Rupture of abdominal aortic aneurysms (AAAs) alone is the thirteenth leading cause of death in the United States. Thus, reliable AAA-rupture risk prediction is an important advancement. If repair ...becomes necessary, the minimally invasive technique of inserting a stent-graft (SG), commonly referred to as endovascular aneurysm repair (EVAR), is a viable option in many cases. However, postoperative complications, such as endoleaks and/or SG migration, may occur. Computational fluid-structure interaction simulations provide physical insight into the hemodynamics coupled with multi-wall mechanics' function as an assessment tool for optimal SG placement and improved device design.
Direct measurements revealed low oxygen tensions (0.5-4.5% oxygen) in murine lymphoid organs in vivo. To test whether adaptation to changes in oxygen tension may have an effect on lymphocyte ...functions, T cell differentiation and functions at varying oxygen tensions were studied. These studies show: 1) differentiated CTL deliver Fas ligand- and perforin-dependent lethal hit equally well at all redox conditions; 2) CTL development is delayed at 2.5% oxygen as compared with 20% oxygen. Remarkably, development of CTL at 2.5% oxygen is more sustained and the CTL much more lytic; and 3) hypoxic exposure and TCR-mediated activation are additive in enhancing levels of hypoxia response element-containing gene products in lymphocyte supernatants. In contrast, hypoxia inhibited the accumulation of nonhypoxia response element-containing gene products (e.g., IL-2 and IFN-gamma) in the same cultures. This suggests that T cell activation in hypoxic conditions in vivo may lead to different patterns of lymphokine secretion and accumulation of cytokines (e.g., vascular endothelial growth factor) affecting endothelial cells and vascular permeabilization. Thus, although higher numbers of cells survive and are activated during 20% oxygen incubation in vitro, the CTL which develop at 2.5% oxygen are more lytic with higher levels of activation markers. It is concluded that the ambient 20% oxygen tension (plus 2-ME) is remarkably well suited for immunologic specificity and cytotoxicity studies, but oxygen dependence should be taken into account during the design and interpretation of results of in vitro T cell development assays and gene expression studies in vivo.
This paper presents a fully automated method for segmenting articular knee cartilage and bone from in vivo 3-D dual echo steady state images. The magnetic resonance imaging (MRI) datasets were ...obtained from the Osteoarthritis Initiative (OAI) pilot study and include longitudinal images from controls and subjects with knee osteoarthritis (OA) scanned twice at each visit (baseline, 24 month). Initially, human experts segmented six MRI series. Five of the six resultant sets served as reference atlases for a multiatlas segmentation algorithm. The methodology created precise knee segmentations that were used to extract articular cartilage volume, surface area, and thickness as well as subchondral bone plate curvature. Comparison to manual segmentation showed Dice similarity coefficient (DSC) of 0.88 and 0.84 for the femoral and tibial cartilage. In OA subjects, thickness measurements showed test-retest precision ranging from 0.014 mm (0.6%) at the femur to 0.038 mm (1.6%) at the femoral trochlea. In the same population, the curvature test-retest precision ranged from 0.0005 mm -1 (3.6%) at the femur to 0.0026 mm -1 (11.7%) at the medial tibia. Thickness longitudinal changes showed OA Pearson correlation coefficient of 0.94 for the femur. In conclusion, the fully automated segmentation methodology produces reproducible cartilage volume, thickness, and shape measurements valuable for the study of OA progression.
The purpose of this study was to evaluate the effect of directional branches (DBs) bridging stent choice on target artery (TA) outcomes during fenestrated-branched endovascular repair of complex ...abdominal and thoracoabdominal aortic aneurysms.
Patients enrolled in nine prospective physician-sponsored investigational device exemption studies in the United States between 2005 and 2020 were analyzed. All patients who had at least one TA incorporated by DB using either self-expandable (SESGs), balloon-expandable (BESGs), or hybrid stent graft combinations (HSGs). Endpoints were TA patency and freedom from TA endoleak, instability, and reintervention.
There were 800 patients with 2426 renal-mesenteric arteries incorporated by DBs. DB stent selection was SESGs in 1205 TAs (50%), BESGs in 1095 TAs (45%), and HSGs in 126 TAs (5%). SESGs were predominantly used in the first three quartiles of the study period, whereas BESGs comprised 75% of all stents between 2017 and 2020. The median follow-up was 15 months (interquartile range, 6-35 months). At 5 years, BESGs had significantly lower freedom from TA instability (78% ± 4% vs 88% ± 1% vs 96% ± 2%; log-rank P =.010), freedom from TA endoleaks (87% ± 3% vs 97% ± 1% vs 99% ± 1%; log-rank P < .001), and freedom from TA reintervention (83% ± 4% vs 95% ± 1% vs 99% ± 2%; log-rank P <.001) compared with SESGs or HSGs, respectively. For renal arteries, there was no difference in freedom from TA instability for BESGs, SESGs, or HSGs. However, freedom from TA endoleaks and reintervention were lower for renal arteries targeted by BESGs compared with DBs targeted by SESGs and HSGs (83% ± 6% vs 98% ± 1% vs 100%; log-rank P < .001; and 70% ± 10% vs 92% ± 1% vs 96% ± 4%; log-rank P = .022). For mesenteric arteries, DBs targeted by BESGs had lower freedom from TA instability, endoleak, and reintervention than SESGs or HSGs. In stent-specific analysis, iCAST BESGs had the lowest freedom from TA instability either for renal or mesenteric arteries, primarily due to higher rates of TA endoleaks. There was no difference in patency in any scenario. Independent predictors of TA instability were age (+1-year: hazard ratio HR, 0.97; 95% confidence interval CI, 0.94-0.99), stent diameter (+1 mm: HR, 0.67; 95% CI, 0.57-0.80), and BESG (HR, 1.8; 95% CI, 1.1-2.9).
DBs incorporated using BESGs had lower freedom from TA instability, TA endoleak, and TA reintervention compared with SESGs and HSGs. The patency of DBs was not affected by the type of stent construction. The observed performance disadvantage associated with BESGs appears to have largely been driven by iCAST usage.
The nanostructure of the wood cell wall and, in particular the tilt angle of the cellulose fibrils versus the longitudinal cell axis (microfibril angle, MFA), are known to play a key role in ...determining the mechanical properties of wood. A variation of microfibril angles during growth may therefore be regarded as a means to adapt to different loading situations. In the present study, a branch of Norway spruce (Picea abies) was used as a model system. The change of microfibril angles with increasing age and size of the branch and therefore increasing gravitational load was systematically investigated. Small angle X-ray scattering (SAXS) was applied to obtain a map of MFA all over the branch as a function of the distance from the trunk within each annual ring. It was found that in compression wood the MFA decreased continuously from the trunk towards the tip in all annual rings. In opposite wood, however, the course of microfibril angles was found to change considerably with the age of the branch: in the outer annual rings, very small microfibril angles occurred in the middle part of the branch. The results are discussed in view of the mechanical implications of different microfibril angles.
Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized ...prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System PROMIS) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models.
In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery.
A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain.
The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.
Depression is a common illness in people with HIV (PWH) and is associated with substantial morbidity and mortality. The mechanisms that underpin depression in PWH remain incompletely elucidated, and ...more research is therefore needed to develop effective treatments. One hypothesis is that neurotransmitter levels may be altered. These levels could be influenced by the chronic inflammation and viral persistence that occurs in PWH. We examined a panel of cerebrospinal fluid (CSF) neurotransmitters in PWH on suppressive antiretroviral therapy (ART), many of whom had a current depression diagnosis. CSF monoamine neurotransmitters and their metabolites were measured from participants in studies at the Emory Center for AIDS Research (CFAR). Only participants on stable ART with suppressed HIV RNA from both plasma and CSF were analyzed. Neurotransmitter levels were measured with high-performance liquid chromatography (HPLC). Neurotransmitters and their metabolites included dopamine (DA), homovanillic acid (HVA, a major metabolite of dopamine), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA, a major metabolite of serotonin), and 4-hydroxy-3-methoxyphenylglycol (MHPG, a major metabolite of norepinephrine). Multivariable logistic regression was used to evaluate factors associated with depression. There were 79 PWH with plasma and CSF HIV RNA levels < 200 copies/mL at the time of the visit, and 25 (31.6%) carried a current diagnosis of depression. Participants with depression were significantly older (median age 53 years versus 47 years,
P
= 0.014) and were significantly less likely to be African American (48.0% versus 77.8%,
P
= 0.008). Participants with depression had significantly lower dopamine levels (median 0.49 ng/mL versus 0.62 ng/mL,
P
= 0.03) and significantly lower 5-HIAA levels (median 12.57 ng/mL versus 15.41 ng/mL,
P
= 0.015). Dopamine and 5-HIAA were highly correlated. In the multivariable logistic regression models, lower 5-HIAA was significantly associated with the depression diagnosis when accounting for other significant demographic factors. The associations between lower 5-HIAA, lower dopamine, and depression in PWH suggest that altered neurotransmission may contribute to these comorbid conditions. However, the effects of antidepressants on neurotransmitters cannot be ruled out as a factor in the 5-HIAA results.
Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The ...mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0-13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4
T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and immunoglobulin class switching and exhibit a more activated profile than lymph node B cells. Moreover, B cells in the lung and lung-associated lymph nodes generate biased antibody responses to multiple respiratory pathogens compared to circulating antibodies, which are mostly specific for vaccine antigens in the early years of life. Together, our findings provide evidence for BALT as an early life adaptation for mobilizing localized immune protection to the diverse respiratory challenges during this formative life stage.
Epidemics caused by long-distance dispersed pathogens result in some of the most explosive and difficult to control diseases of both plants and animals (including humans). Yet the factors influencing ...disease spread, especially in the early stages of the outbreak, are not well-understood. We present scaling relationships, of potentially widespread relevance, that were developed from more than 15 years of field and in silico single focus studies of wheat stripe rust spread. These relationships emerged as a consequence of accounting for a greater proportion of the fat-tailed disease gradient that may be frequently underestimated in disease spread studies. Leptokurtic dispersal gradients (highly peaked and fat-tailed) are relatively common in nature and they can be represented by power law functions. Power law scale invariance properties generate patterns that repeat over multiple spatial scales, suggesting important and predictable scaling relationships between disease levels during the first generation of disease outbreaks and subsequent epidemic spread. Experimental wheat stripe rust outbreaks and disease spread simulations support theoretical scaling relationships from power law properties and suggest that relatively straightforward scaling approximations may be useful for projecting the spread of disease caused by long-distance dispersed pathogens. Our results suggest that, when actual dispersal/disease data are lacking, an inverse power law with exponent = 2 may provide a reasonable approximation for modeling disease spread. Furthermore, our experiments and simulations strongly suggest that early control treatments with small spatial extent are likely to be more effective at suppressing an outbreak caused by a long-distance dispersed pathogen than would delayed treatment of a larger area. The scaling relationships we detail and the associated consequences for disease control may be broadly applicable to plant and animal pathogens characterized by non-exponentially bound, fat-tailed dispersal gradients.
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