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Varicella zoster virus (VZV) is a highly contagious human herpes virus responsible for causing chickenpox (varicella) and shingles (herpes zoster). Despite the approval of a highly effective vaccine, Shingrix®, the global incidence of herpes zoster is increasing and the economic burden to the health care system and society are substantial due to significant loss of productivity and health complications, particularly among elderly and immunocompromised individuals. This is primarily because access to the vaccines remains mostly limited to countries within developed economies, such as USA and Canada. Therefore, similarly effective vaccines against VZV that are more accessible to the rest-of-the-world are necessary. In this study, we aimed to evaluate immunogenicity and memory response induced by three mRNA-LNP-based vaccine candidates targeting VZV's surface glycoprotein E (gE). C57BL/6 mice were immunized with each candidate vaccine, and humoral and cellular immune responses were assessed. Our results demonstrate that the mRNA-LNP-based vaccine candidates elicited robust and durable humoral responses specific to the gE antigen. Notably, mice vaccinated with the mRNA-LNP vaccines exhibited significantly higher antigen-specific T-cell cytokine production compared to the group receiving Shingrix®, the current standard of care vaccine. Additionally, mRNA-LNP vaccines induced long-lasting memory response, as evidenced by detection of persistent gE-specific Long-Lived Plasma Cells (LLPCs) and memory T cells four months after final immunization. These findings underscore the potential of our mRNA-LNP-based vaccine candidates in generating potent immune responses against VZV, offering promising prospects for their clinical development as an effective prophylactic vaccine against herpes zoster. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematode (GIN) parasite infections can be detrimental to not only cattle health and immunity, but also result in economic loss and poor performance. Cattle grazing in the southeast are challenged even further by the favorable environmental conditions for parasite development, especially those animals who have yet to develop an immunity to combat parasitism. To diminish potential economic and performance-based losses, many beef producers treat animals for GIN parasites with anthelmintics on a regular basis without proper diagnosis. Anthelmintic resistance(AR) develops when deworming products are overused and misused. To minimize the development of AR, selective deworming and sustainable management practices should be implemented. However, the severity of parasite burden over the production cycle needs to be better understood in beef cattle herds before recommendations can be made. Thus, the objective was to investigate the rates of GIN parasite infections through fecal egg counts (FEC) and the impact on body weight (BW) and body condition score (BCS). Angus-based cattle (6 mo-13 yr, n = 1,154) on a were utilized from five different research and educational herds across North Carolina. Cattle were categorized based on their age at the start of the project as either calves (n = 446), yearling heifers (n = 205), 2 year old (n = 260), 3-5 year old (n = 501), or 6+ year old (n = 206). Starting in September, FEC, BW, and BCS were collected and analyzed every 90 d at critical production timepoints (calving, breeding, weaning, and 90d post-weaning) to monitor the severity of GIN parasite challenge. Cattle on study were not treated with anthelmintics regardless of parasite load, with the exception of calves at four of the locations at the time of weaning. All data were analyzed using Proc MIXED in SAS with repeated measures. Statistical significance was declared at P ≤ 0.05 and a trend at 0.10 > P > 0.05. Age of cattle had an impact on FEC overall (P < 0.05), however, there was no difference between FEC of mature cattle over 3 yr (4.29 ± 4.9 eggs/gm). Calves had the greatest FEC (120.59 ± 4.2 eggs/gm) while cattle 6+ yr had the least (3.68 ± 4.5 eggs/gm). Cattle age at each location affected BCS and BW (P < 0.05). Between age groups across locations, time had an impact on FEC, BW, and BCS (P < 0.05). There was also a tendency (P = 0.6) for location to impact FEC. Calf sex did not affect (P > 0.05) FEC. Further FEC analysis of cattle under 2 yrof age is required to better understand when a natural immune response to GIN parasite infections develops. [ABSTRACT FROM AUTHOR]

Background: Remote patient monitoring (RPM) is an emerging focus in health care, and specialized programs may reduce medical costs, supplement in-office visits, and improve patient satisfaction. In this study, we describe the development, feasibility, and early outcomes of an RPM program for patients with decompensated cirrhosis., Methods: Forty-six patients were offered enrollment at the time of hospital discharge in the cirrhosis RPM program (CiRPM), of which 41 completed at least 30 days of monitoring. Participants were mailed remote monitoring equipment and a tablet to be used for patient-reported outcomes. Alerts were continuously monitored by virtual nursing staff who could perform targeted interventions. A cohort of historical controls (n = 74) was created for comparison using inverse probability of treatment weighting., Results: Patients were enrolled in the program for a mean of 83.9 days, with 28 (68%) completing the full 90-day program. Participants uploaded vital signs and responded to symptom-based questionnaires on 93% of the monitored days. On end-of-program surveys, over 75% of patients expressed satisfaction with the program. Gender, age, and MELD-Na were similar between CiRPM and weighted control groups. The 90-day readmission rate was 34% in CiRPM and 47% in weighted controls. In the CiRPM group, 12% of subjects had 2 or more admissions, compared to 37% in the weighted control group., Conclusion: This study demonstrates the feasibility of a cirrhosis-specific RPM program. Overall, patient satisfaction and utilization of the CiRPM was high. Future studies are needed to confirm the impact of RPM on the reduction of hospital readmissions in decompensated cirrhosis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing. In this study, we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway, a molecular driver of endochondral ossification. We hypothesize that using an mRNA-based therapeutic encoding β-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes. To optimize a delivery platform built on recent advancements in liposomal technologies, two FDA-approved ionizable phospholipids, DLin-MC3-DMA (MC3) and SM-102, were used to fabricate unique ionizable lipid nanoparticle (LNP) formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model. Using firefly luciferase mRNA as a reporter gene to track and quantify transfection, SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection, minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs. The generated β-catenin GOF mRNA encapsulated in SM-102 LNPs (SM-102-β-catenin GOF mRNA) showed bioactivity in vitro through upregulation of downstream canonical Wnt genes, axin2 and runx2 . When testing SM-102-β-catenin GOF mRNA therapeutic in a murine tibia fracture model, histomorphometric analysis showed increased bone and decreased cartilage composition with the 45 μg concentration at 2 weeks post-fracture. μCT testing confirmed that SM-102-β-catenin GOF mRNA promoted bone formation in vivo , revealing significantly more bone volume over total volume in the 45 μg group. Thus, we generated a novel mRNA-based therapeutic encoding a β-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery., Competing Interests: Anna Laura Nelson, Chiara Mancino, Xueqin Gao, Josh Choe, Laura Chubb, Katherine Williams, Molly Czachor, Ralph Marcucio and Francesca Taraballi have nothing to disclose. Dr. Johnny Huard discloses an unpaid position on the leadership for Orthopaedic Research Society (ORS). JH discloses royalties from Cook Myosite, Inc. Dr. Cooke is on the Scientific Advisory Board of Humann Inc, which makes products related to nitric oxide and cardiovascular health; is an inventor on multiple patents assigned to Stanford University or Houston Methodist Hospital related to endothelial function and regeneration; and has been a collaborator and co-author with Dr. Zhen Chen. Dr. Chelsea Bahney discloses an unpaid position on the leadership for Orthopaedic Research Society (ORS), Tissue Engineering and Regenerative Medicine International Society (TERMIS), and the Orthopaedic Trauma Association (OTA). CB also discloses IP royalties from Iota Biosciences, Inc. for US Patent 041263 and a Review Editor role for Frontiers in Skeletal Physiology. Dr. Nicole Ehrhart discloses paid consultant positions for Onkos Surgical Inc. and Ripple Neuromed Inc. ALN, CM, JH, RM, JCooke, FT, CB, NE also disclose inventorship on PCT/US2022 Application No. 63/155,263, entitled MCM For Gene Therapy to Activate Wnt Pathway. These entities provided no funding for this research and there are no conflicts of interest with the work presented in this manuscript. Anna Laura Nelson, Dr. Johnny Huard, Dr. Xueqin Gao, Molly Czachor and Dr. Chelsea Bahney are all paid employees of the non-profit Steadman Philippon Research Institute (SPRI). SPRI exercises special care to identify any financial interests or relationships related to research conducted here. During the past calendar year, SPRI has received grant funding or in-kind donations from Arthrex, DJO, MLB, Ossur, Siemens, Smith & Nephew, XTRE, and philanthropy. These funding sources provided no support for the work presented in this manuscript unless otherwise noted., (© 2024 The Authors.)

Following immunization, lymph nodes dynamically expand and contract. The mechanical and cellular changes enabling the early-stage expansion of lymph nodes have been characterized, yet the durability of such responses and their implications for adaptive immunity and vaccine efficacy are unknown. Here, by leveraging high-frequency ultrasound imaging of the lymph nodes of mice, we report more potent and persistent lymph-node expansion for animals immunized with a mesoporous silica vaccine incorporating a model antigen than for animals given bolus immunization or standard vaccine formulations such as alum, and that durable and robust lymph-node expansion was associated with vaccine efficacy and adaptive immunity for 100 days post-vaccination in a mouse model of melanoma. Immunization altered the mechanical and extracellular-matrix properties of the lymph nodes, drove antigen-dependent proliferation of immune and stromal cells, and altered the transcriptional features of dendritic cells and inflammatory monocytes. Strategies that robustly maintain lymph-node expansion may result in enhanced vaccination outcomes., (© 2024. The Author(s).)

Background and Aim: Recent studies have shown that up to 53% of patients with inflammatory bowel disease (IBD) screen positive for avoidant/restrictive food intake disorder (ARFID). There is however concern that ARFID screening rates are over-inflated in patients with active disease. We aimed to evaluate the frequency and characteristics of ARFID symptoms using the Nine Item ARFID Screen (NIAS), and to use another eating disorder measure, the Eating Disorder Examination-Questionnaire 8 (EDE-Q8), to rule-out/characterize other eating disorder cognitive and behavioral symptoms., Methods: Participants included adults with UC who are enrolled in an in an ongoing cohort study with quiescent UC (SCCAI ≤2 or fecal calprotectin <150 µg/g with corticosteroid-free clinical remission for ≥ 3 months) at baseline. We used self-reported data on demographics, gastrointestinal medications, medical comorbidities, NIAS scores, and other eating disorder symptom scores (8-item Eating Disorder Examination-Questionnaire; EDE-Q-8)., Results: We included 101 participants who completed the NIAS at their baseline cohort assessment (age 49.9±16.5 years; 55% female). Eleven participants (11%) screened positively for ARFID on at least one NIAS subscale (n=8 male). Up to thirty participants (30%) screened positive for other eating disorder symptoms (EDE-Q-8 Global ≥2.3). Overall score distributions on the EDE-Q-8 showed that participants scored highest on the Weight Concern and Shape Concern subscales., Conclusions: Among adults with UC in remission, we found a low rate of ARFID symptoms by the NIAS but a high rate of positive screens for other eating disorder symptoms., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)