Increased Deltoid and Acromial Stress with Glenoid Lateralization and Onlay Humeral Stem Constructs in Reverse Shoulder Arthroplasty.

Background: Reverse shoulder arthroplasty (RSA) designs include multiple options for glenoid component lateralization, and humeral component lateralization and distalization (inlay/onlay constructs). The influence of combined glenoid lateralization, and humeral distalization on acromial and deltoid stresses is not well understood. The purpose of this study was to evaluate changes in deltoid and acromial stresses with variations in glenoid lateralization, and with inlay versus onlay humeral components in RSA. Methods: Finite element analysis was performed using a RSA system with both inlay and onlay configurations. Variations in total glenoid lateralization from 3 to 9 mm were evaluated. Deltoid and acromial stresses were determined following virtual implantation and with 50° of external rotation. Results: Increased glenoid lateralization resulted in greater stress of the deltoid and acromion. There was a modest increase in deltoid stress with glenoid lateralization alone (7% and 7.5% with progressive lateralization from 3 to 6 mm and 6 to 9 mm, respectively), but deltoid stress increased substantially with use of an onlay construct (60% at 9 mm of glenoid lateralization). Acromial stress correspondingly increased 37% with glenoid lateralization, and up to 117% with an onlay humeral construct. Discussion: Increased lateralization of the glenoid component resulted in increased levels of deltoid and acromial stress. For a given amount of glenoid lateralization, utilization of an inlay stem decreased acromial and deltoid stresses compared to onlay constructs. These data allow surgeons to better understand the interactions of glenoid and humeral lateralization and distalization in the setting of contemporary RSA systems.Level of Evidence: Basic Science Study: Computer Modeling.

Influence of Tibial Component Design Features and Interference Fit on Implant-Bone Micromotion in Total Ankle Replacement: A Finite Element Study.

BACKGROUND: Implant survivorship in uncemented total ankle replacement (TAR) is dependent on achieving initial stability. This is because early micromotion between the implant and bone can disrupt the process of osseointegration, leading to poor long-term outcomes. Tibial implant fixation features are designed to resist micromotion, aided by bony sidewall retention and interference fit. The goal of this study was to investigate design-specific factors influencing implant-bone micromotion in TAR tibial components with interference fit. METHODS: Three implant designs with fixation features representative of current TAR tibial components (ARC, SPIKES, KEEL) were virtually inserted into models of the distal tibias of 2 patients with end-stage ankle arthritis. Tibia models were generated from deidentified patient computed tomography scans, with material properties for modeling bone behavior and compaction during press-fit. Finite element analysis (FEA) was used to simulate 2 fixation configurations: (1) no sidewalls or interference fit, and (2) sidewalls with interference fit. Load profiles representing the stance phase of gait were applied to the models, and implant-bone micromotions were computed from FEA output. RESULTS: Sidewalls and interference fit substantially influenced implant-bone micromotions across all designs studied. When sidewalls and interference fit were modeled, average micromotions were less than 11 µm, consistent across the stance phase of gait. Without sidewalls or interference fit, micromotions were largest near either heel strike or toe-off. In the absence of sidewalls and interference fit, the amount of micromotion generally aligned inversely with the size of implant fixation features; the ARC design had the largest micromotion (~540 µm average), whereas the KEEL design had the smallest micromotion (~15 µm). CONCLUSION: This study presents new insights into the effect of TAR fixation features on implant-bone micromotion. With sidewalls and interference fit, micromotion is predicted to be minimal for implants, whereas with no sidewalls and no interference fit, micromotion depended primarily on the implant design. CLINICAL RELEVANCE: This study presents new insights into the effect of TAR primary fixation features on implant-bone micromotion. Although design features heavily influenced implant stability in the model, their influence was greatly diminished when interference fit was introduced. The results of this study show the relative importance of design features and interference fit in the predicted initial stability of uncemented TAR, potentially a key factor in implant survivorship.

Time-on-task-related decrements in performance in the rodent continuous performance test are not caused by physical disengagement from the task.

Attention deficits, a hallmark of many neuropsychiatric disorders, significantly impair quality of life and functional outcome for patients. Continuous Performance Tests (CPTs) are widely used to assess attentional function in clinical settings and have been adapted for mice as the rodent Continuous Performance Test (rCPT). In this study, we combined traditional analyses of rCPT performance with markerless pose estimation using DeepLabCut and visual field analysis (VFA) to objectively measure the orientation of mice toward stimuli during rCPT sessions. Additionally, we extended session lengths to assess performance decrements over time. Our findings show that extending rCPT sessions from 45 to 90 minutes results in a significant decline in performance in male mice, which aligns with performance decrements observed in clinical research. Importantly, physical engagement with the task remained relatively stable throughout the session, even as performance deteriorated. This suggests that the performance decline specifically reflects a time-on-task (TOT)-dependent vigilance decrement rather than physical disengagement. We also investigated the effects of amphetamine, an FDA-approved treatment for attention-deficit/hyperactivity disorder (ADHD), on rCPT performance. Amphetamine significantly improved rCPT performance in male mice by reducing false alarms without modulating orientation or physical engagement with the task stimuli. Collectively, these findings validate a behavioral tracking platform for objectively measuring physical engagement in the rCPT and a task modification that accentuates TOT-dependent performance decrements, enhancing the translational value of the rCPT for studies related to human neuropsychiatric disorders.

Skilled Nursing and Home Health Policy: A Primer for the Hospital Clinician.

This paper addresses the increasing challenges faced by hospital clinicians in coordinating and recommending postacute care for patients, focusing on issues related to access to the most common postacute services: skilled nursing facilities (SNFs) and home health agencies (HHAs). In coordinating discharges, hospital clinicians have minimal information on care delivery in these settings. This knowledge gap is exacerbated by the disrupted continuum of patient care between acute care hospitals, SNFs, and HHAs. To address these challenges, hospital clinicians must understand how recent federal policies have impacted SNF and HHA care provision. The paper provides an overview of recent Centers for Medicare and Medicaid Services (CMS) policies and programs affecting SNFs and HHAs, including: (1) fee-for-service reimbursement reform (ie, Patient Driven Payment Model [PDPM] and the Patient Driven Groupings Model [PDGM]); (2) bundled payment programs; (3) accountable care organizations; (4) Medicare Advantage plans. Overall, this paper aims to help hospital clinicians stay informed about the evolving landscape of postacute care delivery by providing relevant information on how recent policy changes have impacted patient care.

Prognostic significance of non-coding RNAs related to the tumorigenic epithelial-mesenchymal transition (EMT) process among ovarian cancer patients: A systematic review and meta-analysis.

Introduction: Ovarian cancer is the seventh most prevalent cancer among women. It has high mortality and morbidity and imposes a great burden on healthcare systems worldwide. Unraveling the mechanisms behind the Epithelial-Mesenchymal Transition and finding a panel for predicting the prognosis of the disease may help find the appropriate treatment approaches for the management of the disease. The overarching aim of this systematic review was to define a panel of different types of EMT-associated non-coding RNAs (ncRNAs) with significant prognostic value in all types of ovarian cancers. Methods: We searched PubMed, Web of Science, Scopus, and Embase till Jun 2024 to retrieve relevant papers. Two independent reviewers screened papers, and discrepancies were resolved by consensus. Publications related to the dysregulation of different types of ncRNAs, including microRNAs, lncRNAs, and circRNAs, only in patients with ovarian cancer were included. The participation of ncRNAs in epithelial-mesenchymal transformation should be assessed via methods evaluating different EMT-related proteins. To assess the quality and risk of bias for the included case-control and cohort studies, refined Newcastle-Ottawa Scale (NOS) and Quadas-2 were recruited. A bivariate meta-analysis was performed to analyze extracted data. Results: A total of 37 studies with overall 42 non-coding RNAs (15 microRNA, 24 long non-coding RNAs, and 3 circular RNAs) were entered into the analysis. Overall diagnostic odds ratio for ncRNAs in lymph node metastasis, distant metastasis, TNM stage, and clinical stage were 4.19, 3.80, 6.52, and 3.97, respectively. Also, a hazard ratio of 1.39 (P = 0.32) for overall survival was observed. Bioinformatic analyses on the Pan-cancer database demonstrated a significant correlation between low expression of miRNA and high expression of lncRNAs with poor prognosis of ovarian cancer. Conclusion: Based on the results, the defined panel of ncRNAs can properly predict prognostic factors related to EMT in ovarian cancer without involving potentially invasive methods.

Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates.

In 2022, mpox virus (MPXV) spread worldwide, causing 99,581 mpox cases in 121 countries. Modified vaccinia Ankara (MVA) vaccine use reduced disease in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central Africa of clade I virus. These outbreaks highlight the threat of zoonotic spillover by Orthopoxviruses. mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine expressing MPXV surface proteins, was tested in a lethal MPXV primate model. Similar to MVA, mRNA-1769 conferred protection against challenge and further mitigated symptoms and disease duration. Antibody profiling revealed a collaborative role between neutralizing and Fc-functional extracellular virion (EV)-specific antibodies in viral restriction and ospinophagocytic and cytotoxic antibody functions in protection against lesions. mRNA-1769 enhanced viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.

Implications of using simplified finite element meshes to identify material parameters of articular cartilage.

The objective of this work was to determine the effects of using simplified finite element (FE) mesh geometry in the process of performing reverse iterative fitting to estimate cartilage material parameters from in situ indentation testing. Six bovine tibial osteochondral explants were indented with sequential 5 % step-strains followed by a 600 s hold while relaxation force was measured. Three sets of porous viscohyperelastic material parameters were estimated for each specimen using reverse iterative fitting of the indentation test with (1) 2D axisymmetric, (2) 3D idealized, and (3) 3D specimen-specific FE meshes. Variable material parameters were identified using the three different meshes, and there were no systematic differences, correlation to basic geometric features, nor distinct patterns of variation based on the type of mesh used. Implementing the three material parameter sets in a separate 3D FE model of 40 % compressive strain produced differences in von Mises stresses and pore pressures up to 25 % and 50 %, respectively. Accurate material parameters are crucial in any FE model, and parameter differences influenced by idealized assumptions in initial material property determination have the potential to alter subsequent FE models in unpredictable ways and hinder the interpretation of their results.

Prospective solutions to ovarian reserve damage during the ovarian tissue cryopreservation and transplantation procedure.

Birth rates continue to decline as more women experience fertility issues. Assisted reproductive technologies are available for patients seeking fertility treatment, including cryopreservation techniques. Cryopreservation can be performed on gametes, embryos, or gonadal tissue and can be used for patients who desire to delay in vitro fertilization treatment. This review focuses on ovarian tissue cryopreservation, the freezing of ovarian cortex containing immature follicles. Ovarian tissue cryopreservation is the only available treatment for the restoration of ovarian function in patients who undergo gonadotoxic treatments, and its wide adoption has led to its recent designation as "no longer experimental" by the American Society for Reproductive Medicine. Ovarian tissue cryopreservation and subsequent transplantation can restore native endocrine function and can support the possibility of pregnancy and live birth for the patient. Importantly, there are multiple steps in the procedure that put the ovarian reserve at risk of damage. The graft is highly susceptible to ischemic reperfusion injury and mass primordial follicle growth activation, resulting in a "burnout" phenomenon. In this review, we summarize current efforts to combat the loss of primordial follicles in grafts through improvements in freeze and thaw protocols, transplantation techniques, and pharmacologic adjuvant treatments. We conducted a review of the literature, with emphasis on emergent research in the last 5 years. Regarding freeze and thaw protocols, we discuss the widely accepted slow freezing approach and newer vitrification protocols. Discussion of improved transplantation techniques includes consideration of the transplantation location of the ovarian tissue and the importance of graft sites in promoting neovascularization. Finally, we discuss pharmacologic treatments being studied to improve tissue performance postgraft. Of note, there is significant research into the efficacy of adjuvants used to reduce ischemic injury, improve neovascularization, and inhibit hyperactivation of primordial follicle growth activations. Although the "experimental" label has been removed from ovarian tissue cryopreservation and subsequent transplantation, there is a significant need for further research to better understand sources of ovarian reserve damage to improve outcomes. Future research directions are provided as we consider how to reach the most hopeful results for women globally.

Early physical rehabilitation dosage in the intensive care unit associates with hospital outcomes after critical COVID-19.

OBJECTIVE: To examine the relationship between physical rehabilitation parameters including an approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. DESIGN: Retrospective practice analysis from March 5, 2020, to April 15, 2021. SETTING: Intensive care units (ICU) at four medical institutions. PATIENTS: n = 3780 adults with ICU admission and diagnosis of COVID-19. INTERVENTIONS: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: (1) mortality; (2) discharge disposition; and (3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24 = greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). MEASUREMENTS AND MAIN RESULTS: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n = 1739) required mechanical ventilation. For 2191 patients who received rehabilitation, the dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2 = 0.68, p < 0.001) demonstrates mechanical ventilation (ß = - 0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p < 0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. CONCLUSIONS: Greater physical rehabilitation exposure early in the ICU is associated with better physical function at hospital discharge.

The Use of Telerehabilitation to Improve Movement-Related Outcomes and Quality of Life for Individuals With Parkinson Disease: Pilot Randomized Controlled Trial.

BACKGROUND: Individuals with Parkinson disease (PD) can improve their overall mobility and participation in daily activities as they engage in frequent exercise. Despite the need for individually tailored exercises, persons with PD often face barriers to accessing physical rehabilitation professionals who can provide them. Telerehabilitation (TR) may facilitate access to necessary and individually tailored rehabilitation for individuals with PD. OBJECTIVE: The purpose of this study was to assess the feasibility of TR for individuals with PD and explore clinical outcomes compared to in-person care. METHODS: This was a pilot randomized controlled trial conducted at 2 outpatient neurorehabilitation clinics with 3 study groups: clinic+TR, TR-only, and usual care (UC). TR was administered using a web-based application with a mobile app option. One-hour interventions were performed weekly for 4 weeks, in-person for the clinic+TR and UC groups and virtually for the TR-only group. Home exercises were provided on paper for the UC group and via the web-based platform for the clinic+TR and TR-only groups. Feasibility was assessed by recruitment and retention success and patient and therapist satisfaction, as rated in surveys. Clinical outcomes were explored using performance and patient-reported measures in between- and within-group analyses. RESULTS: Of 389 patients screened, 68 (17.5%) met eligibility criteria, and 20 (29.4% of those eligible) were enrolled (clinic+TR, n=6; TR-only, n=6; and UC, n=8). One patient (TR-only) was withdrawn due to a non-study-related injurious fall. Regardless of group allocation, both patients and therapists generally rated the mode of care delivery as "good" or "very good" across all constructs assessed, including overall satisfaction and safety. In the analysis of all groups, there were no differences in clinical outcomes at the discharge visit. Within-group differences (from baseline to discharge) were also generally not significant except in the UC group (faster 5-time sit-to-stand time and higher mini balance evaluation systems test balance score) and clinic+TR group (higher mini balance evaluation systems test balance score). CONCLUSIONS: High satisfaction amongst patients and clinicians regardless of group, combined with nonsignificant between-group differences in clinical outcomes, suggest that TR is feasible for individuals with PD in early-moderate stages. Future trials with a larger sample are necessary to test clinical effectiveness. As larger trials enroll patients with diverse characteristics (eg, in terms of age, disease progression, caregiver support, technology access and capacity, etc), they could begin to identify opportunities for matching patients to the optimal utilization of TR as part of the therapy episode. TRIAL REGISTRATION: ClinicalTrials.gov NCT06246747; https://clinicaltrials.gov/study/NCT06246747.

Inflammatory Cells in Control and Prolapsed Uterosacral Ligament Tissue.

Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted.

Use of the iPRISM webtool in a learning community to assess implementation context and fit of a novel clinical decision support tool for physical therapy triage in acute care hospitals.

BACKGROUND: The iPRISM webtool is an interactive tool designed to aid the process of applying the Practical, Robust Implementation and Sustainability Model (PRISM) for the assessment of and fit with context. A learning community (LC) is a multidisciplinary group of partners addressing a complex problem. Our LC coproduced the Physical TheraPy frEqueNcy Clinical decIsion support tooL (PT-PENCIL) to guide the use of physical therapist services in acute care hospitals. OBJECTIVE: To describe our LC's activities to co-produce the PT-PENCIL, use of the iPRISM webtool to assess its preimplementation context and fit, and develop a multicomponent implementation strategy for the PT-PENCIL. DESIGN: A descriptive research design. SETTING: Three tertiary care hospitals. PARTICIPANTS: Thirteen LC partners: six clinical physical therapists, three rehabilitation managers, three researchers, and a bioinformaticist. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Using the iPRISM webtool, expected fit of the PT-PENCIL was rated 1 (not aligned) to 6 (well aligned) for each PRISM domain and expected reach, effectiveness, adoption, implementation, and maintenance were rated 1 (not likely at all) to 6 (very likely). Discrete implementation strategies were identified from the Expert Recommendations for Implementing Change. RESULTS: The process spanned 18 meetings over 8 months. Ten LC partners completed the iPRISM webtool. PRISM domains with the lowest expected alignment were the "implementation and sustainability infrastructure" (mean = 4.7 out of 6; range = 3-6) and the "external environment" (mean = 4.9 of 6; range = 4-6). Adoption was the outcome with the lowest expected likelihood (mean = 4.5 out of 6; range = 1-6). Six discrete implementation strategies were identified and combined into a multicomponent strategy. CONCLUSIONS: Within a LC, we used existing implementation science resources to co-produce a novel clinical decision support tool for acute care physical therapists and develop a strategy for its implementation. Our methodology can be replicated for similar projects given the public availability of each resource used.

Early physical rehabilitation dosage in the IntensiveCare Unit predicts hospital outcomes after criticalCOVID-19.

Objective: to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions. Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19. Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2= 0.68, p <0.001) demonstrates mechanical ventilation (ß = -0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p <0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.

Medicare's Post-Acute Care Reimbursement Models as of 2023: Past, Present, and Future.

ABSTRACT: The Centers for Medicare & Medicaid Services is continually working to mitigate unnecessary expenditures, particularly in post-acute care (PAC). Medicare reimburses for orthopaedic surgeon services in varied models, including fee-for-service, bundled payments, and merit-based incentive payment systems. The goal of these models is to improve the quality of care, reduce health-care costs, and encourage providers to adopt innovative and efficient health-care practices.This article delves into the implications of each payment model for the field of orthopaedic surgery, highlighting their unique features, incentives, and potential impact in the PAC setting. By considering the historical, current, and future Medicare reimbursement models, we hope to provide an understanding of the optimal payment model based on the specific needs of patients and providers in the PAC setting.

Influence of sidewall retention and interference fit in total ankle replacement on implant-bone micromotion: A finite element study.

The success of uncemented total ankle replacement (TAR) is linked to initial stability because bony ingrowth depends upon limited early micromotion. Tibial implant design fixation features resist micromotion aided by bony sidewall retention and interference fit. Our goal was to investigate factors influencing implant-bone micromotion in TAR. Two TAR tibial components were virtually inserted into CT-derived computer models of two distal tibias from patients with end-stage ankle arthritis. Density-based inhomogeneous material assignment was used to model bone compaction during press-fit. Finite element analysis (FEA) was used to simulate three fixation cases: (1) no sidewalls + line-to-line fit, (2) sidewalls + line-to-line fit, and (3) sidewalls + 50, 100, or 200 µm interference fit. Kinetic profiles from the stance phase of gait were simulated and micromotions computed from FEA output. Without sidewalls or interference fit, micromotions were largest in early and late stance, with largest micromotions (averaging ~150-250 µm) observed near heel strike. Micromotions decreased 39%-62% when sidewalls were retained. When interference fit was also modeled, micromotions decreased another 37%-61% to ~10 µm. Micromotion differences between patients persisted with sidewall retention but largely disappeared with interference fit. This study presents new insights into the effects of TAR fixation features on implant-bone micromotion. Stability appeared to be influenced by surrounding bone quality, but this influence was greatly diminished when interference fit was introduced. More complete understanding of TAR implant features and performance is needed, but our results show the importance of bone quality and interference fit in the stability of uncemented TAR.

An atlas of gross and histologic lesions and immunohistochemical immunoreactivity during the temporal progression of aerosolized Lassa virus induced hemorrhagic fever in cynomolgus macaques.

Lassa virus (LASV) causes an acute multisystemic hemorrhagic fever in humans known as Lassa fever, which is endemic in several African countries. This manuscript focuses on the progression of disease in cynomolgus macaques challenged with aerosolized LASV and serially sampled for the development and progression of gross and histopathologic lesions. Gross lesions were first noted in tissues on day 6 and persisted throughout day 12. Viremia and histologic lesions were first noted on day 6 commencing with the pulmonary system and hemolymphatic system and progressing at later time points to include all systems. Immunoreactivity to LASV antigen was first observed in the lungs of one macaque on day 3 and appeared localized to macrophages with an increase at later time points to include immunoreactivity in all organ systems. Additionally, this manuscript will serve as a detailed atlas of histopathologic lesions and disease progression for comparison to other animal models of aerosolized Arenaviral disease.

A Single-shot ChAd3 Vaccine Provides Protection from Intramuscular and Aerosol Sudan Virus Exposure.

Infection with Sudan virus (SUDV) is characterized by an aggressive disease course with case fatality rates between 40-100% and no approved vaccines or therapeutics. SUDV causes sporadic outbreaks in sub-Saharan Africa, including a recent outbreak in Uganda which has resulted in over 100 confirmed cases in one month. Prior vaccine and therapeutic efforts have historically prioritized Ebola virus (EBOV), leading to a significant gap in available treatments. Two vaccines, Erbevo ® and Zabdeno ® /Mvabea ® , are licensed for use against EBOV but are ineffective against SUDV. Recombinant adenovirus vector vaccines have been shown to be safe and effective against filoviruses, but efficacy depends on having low seroprevalence to the vector in the target human population. For this reason, and because of an excellent safety and immunogenicity profile, ChAd3 was selected as a superior vaccine vector. Here, a ChAd3 vaccine expressing the SUDV glycoprotein (GP) was evaluated for immunogenicity and efficacy in nonhuman primates. We demonstrate that a single dose of ChAd3-SUDV confers acute and durable protection against lethal SUDV challenge with a strong correlation between the SUDV GP-specific antibody titers and survival outcome. Additionally, we show that a bivalent ChAd3 vaccine encoding the GP from both EBOV and SUDV protects against both parenteral and aerosol lethal SUDV challenge. Our data indicate that the ChAd3-SUDV vaccine is a suitable candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks. One Sentence Summary: A single-dose of ChAd3 vaccine protected macaques from lethal challenge with Sudan virus (SUDV) by parenteral and aerosol routes of exposure.

Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation.

BACKGROUND: Ovarian tissue cryopreservation has been proven to preserve fertility against gonadotoxic treatments. It has not been clear how this procedure would perform if planned for slowing ovarian aging. OBJECTIVE: This study aimed to determine the feasibility of cryopreserving ovarian tissue to extend reproductive life span and delay menopause by autotransplantation near menopause. STUDY DESIGN: Based on the existing biological data on follicle loss rates, a stochastic model of primordial follicle wastage was developed to determine the years of delay in menopause (denoted by D) by ovarian tissue cryopreservation and transplantation near menopause. Our model accounted for (1) age at ovarian tissue harvest (21-40 years), (2) the amount of ovarian cortex harvested, (3) transplantation of harvested tissues in single vs multiple procedures (fractionation), and (4) posttransplant follicle survival (40% [conservative] vs 80% [improved] vs 100% [ideal or hypothetical]). RESULTS: Our model predicted that, for most women aged <40 years, ovarian tissue cryopreservation and transplantation would result in a significant delay in menopause. The advantage is greater if the follicle loss after transplant can be minimized. As an example, the delay in menopause (D) for a woman with a median ovarian reserve who cryopreserves 25% of her ovarian cortex at the age of 25 years and for whom 40% of follicles survive after transplantation would be approximately 11.8 years, but this extends to 15.5 years if the survival is 80%. As another novel finding, spreading the same amount of tissue to repetitive transplants significantly extends the benefit. For example, for the same 25-year-old woman with a median ovarian reserve, 25% cortex removal, and 40% follicle survival, fractionating the transplants to 3 or 6 procedures would result in the corresponding delay in menopause (D) of 23 or 31 years. The same conditions (3 or 6 procedures) would delay menopause as much as 47 years if posttransplant follicle survival is improved to 80% with modern approaches. An interactive Web tool was created to test all variables and the feasibility of ovarian tissue freezing and transplantation to delay ovarian aging (here). CONCLUSION: Our model predicts that with harvesting at earlier adult ages and better transplant techniques, a significant menopause postponement and, potentially, fertile life span extension can be achieved by ovarian tissue cryopreservation and transplantation in healthy women.

High Risk of Readmission After THA Regardless of Functional Status in Patients Discharged to Skilled Nursing Facility.

BACKGROUND: The postoperative period and subsequent discharge planning are critical in our continued efforts to decrease the risk of complications after THA. Patients discharged to skilled nursing facilities (SNFs) have consistently exhibited higher readmission rates compared with those discharged to home healthcare. This elevated risk has been attributed to several factors but whether readmission is associated with patient functional status is not known. QUESTIONS/PURPOSES: After controlling for relevant confounding variables (functional status, age, gender, caregiver support available at home, diagnosis [osteoarthritis (OA) versus non-OA], Charlson comorbidity index [CCI], the Area Deprivation Index [ADI], and insurance), are the odds of 30- and 90-day hospital readmission greater among patients initially discharged to SNFs than among those treated with home healthcare after THA? METHODS: This was a retrospective, comparative study of patients undergoing THA at any of 11 hospitals in a single, large, academic healthcare system between 2017 and 2022 who were discharged to an SNF or home healthcare. During this period, 13,262 patients were included. Patients discharged to SNFs were older (73 ± 11 years versus 65 ± 11 years; p < 0.001), less independent at hospital discharge (6-click score: 16 ± 3.2 versus 22 ± 2.3; p < 0.001), more were women (71% [1279 of 1796] versus 56% [6447 of 11,466]; p < 0.001), insured by Medicare (83% [1497 of 1796] versus 52% [5974 of 11,466]; p < 0.001), living in areas with greater deprivation (30% [533 of 1796] versus 19% [2229 of 11,466]; p < 0.001), and had less assistance available from at-home caregivers (29% [527 of 1796] versus 57% [6484 of 11,466]; p < 0.001). The primary outcomes assessed in this study were 30- and 90-day hospital readmissions. Although the system automatically flags readmissions occurring within 90 days at the various facilities in the overall healthcare system, readmissions occurring outside the system would not be captured. Therefore, we were not able to account for potential differential rates of readmission to external healthcare systems between the groups. However, given the large size and broad geographic coverage of the healthcare system analyzed, we expect the readmissions data captured to be representative of the study population. The focus on a single healthcare system also ensures consistency in readmission identification and reporting across subjects. We evaluated the association between discharge disposition (home healthcare versus SNF) and readmission. Covariates evaluated included age, gender, primary payer, primary diagnosis, CCI, ADI, the availability of at-home caregivers for the patient, and the Activity Measure for Post-Acute Care (AM-PAC) 6-clicks basic mobility score in the hospital. The adjusted relative risk (ARR) of readmission within 30 and 90 days of discharge to SNF (versus home healthcare) was estimated using modified Poisson regression models. RESULTS: After adjusting for the 6-clicks mobility score, age, gender, ADI, OA versus non-OA, living environment, CCI, and insurance, patients discharged to an SNF were more likely to be readmitted within 30 and 90 days compared with home healthcare after THA (ARR 1.46 [95% CI 1.01 to 2.13]; p= 0.046 and ARR 1.57 [95% CI 1.23 to 2.01]; p < 0.001, respectively). CONCLUSION: Patients discharged to SNFs after THA had a slightly higher likelihood of hospital readmission within 30 and 90 days compared with those discharged with home healthcare. This difference persisted even after adjusting for relevant factors like functional status, home support, and social determinants of health. These results indicate that for suitable patients, direct home discharge may be a safer and more cost-effective option than SNFs. Clinicians should carefully consider these risks and benefits when making postoperative discharge plans. Policymakers could consider incentives and reforms to improve care transitions and coordination across settings. Further research using robust methods is needed to clarify the reasons for higher SNF readmission rates. Detailed analysis of patient complexity, care processes, and causes of readmission in SNFs versus home health could identify areas for quality improvement. Prospective cohorts or randomized trials would allow stronger conclusions about cause-and-effect. Importantly, no patients should be unfairly "cherry-picked" or "lemon-dropped" based only on readmission risk scores. With proper support and care coordination, even complex patients can have good outcomes. The goal should be providing excellent rehabilitation for all, while continuously improving quality, safety, and value across settings. LEVEL OF EVIDENCE: Level III, therapeutic study.