factor kappa B) site within its proximal promoter. INKILN activates proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks interleukin-1ß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1 and the luciferase activity of an NF-κB reporter. Furthermore, INKILN knockdown enhances MKL1 ubiquitination through reduced physical interaction with the deubiquitinating enzyme USP10 (ubiquitin-specific peptidase 10). INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in bacterial artificial chromosome transgenic mice. CONCLUSIONS: These findings elucidate an important pathway of VSMC inflammation involving an INKILN/MKL1/USP10 regulatory axis. Human bacterial artificial chromosome transgenic mice offer a novel and physiologically relevant approach for investigating human-specific long noncoding RNAs under vascular disease conditions.

Out-of-pocket costs for diagnostic testing following abnormal prostate cancer screening among privately insured men.

OBJECTIVE: Prostate cancer is the most common malignancy among men and following a positive prostate-specific antigen (PSA) screening test, patients may undergo more expensive diagnostic testing. However, testing-related out-of-pocket costs (OOPCs), which may preclude patients from completing the screening process, have not been previously quantified. OOPCs for follow-up diagnostic testing (i.e., prostate biopsy and/or magnetic resonance imaging [MRI]) in patients with private insurance undergoing prostate cancer screening were estimated. METHODS: Men ages 55 to 69 years old who underwent PSA-based prostate cancer screening from 2010 to 2020 from the IBM Marketscan database were identified. The number of patients undergoing follow-up diagnostic testing within 12 months of screening was tabulated, dividing patients into three groups: (1) biopsy only, (2) MRI only, and (3) MRI + biopsy. Over the study period, patients with nonzero cost-sharing and calculated inflation-adjusted OOPCs, adding copayment, coinsurance, and deductible payments, for each group were identified. RESULTS: Among screened patients (n = 3,075,841) from 2010 through 2020, 91,850 had a second PSA test and an elevated PSA level, of which 40,329 (43.9%) underwent subsequent diagnostic testing. More than 75% of these patients experienced cost-sharing, and median OOPCs rose substantially over the study period for patients undergoing biopsy only ($79 to $214), MRI only ($81 to $490), and MRI and biopsy ($353 to $620). CONCLUSIONS: OOPCs from diagnostic testing after prostate cancer screening are common and rising. This work aligns with the recent position statement from the American Cancer Society, that payers should eliminate cost-sharing, which may undermine the screening process, for diagnostic testing following cancer screening.

pH Dependence of HSF1 trimerization is shaped by intramolecular interactions.

Heat shock factor 1 (HSF1) primarily regulates various cellular stress responses. Previous studies have shown that low pH within the physiological range directly activates HSF1 function in vitro. However, the detailed molecular mechanisms remain unclear. This study proposes a molecular mechanism based on the trimerization behavior of HSF1 at different pH values. Extensive mutagenesis of human and goldfish HSF1 revealed that the optimal pH for trimerization depended on the identity of residue 103. In particular, when residue 103 was occupied by tyrosine, a significant increase in the optimal pH was observed, regardless of the rest of the sequence. This behavior can be explained by the protonation state of the neighboring histidine residues, His101 and His110. Residue 103 plays a key role in trimerization by forming disulfide or non-covalent bonds with Cys36. If tyrosine resides at residue 103 in an acidic environment, its electrostatic interactions with positively charged histidine residues prevent effective trimerization. His101 and His110 are neutralized at a higher pH, which releases Tyr103 to interact with Cys36 and drives the effective trimerization of HSF1. This study showed that the protonation state of a histidine residue can regulate the intramolecular interactions, which consequently leads to a drastic change in the oligomerization behavior of the entire protein.

Natural History of Colorectal Polyps Undergoing Longitudinal in Vivo CT Colonography Surveillance.

Background The natural history of colorectal polyps is not well characterized due to clinical standards of care and other practical constraints limiting in vivo longitudinal surveillance. Established CT colonography (CTC) clinical screening protocols allow surveillance of small (6-9 mm) polyps. Purpose To assess the natural history of colorectal polyps followed with CTC in a clinical screening program, with histopathologic correlation for resected polyps. Materials and Methods In this retrospective study, CTC was used to longitudinally monitor small colorectal polyps in asymptomatic adult patients from April 1, 2004, to August 31, 2020. All patients underwent at least two CTC examinations. Polyp growth patterns across multiple time points were analyzed, with histopathologic context for resected polyps. Regression analysis was performed to evaluate predictors of advanced histopathology. Results In this study of 475 asymptomatic adult patients (mean age, 56.9 years ± 6.7 [SD]; 263 men), 639 unique polyps (mean initial diameter, 6.3 mm; volume, 50.2 mm3) were followed for a mean of 5.1 years ± 2.9. Of these 639 polyps, 398 (62.3%) underwent resection and histopathologic evaluation, and 41 (6.4%) proved to be histopathologically advanced (adenocarcinoma, high-grade dysplasia, or villous content), including two cancers and 38 tubulovillous adenomas. Advanced polyps showed mean volume growth of +178% per year (752% per year for adenocarcinomas) compared with +33% per year for nonadvanced polyps and -3% per year for unresected, unretrieved, or resolved polyps (P < .001). In addition, 90% of histologically advanced polyps achieved a volume of 100 mm3 and/or volume growth rate of 100% per year, compared with 29% of nonadvanced and 16% of unresected or resolved polyps (P < .001). Polyp volume-to-diameter ratio was also significantly greater for advanced polyps. For polyps observed at three or more time points, most advanced polyps demonstrated an initial slower growth interval, followed by a period of more rapid growth. Conclusion Small colorectal polyps ultimately proving to be histopathologically advanced neoplasms demonstrated substantially faster growth and attained greater overall size compared with nonadvanced polyps. Clinical trial registration no. NCT00204867 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dachman in this issue.

CT Colonography Reporting and Data System (C-RADS): Version 2023 Update.

The CT Colonography Reporting and Data System (C-RADS) has withstood the test of time and proven to be a robust classification scheme for CT colonography (CTC) findings. C-RADS version 2023 represents an update on the scheme used for colorectal and extracolonic findings at CTC. The update provides useful insights gained since the implementation of the original system in 2005. Increased experience has demonstrated confusion on how to classify the mass-like appearance of the colon consisting of soft tissue attenuation that occurs in segments with acute or chronic diverticulitis. Therefore, the update introduces a new subcategory, C2b, specifically for mass-like diverticular strictures, which are likely benign. Additionally, the update simplifies extracolonic classification by combining E1 and E2 categories into an updated extracolonic category of E1/E2 since, irrespective of whether a finding is considered a normal variant (category E1) or an otherwise clinically unimportant finding (category E2), no additional follow-up is required. This simplifies and streamlines the classification into one category, which results in the same management recommendation.

Genicular Artery Embolization, Radiofrequency Ablation, and Corticosteroid Therapy for Knee Osteoarthritis: A Cost-Effectiveness Analysis Using Randomized Clinical Trial Data.

Background: Many patients with symptomatic knee osteoarthritis (KOA) are refractory to traditional nonsurgical treatments such as intraarticular corticosteroid (CS) injection but are not yet eligible for or decline surgery. Genicular artery embolization (GAE) and radiofrequency ablation (RFA) are emerging adjunctive or alternative minimally invasive treatments. Objective: To perform a cost-effectiveness analysis (CEA) comparing CS, GAE, and RFA, for treatment of symptomatic KOA using a Markov model based on a de novo network meta-analysis (NMA) of randomized control trials. Methods: CEA was conducted to compare GAE and RFA to CS using a Markov cohort state-transition model from a U.S. Medicare payer's perspective over a 4-year time horizon. The model incorporated each treatment's success and attrition rates, costs, and utility benefit. Utility benefit values were derived at short-term (0.5-3 months) and long-term (6-12 months) posttreatment follow-up from NMA of published RCTs using an outcome of improved knee pain and/or function. Analyses were conducted at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). Sensitivity analyses were performed, including when simulating various cost setting scenarios (i.e., office vs hospital outpatient treatment). Results: RFA demonstrated larger treatment effect than GAE, more pronounced at short-term [standardized mean difference (SMD), -1.6688, 95% CI [-2.7806; -0.5571], p=.003] than long-term (SMD -0.3822, 95% CI [-1.9743; 1.2100], p=.64) follow-up. Across cost setting scenarios, incremental cost-effectiveness ratios relative to CS were $561-1563/QALY for GAE versus $76-429/QALY for RFA (not counting scenarios in which RFA was dominated by CS). GAE demonstrated higher cost-effectiveness probability compared to RFA (41.6-54.8% vs. 18.4-29.2%, respectively). GAE was more cost-effective than RFA when the GAE clinical success rate and post-GAE utility value exceeded 32.1-51.0% and 0.562-0.617, respectively, and when the GAE quarterly attrition rate was less than 8.8-17.4%. RFA was more cost-effective when baseline pre-treatment utility values exceeded 0.695-0.713. Neither GAE costs nor RFA costs were sensitive parameters. Conclusion: Across scenarios, GAE was consistently the most likely cost-effective treatment option compared to RFA and CS, although clinical success rates, attrition rates, and utility values impact its cost-effectiveness. Clinical Impact: GAE is likely to be more cost-effective than RFA or CS for treatment of symptomatic KOA.

Tackling Challenges of Long-Term Electrode Stability in Electrochemical Treatment of 1,4-Dioxane in Groundwater.

Electrochemical advanced oxidation is an appealing point-of-use groundwater treatment option for removing pollutants such as 1,4-dioxane, which is difficult to remove by using conventional separation-based techniques. This study addresses a critical challenge in employing electrochemical cells in practical groundwater treatment─electrode stability over long-term operation. This study aims to simulate realistic environmental scenarios by significantly extending the experimental time scale, testing a flow-through cell in addition to a batch reactor, and employing an electrolyte with a conductivity equivalent to that of groundwater. We first constructed a robust titanium suboxide nanotube mesh electrode that is utilized as both anode and cathode. We then implemented a pulsed electrolysis strategy in which reactive oxygen species are generated during the anodic cycle, and the electrode is regenerated during the cathodic cycle. Under optimized conditions, single-pass treatment through the cell (effective area: 2 cm2) achieved a remarkable 65-70% removal efficiency for 1,4-dioxane in the synthetic groundwater for over 100 h continuous operation at a low current density of 5 mA cm-2 and a water flux of 6 L m-2 h-1. The electrochemical cell and pulse treatment scheme developed in this study presents a critical advancement toward practical groundwater treatment technology.

Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

Cataloging health state utility estimates for Duchenne muscular dystrophy and related conditions.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic disease resulting in progressive muscle weakness, loss of ambulation, and cardiorespiratory complications. Direct estimation of health-related quality of life for patients with DMD is challenging, highlighting the need for proxy measures. This study aims to catalog and compare existing published health state utility estimates for DMD and related conditions. METHODS: Using two search strategies, relevant utilities were extracted from the Tufts Cost-Effectiveness Analysis Registry, including health states, utility estimates, and study and patient characteristics. Analysis One identified health states with comparable utility estimates to a set of published US patient population utility estimates for DMD. A minimal clinically important difference of ± 0.03 was applied to each DMD utility estimate to establish a range, and the registry was searched to identify other health states with associated utilities that fell within each range. Analysis Two used pre-defined search terms to identify health states clinically similar to DMD. Mapping was based on the degree of clinical similarity. RESULTS: Analysis One identified 4,308 unique utilities across 2,322 cost-effectiveness publications. The health states captured a wide range of acute and chronic conditions; 34% of utility records were extrapolated for US populations (n = 1,451); 1% were related to pediatric populations (n = 61). Analysis Two identified 153 utilities with health states clinically similar to DMD. The median utility estimates varied among identified health states. Health states similar to the early non-ambulatory DMD phase exhibited the greatest difference between the median estimate of the sample (0.39) and the existing estimate from published literature (0.21). CONCLUSIONS: When available estimates are limited, using novel search strategies to identify utilities of clinically similar conditions could be an approach for overcoming the information gap. However, it requires careful evaluation of the utility instruments, tariffs, and raters (proxy or self).

Protein sequence design by conformational landscape optimization.

The protein design problem is to identify an amino acid sequence that folds to a desired structure. Given Anfinsen's thermodynamic hypothesis of folding, this can be recast as finding an amino acid sequence for which the desired structure is the lowest energy state. As this calculation involves not only all possible amino acid sequences but also, all possible structures, most current approaches focus instead on the more tractable problem of finding the lowest-energy amino acid sequence for the desired structure, often checking by protein structure prediction in a second step that the desired structure is indeed the lowest-energy conformation for the designed sequence, and typically discarding a large fraction of designed sequences for which this is not the case. Here, we show that by backpropagating gradients through the transform-restrained Rosetta (trRosetta) structure prediction network from the desired structure to the input amino acid sequence, we can directly optimize over all possible amino acid sequences and all possible structures in a single calculation. We find that trRosetta calculations, which consider the full conformational landscape, can be more effective than Rosetta single-point energy estimations in predicting folding and stability of de novo designed proteins. We compare sequence design by conformational landscape optimization with the standard energy-based sequence design methodology in Rosetta and show that the former can result in energy landscapes with fewer alternative energy minima. We show further that more funneled energy landscapes can be designed by combining the strengths of the two approaches: the low-resolution trRosetta model serves to disfavor alternative states, and the high-resolution Rosetta model serves to create a deep energy minimum at the design target structure.

Medicaid Insurance Is Associated With More Complications and Emergency Department Visits but Equivalent 5-Year Secondary Surgery Rate After Primary Hip Arthroscopy.

PURPOSE: To compare 90-day complications, 30-day emergency department (ED) visits, and 5-year rate of secondary surgeries for patients with Medicaid vs commercial insurance undergoing primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and/or labral tears using a large national database. METHODS: The PearlDiver Mariner151 database was used to identify patients with International Classification of Diseases, Tenth Revision diagnosis codes for FAIS and/or labral tear who underwent primary hip arthroscopy with femoroplasty, acetabuloplasty, and/or labral repair between 2015 and 2021. Patients with Medicaid were matched 1:4 to a control group of commercially insured patients based on age, sex, body mass index, and Elixhauser Comorbidity Index. Rates of 90-day complications and 30-day ED visits were compared using multivariate regression models. Five-year rates of secondary surgeries-revision arthroscopy or total hip arthroplasty-were compared between cohorts by Kaplan-Meier analysis. RESULTS: A total of 2,033 Medicaid patients were matched with 8,056 commercially insured patients. Rates of adverse events were low; however, Medicaid patients were significantly more likely than commercially insured patients to experience any 90-day complication (2.12% vs 1.43%; odds ratio [OR], 1.2; P = .02). Medicaid patients also experienced more 30-day ED visits than commercially insured patients (8.61% vs 4.28%), and on multivariate logistic regression, insurance status was the strongest determinant of 30-day ED visits (relative to commercial, Medicaid OR, 2.02; P < .001). Despite these differences, 5-year rates of secondary surgeries were comparable between groups (6.1% vs 6.0%; P = .6). CONCLUSIONS: In this large national database study, Medicaid patients undergoing primary hip arthroscopy showed significantly greater odds of experiencing 90-day postoperative complications and 30-day ED visits compared to commercially insured patients. Nevertheless, both groups had similar survivorship rates at 5-year follow-up, similar to prior estimates irrespective of insurance. These results document encouraging secondary surgery rates in Medicaid patients.

The impact of asymptomatic human immunodeficiency virus (HIV)-positive disease status on inpatient complications following total joint arthroplasty: a propensity score-matched analysis.

PURPOSE: The number of patients with asymptomatic human immunodeficiency virus (AHIV) is increasing as the efficacy of antiretroviral therapy improves. While there is research on operative risks associated with having HIV, there is a lack of literature describing the impact of well-controlled HIV on postoperative complications. This study seeks to elucidate the impact of AHIV on postoperative outcomes after total hip (THA) and knee (TKA) arthroplasty. METHODS: The Nationwide Inpatient Sample was retrospectively reviewed for patients undergoing TKA and THA from 2005 to 2013. Subjects were subdivided into those with AHIV and those without HIV (non-HIV). Patient demographics, hospital-related parameters, and postoperative complications were all collected. One-to-one propensity score-matching, Chi-square analysis, and multivariate logistical regressions were performed to compare both cohorts. RESULTS: There were no significant differences between AHIV and non-HIV patients undergoing TKA or THA in terms of sex, age, insurance status, or total costs (all, p ≥ 0.081). AHIV patients had longer lengths of stay (4.0 days) than non-HIV patients after both TKA (3.3 days) and THA (3.1 days) (p ≤ 0.011). Both TKA groups had similar postoperative complication rates (p > 0.081). AHIV patients undergoing THA exhibited an increased rate of overall surgical complications compared non-HIV patients (0 vs. 4.5%, p = 0.043). AHIV was not associated with increased complications following both procedures. CONCLUSION: Despite lengthier hospital stays among AHIV patients, baseline AHIV was not associated with adverse outcomes following TKA and THA. This adds to the literature and warrants further research into the impact of asymptomatic, well-controlled HIV infection on postoperative outcomes following total joint arthroplasty.