Contact kinematics in total knee arthroplasty (TKA) has been shown to affect tibial component migration. However, previous studies correlating kinematic variables to implant migration were completed ...with older TKA designs. The goal of this study was to determine if there are associations between contact kinematics and tibial component migration for a cemented, bicruciate stabilized (BCS) TKA system.
A total of 54 knees implanted with a BCS TKA system were analyzed using radiostereometric analysis (RSA). Patients underwent RSA exams at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years post operation to measure tibial component migration. At 1 year, contact kinematics was evaluated during a quasi-static deep knee bend. Linear regression analyses were performed between kinematic variables and migration values.
Significant correlations were found between contact kinematics and tibial component migration. Excursion on the lateral condyle was the most consistent variable correlating with implant migration. Six patients had > 0.2 mm migrations from 1 to 2 years post operation indicating continuously migrating tibial components, and most had atypical contact kinematics.
Kinematics was shown to influence tibial component migration. Reduced lateral excursion, suggesting a more constrained lateral condyle, resulted in greater implant migration. The 6 patients who had continuously migrating tibial components had demographic factors that may limit the ability to endure unintended force transmissions caused by abnormal kinematics. These results highlight the importance of restoring knee kinematics with this BCS TKA design to minimize improper force transmissions and resultant increased implant migrations.
Organismal metabolic rate, a fundamental metric in biology, demonstrates an allometric scaling relationship with body size. Fractal-like vascular distribution networks of biological systems are ...proposed to underlie metabolic rate allometric scaling laws from individual organisms to cells, mitochondria, and enzymes. Tissue-specific metabolic scaling is notably absent from this paradigm. In the current study, metabolic scaling relationships of hearts and brains with body size were examined by improving on a high-throughput whole-organ oxygen consumption rate (OCR) analysis method in five biomedically and environmentally relevant teleost model species. Tissue-specific metabolic scaling was compared with organismal routine metabolism (RMO2), which was measured using whole organismal respirometry. Basal heart OCR and organismal RMO2 scaled identically with body mass in a species-specific fashion across all five species tested. However, organismal maximum metabolic rates (MMO2) and pharmacologically-induced maximum cardiac metabolic rates in zebrafish Danio rerio did not show a similar relationship with body mass. Brain metabolic rates did not scale with body size. The identical allometric scaling of heart and organismal metabolic rates with body size suggests that hearts, the power generator of an organism's vascular distribution network, might be crucial in determining teleost metabolic rate scaling under routine conditions. Furthermore, these findings indicate the possibility of measuring heart OCR utilizing the high-throughput approach presented here as a proxy for organismal metabolic rate-a useful metric in characterizing organismal fitness. In addition to heart and brain OCR, the current approach was also used to measure whole liver OCR, partition cardiac mitochondrial bioenergetic parameters using pharmacological agents, and estimate heart and brain glycolytic rates. This high-throughput whole-organ bioenergetic analysis method has important applications in toxicology, evolutionary physiology, and biomedical sciences, particularly in the context of investigating pathogenesis of mitochondrial diseases.
Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma and have been used for the treatment of primary immunodeficiency disorders for more than 24 years. Shortly after their ...introduction, IVIG products were also found to be effective in the treatment of autoimmune and inflammatory disorders. Over the past 2 decades, the list of diseases where IVIG has a demonstrable beneficial effect has grown rapidly. These include Kawasaki disease, Guillain‐Barre syndrome, myasthenia gravis, dermatomyositis and demyelinating polyneuropathy. Recently, we have described a beneficial effect on the reduction of anti‐HLA antibodies with subsequent improvement in transplantation of highly HLA‐sensitized patients as well as a potent anti‐inflammatory effect that is beneficial in the treatment of antibody‐mediated rejection (AMR). These advancements have enabled transplantation of patients previously considered untransplantable. These studies and relevant mechanism(s) of action will be discussed here.
Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average connectivity of several ...interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells, and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type-specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together, these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.
It is well known that changes in the starting powder can have a significant impact on the laser powder bed fusion process and subsequent part performance. Relationships between the powder particle ...size distribution and powder performance such as flowability and spreadability are generally known; however, links to part performance are not fully established. This study attempts to more precisely isolate the effect of particle size by using three customized batches of 17-4 PH stainless steel powders with small shifts in particle size distributions having non-intersecting cumulative size distributions, designated as Fine, Medium, and Coarse. It is found that the Fine powder has the worst overall powder performance with poor flow and raking during spreading while the Coarse powder has the best overall flow. Despite these differences in powder performance, the microstructures (i.e., porosity, grain size, phase, and crystallographic texture) of the built parts using the same process parameters are largely the same. Furthermore, the Medium powder produced parts with the highest mechanical properties (i.e., hardness and tensile strength) while the Fine and Coarse powders produced parts with effectively identical mechanical properties. Parts with good static mechanical properties can be produced from powders with a wide range of powder performance.
Display omitted
•Moderate changes in the size lead to significant changes in powder performance.•Static mechanical properties are robust against moderate changes in particle size.•Better control of powder is required to precisely know the effects of particle size.
Ecosystem metabolism in a stratified lake Staehr, Peter A.; Christensen, Jesper P. A.; Batt, Ryan D. ...
Limnology and oceanography,
September 2012, Letnik:
57, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Seasonal changes in rates of gross primary production (GPP), net ecosystem production (NEP), and respiration (R) were determined from frequent automated profiles of dissolved oxygen (DO) and ...temperature in a clear-water polymictic lake. Metabolic rate calculations were made using a method that integrates rates across the entire depth profile and includes DO exchange between depth layers driven by mixed-layer deepening and eddy diffusivity. During full mixing, NEP was close to zero throughout the water column, and GPP and R were reduced 2–10 times compared to stratified periods. When present, the metalimnion contributed 21% and 27% to whole-lake areal rates of GPP and R, respectively. Net autotrophy prevailed in the epilimnion (NEP = 11 ± 14 mmol O₂ m−3 d−1; mean ± SD) compared to balanced production in the metalimnion (NEP = 2 ± 19 mmol O₂m−3 d−1) and net heterotrophic conditions in hypolimnic waters (NEP = −15 ± 24 mmol O₂m−3 d−1). Positive NEP occurred in the metalimnion during periods when the photic depth extended below the mixed-layer depth. Although the single-sonde method estimated higher areal GPP (19%) and R (14%) compared to the two depth-integrated approaches, differences were not significant. During stratification, daily variability in epilimnetic DO was dominated by metabolism (46%) and air–water gas exchange (44%). Fluxes related to mixed-layer deepening dominated in meta- and hypolimnic waters (49% and 64%), while eddy diffusion (1% and 14%) was less important. Although air–water gas exchange rates differed among the three formulations of gas-transfer velocity, this had no significant effect on metabolic rates.
The utility of ultrasound imaging and therapy with microbubbles may be greatly enhanced by determining their impulse-response dynamics as a function of size and composition. Prior methods for ...microbubble characterization utilizing high-speed cameras, acoustic transducers and laser-based techniques typically scan a limited frequency range. Here, we report on the use of a novel photoacoustic technique to measure the impulse response of single microbubbles. Individual microbubbles are driven with a broadband photoacoustic wave generated by a nanosecond-pulse laser illuminating an optical absorber. The resulting microbubble oscillations were detected by following transmission of a second laser as it passes twice through the microbubble. The system could even resolve oscillations resulting from a single-shot. As a proof-of-concept study, the size-dependent, linear impulse response of lipid-coated microbubbles was characterized using this technique. This unique method of microbubble characterization with exceptional spatiotemporal resolution opens new avenues for capturing and analyzing microbubble system dynamics.
Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to ...suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy.
Patients with common variable immunodeficiency associated with autoimmune cytopenia (CVID+AIC) generate few isotype-switched B cells with severely decreased frequencies of somatic hypermutations ...(SHMs), but their underlying molecular defects remain poorly characterized. We identified a CVID+AIC patient who displays a rare homozygous missense M466V mutation in β-catenin-like protein 1 (CTNNBL1). Because CTNNBL1 binds activation-induced cytidine deaminase (AID) that catalyzes SHM, we tested AID interactions with the CTNNBL1 M466V variant. We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. As a consequence, the scarce IgG+ memory B cells from the CTNNBL1 466V/V patient showed a low SHM frequency that averaged 6.7 mutations compared with about 18 mutations per clone in healthy-donor counterparts. In addition, CTNNBL1 466V/V Ramos B cells displayed a decreased incidence of SHM that was reduced by half compared with parental WT Ramos B cells, demonstrating that the CTNNBL1 M466V mutation is responsible for defective SHM induction. We conclude that CTNNBL1 plays an important role in regulating AID-dependent antibody diversification in humans.
Dysregulated immune responses are essential underlying causes of a plethora of pathologies including cancer, autoimmunity, and immunodeficiency. We here investigated 4 patients from unrelated ...families presenting with immunodeficiency, autoimmunity, and malignancy. We identified 4 distinct homozygous mutations in TNFRSF9 encoding the tumor necrosis factor receptor superfamily member CD137/4-1BB, leading to reduced, or loss of, protein expression. Lymphocytic responses crucial for immune surveillance, including activation, proliferation, and differentiation, were impaired. Genetic reconstitution of CD137 reversed these defects. CD137 deficiency is a novel inborn error of human immunity characterized by lymphocytic defects with early-onset Epstein-Barr virus (EBV)-associated lymphoma. Our findings elucidate a functional role and relevance of CD137 in human immune homeostasis and antitumor responses.
•CD137 deficiency is a novel inborn error of immunity with immune dysregulation and EBV-associated lymphomagenesis.•Our study highlights the key role of CD137 for immune homeostasis with relevance to immunodeficiency and cancer immunotherapy.
Display omitted
PDF
