Immunometabolic regulation of germinal centers and its implications for aging.

Aging, metabolism, and immunity have long been considered distinct domains. Aging is primarily associated with the gradual decline of physiological functions, metabolism regulates energy production and maintains cellular processes, and the immune system manages innate and adaptive responses against pathogens and vaccines. However, recent studies have revealed that these three systems are intricately interconnected, collectively influencing an individual's response to stress and disease. This review explores the interplay between immunometabolism, T follicular helper cells, B cells, and aging, focusing on how these interactions impact immune function in the elderly.

In Vivo Deformation of the Human Basilar Artery.

An estimated 6.8 million people in the United States have an unruptured intracranial aneurysms, with approximately 30,000 people suffering from intracranial aneurysms rupture each year. Despite the development of population-based scores to evaluate the risk of rupture, retrospective analyses have suggested the limited usage of these scores in guiding clinical decision-making. With recent advancements in imaging technologies, artery wall motion has emerged as a promising biomarker for the general study of neurovascular mechanics and in assessing the risk of intracranial aneurysms. However, measuring arterial wall deformations in vivo itself poses several challenges, including how to image local wall motion and deriving the anisotropic wall strains over the cardiac cycle. To overcome these difficulties, we first developed a novel in vivo MRI-based imaging method to acquire cardiac gated images of the human basilar artery (BA) over the cardiac cycle. Next, complete BA endoluminal surfaces from each frame were segmented, producing high-resolution point clouds of the endoluminal surfaces. From these point clouds we developed a novel B-spline-based surface representation, then exploited the local support nature of B-splines to determine the local endoluminal surface strains. Results indicated distinct regional and temporal variations in BA wall deformation, highlighting the heterogeneous nature BA function. These included large circumferential strains (up to ∼ 20 % ), and small longitudinal strains, which were often contractile and out of phase with the circumferential strains patterns. Of particular interest was the temporal phase lag in the maximum circumferential perimeter length, which indicated that the BA deforms asynchronously over the cardiac cycle. In summary, the proposed method enabled local deformation analysis, allowing for the successful reproduction of local features of the BA, such as regional principal stretches, areal changes, and pulsatile motion. Integrating the proposed method into existing population-based scores has the potential to improve our understanding of mechanical properties of human BA and enhance clinical decision-making.

A retrospective analysis of 513 patients undergoing pedicle subtraction osteotomy for adult spinal deformity by a single surgical team: are elderly patients at an elevated risk for complications?

OBJECTIVE: This study aimed to assess whether elderly patients (aged ≥ 70 years) face an elevated risk of complications following pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD) compared with younger patients (< 70 years) and to evaluate if clinical and radiological outcomes differ between these age groups. METHODS: A retrospective analysis of 513 patients undergoing PSO for ASD by a single surgical team between January 2006 and January 2023 was conducted. Patients were categorized by age (≥ 70 years and < 70 years). Data on clinical, demographic, comorbidity, and radiographic details were collected and compared between the groups. For health-related quality of life assessment, the authors recorded the Oswestry Disability Index (ODI), numeric rating scale (NRS), and Scoliosis Research Society-22 revised (SRS-22r) scores preoperatively and at 6 weeks and 1 year postoperatively. Perioperative complications included major (neurological deficit, death, acute myocardial infarction, stroke), minor (ileus, arrhythmia, delirium), and intraoperative (durotomy, vascular injury). RESULTS: Of 513 patients, 412 were included in the study. Clinical outcomes, as measured by NRS, ODI, and SRS-22r scores, were comparable between groups, with both groups showing significant improvements postoperatively. Radiographic outcomes also showed significant and comparable improvements in sagittal balance and spinopelvic harmony in both groups. Deformity corrections were also well maintained at 1 year postoperatively. The elderly group (mean age 75.48 years) had a higher rate of perioperative complications (44.64%) than the younger group (mean age 59.60 years; 30.33%) (p = 0.0030), primarily minor complications such as delirium and arrhythmia (16.07% vs 8.61%, p = 0.0279). There was no significant difference between groups regarding the major complication rate (elderly group: 20.83% vs younger group: 14.34%, p = 0.1087), intraoperative complication rate (2.98% vs 3.69%, p = 0.6949), short-term complication rate (10.12% vs 8.20%, p = 0.5024), mechanical complication rate (30.95% vs 32.79%, p = 0.6949), and reoperation rate due to mechanical complications (38.46% vs 43.75% p = 0.5470). CONCLUSIONS: Elderly patients undergoing PSO for ASD experience a higher rate of minor complications but can achieve clinical and radiological outcomes that are comparable to those of younger patients. The authors found no significant increase in major, intraoperative, short-term, or mechanical complication rates and their subsequent reoperation rates among the elderly. These findings underscore the effectiveness of PSO in improving the quality of life for patients with ASD across age groups, emphasizing the critical role of personalized perioperative management in enhancing outcomes and minimizing risks for all patients.

Assessing the Predictive Validity of Early Post-injury CAPS-5 for Later Posttraumatic Stress Disorder Diagnosis.

Abstract.Objective: The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a widely recognized tool with exceptional reliability and validity in evaluating and diagnosing PTSD. This study aimed to determine the predictive values of CAPS-5 assessed early postinjury for subsequent development of PTSD during a 2-year follow-up period.Methods: Patients with moderate to severe physical injuries were recruited from a trauma center at a university hospital in South Korea between June 2015 and January 2021. At baseline, 1,142 patients underwent evaluations using CAPS-5 for the diagnosis of acute stress disorder (ASD) along with total scores. They were followed up for PTSD using the CAPS-5 evaluations at 3, 6, 12, and 24 months post-baseline. Area under receiver operating curve (AUROC) analyses were conducted to identify predictive values of the CAPS-5 for later PTSD development.Results: CAPS-5 diagnosis of ASD at baseline displayed fair to failed performance (AUROCs: 0.555-0.722) for predicting follow-up PTSD. However, CAPS-5 scores of ≥15 exhibited good to fair predictive accuracy (AUROCs: 0.767-0.854) for later PTSD development. Notably, for patients with intentional injuries or a history of previous trauma, a higher CAPS-5 score of ≥16 showed improved predictive accuracy.Conclusion: A CAPS-5 score of ≥15 would be an effective and practical cutoff for early prediction of PTSD following physical injuries. In cases of intentional injuries or a documented trauma history, a cutoff of ≥16 may offer enhanced predictive precision. Future research in diverse settings and populations is needed to confirm the generalizability of our findings.

Interaction Effect of Childhood Abuse History and Suicidality on 12-Month Antidepressant Response in Patients With Depressive Disorder.

OBJECTIVE: We aimed to identify the individual and interactive effects of childhood abuse and suicidal ideation on antidepressant treatment response in 12 months. METHODS: In this prospective research, 1,262 depressive patients were asked about their childhood abuse history, suicidal ideation, and other clinical characteristics and socio-demographic features at baseline, and 1,015 of them were followed during 1 year of stepwise pharmacotherapy. The individual and interactive relationships of the childhood abuse history and suicidal ideation on 12-month antidepressant non-remission were explored by logistic regression with relevant covariates. RESULTS: Having a childhood abuse history and higher suicidal ideation significantly predicted a non-remission state in 12 months respectively. The interaction term of childhood abuse and suicidal ideation was also significantly related to a non-remission state at 12 months. To be specific, in the low suicidal ideation group, depressive patients with a childhood abuse history were more likely to be in a non-remission state after 12 months of medication. In the high suicidal ideation group, however, childhood abuse history was not significantly associated with the non-remission state at 12 months. CONCLUSION: The childhood abuse history and the level of suicidal ideation are informative factors predicting the long-term results of antidepressant treatment, especially when they are combined. Clinicians may consider antidepressants with a higher affinity for patients with childhood abuse history even if they don't have suicidal ideation. The cognitive intervention for suicidal ideation might be helpful in addition to pharmacological treatment.

Serum cortisol and neuroticism for post-traumatic stress disorder over 2 years in patients with physical injuries.

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

Harmonic errors of a 9.4 T all-REBCO NMR magnet affected by screening current and geometric inconsistency of coated conductors.

REBa 2 Cu 3 O 7 - x (REBCO, RE = rare earth)-coated conductor is a competitive option in terms of current-carrying capacity and high-stress durability in developing high-field magnets for nuclear magnetic resonance (NMR) research. Meanwhile, a technical challenge in utilizing a stand-alone REBCO NMR magnet is an unexpected difference in the field uniformity between the designed and measured values after being constructed and charged, i.e., harmonic errors. Bortot et al., and Li et al., reported analytic evidence of the related issue. However, sufficient research has not yet been conducted, so evidence should be supplemented further. Here we report harmonic errors due to screening current and inconsistent conductor thickness, confirmed by a 400 MHz 1H NMR magnet development project. The magnet was first charged up to its operating current, and then multiple overcharge-discharge cycles were applied, which was an empirically optimized operation protocol. A field mapping device obtained magnetic fields at designated locations in the room-temperature bore. The result showed over 100 ppm field uniformity difference between designed and measured values. A simulation model was developed considering screening current and inconsistent conductor thickness for reproducing the field distribution. Comparison of voltages and fields between simulation and measurement validated the model. Further analysis of the overcharge-discharge effect on harmonic errors demonstrated that even and odd-order harmonics are mainly attributed to screening current and geometric inconsistency while confirming the limitation of the screening current mitigation effect. Hence, we concluded that the desirable requirement of the sub-ppm level field uniformity generation might be barely possible with the current REBCO NMR magnet design approach.

Modeling the mechanosensitive collective migration of cells on the surface and the interior of morphing soft tissues.

Cellular contractility, migration, and extracellular matrix (ECM) mechanics are critical for a wide range of biological processes including embryonic development, wound healing, tissue morphogenesis, and regeneration. Even though the distinct response of cells near the tissue periphery has been previously observed in cell-laden microtissues, including faster kinetics and more prominent cell-ECM interactions, there are currently no models that can fully combine coupled surface and bulk mechanics and kinetics to recapitulate the morphogenic response of these constructs. Mailand et al. (Biophys J 117(5):975-986, 2019) had shown the importance of active elastocapillarity in cell-laden microtissues, but modeling the distinct mechanosensitive migration of cells on the periphery and the interior of highly deforming tissues has not been possible thus far, especially in the presence of active elastocapillary effects. This paper presents a framework for understanding the interplay between cellular contractility, migration, and ECM mechanics in dynamically morphing soft tissues accounting for distinct cellular responses in the bulk and the surface of tissues. The major novelty of this approach is that it enables modeling the distinct migratory and contractile response of cells residing on the tissue surface and the bulk, where concurrently the morphing soft tissues undergo large deformations driven by cell contractility. Additionally, the simulation results capture the changes in shape and cell concentration for wounded and intact microtissues, enabling the interpretation of experimental data. The numerical procedure that accounts for mechanosensitive stress generation, large deformations, diffusive migration in the bulk and a distinct mechanism for diffusive migration on deforming surfaces is inspired from recent work on bulk and surface poroelasticity of hydrogels involving elastocapillary effects, but in this work, a two-field weak form is proposed and is able to alleviate numerical instabilities that were observed in the original method that utilized a three-field mixed finite element formulation.