Lower limb amputees experience gait impairments, in part due to limitations of prosthetic limbs and the lack of a functioning biarticular gastrocnemius (GAS) muscle. Energy storing prosthetic feet ...restore the function of the soleus, but not GAS. We propose a transtibial prosthesis that implements a spring mechanism to replicate the GAS. A prototype Biarticular Prosthesis (BP) was tested on seven participants with unilateral transtibial amputation. Participants walked on an instrumented treadmill with motion capture, first using their prescribed prosthesis, then with the BP in four different spring stiffness conditions. A custom OpenSim musculoskeletal model, including the BP, was used to estimate kinematics, joint torques, and muscle forces. Kinematic symmetry was evaluated by comparing the amputated and intact angles of the ankle, knee, and hip. The BP knee and ankle torques were compared to the intact GAS. Finally, work done by the BP spring was calculated at the ankle and knee. There were no significant differences between conditions in kinematic symmetry, indicating that the BP performs similarly to prescribed prostheses. When comparing the BP torques to intact GAS, higher spring stiffness better approximated peak GAS torques, but those peaks occurred earlier in the gait cycle. The BP spring did positive work on the knee joint and negative work on the ankle joint, and this work increased as BP spring stiffness increased. The BP has the potential to improve amputee gait compensations associated with the lack of biarticular GAS function, which may reduce their walking effort and improve quality of life.
Neural tube closure is a critical early step in central nervous system development that requires precise control of metabolism to ensure proper cellular proliferation and differentiation. ...Dysregulation of glucose metabolism during pregnancy has been associated with neural tube closure defects (NTDs) in humans suggesting that the developing neuroepithelium is particularly sensitive to metabolic changes. However, it remains unclear how metabolic pathways are regulated during neurulation. Here, we used single-cell mRNA-sequencing to analyze expression of genes involved in metabolism of carbon, fats, vitamins, and antioxidants during neurulation in mice and identify a coupling of glycolysis and cellular proliferation to ensure proper neural tube closure. Using loss of
as a genetic model of cranial NTD, we identify misregulated metabolic pathways and find a significant upregulation of glycolysis genes in embryos with NTD. These findings were validated using mass spectrometry-based metabolite profiling, which identified increased glycolytic and decreased lipid metabolites, consistent with a rewiring of central carbon traffic following loss of
. Predicted
targets
,
, and
are significantly upregulated upon NTD resulting in increased glycolytic flux, a shortened cell cycle, and increased proliferation. Our findings establish a critical role for
in coordinating the metabolic landscape of neural tube closure.
This paper describes the development, properties, and evaluation of a musculoskeletal model that reflects the anatomical and prosthetic properties of a transtibial amputee using OpenSim. Average ...passive prosthesis properties were used to develop CAD models of a socket, pylon, and foot to replace the lower leg. Additional degrees of freedom (DOF) were included in each joint of the prosthesis for potential use in a range of research areas, such as socket torque and socket pistoning. The ankle has three DOFs to provide further generality to the model. Seven transtibial amputee subjects were recruited for this study. 3 D motion capture, ground reaction force, and electromyographic (EMG) data were collected while participants wore their prescribed prosthesis, and then a passive prototype prosthesis instrumented with a 6-DOF load cell in series with the pylon. The model's estimates of the ankle, knee, and hip kinematics comparable to previous studies. The load cell provided an independent experimental measure of ankle joint torque, which was compared to inverse dynamics results from the model and showed a 7.7% mean absolute error. EMG data and muscle outputs from OpenSim's Static Optimization tool were qualitatively compared and showed reasonable agreement. Further improvements to the muscle characteristics or prosthesis-specific foot models may be necessary to better characterize individual amputee gait. The model is open-source and available at (
https://simtk.org/projects/biartprosthesis
) for other researchers to use to advance our understanding and amputee gait and assist with the development of new lower limb prostheses.
Abstract Late gestation heat stress in dairy cows has been shown to negatively affect offspring growth and development. In utero heat stressed calves have altered small intestine morphology and an ...impaired ability to absorb colostral immunoglobulin G (IgG). Thus, the objective of this study was to characterize potential cellular and molecular alterations in the small intestine of neonatal in utero heat stressed calves. In the last ~56 d of gestation pregnant dams were either heat stressed (shade; n = 41) or cooled (shade, fans, soakers; n = 41) resulting in heifers that were in utero heat stressed (IUHS, n = 15) or in utero cooled (IUCL, n = 15). Heifers were fed 3.78 L of high-quality colostrum within 2 h of birth. Apparent efficiency of absorption (AEA) of IgG was calculated by measuring IgG content fed in colostrum and in 24 h serum. Within 4.6 ± 2.3 h of birth a subset of calves (n = 8/treatment) not fed colostrum were euthanized to collect samples from the ileum. Tissue for histological analysis was placed in 10% neutral buffered formalin before being dehydrated, embedded in paraffin, cut into 5 μm thicknesses, and mounted to glass slides. The TUNEL method was used to identify apoptotic cells using the Keyence BZ-X800 Microscope. Tissue for gene expression analysis was snap-frozen and kept at -80°C before RNA extraction and cDNA synthesis. The transcript abundance of endosomal (FCGRT, DAB2, MAMDC4), tight junction (ZO1, ZO2, ZO3, OCLN, CLDN1), and heat shock (HSP90, HSF1) related genes were measured by qPCR using the CFX96 Real-Time PCR detection System (BIO-RAD). Data were analyzed using PROC MIXED or PROC GLIMMIX depending on the response variable. TUNEL results are expressed as the proportion of positive cells to total cells. Quantitative PCR data were analyzed by assessing the estimates of the model relative to the geometric mean of 3 reference genes (ACTB, GADPH, RSP9; ΔΔCT). The concentration of colostrum IgG fed to calves was not different (136.1 vs. 122.5 g/L; IUHS vs. IUCL, respectively; P = 0.32), but AEA of IgG was reduced in IUHS relative to IUCL calves (23.5 vs. 33.3%; P < 0.01). The proportion of apoptotic cells within the villi of the ileum was increased in IUHS calves compared with IUCL (2.11 vs. 1.57%; P < 0.01). Ileum gene transcript abundance of DAB2 and MAMDC4 were increased (P < 0.01), while FCGRT transcripts tended to increase in IUHS calves (P = 0.08). All tight junction and heat shock-related gene transcripts were increased within the ileum of IUHS calves (P ≤ 0.02) with the exceptions of CLDN1 and HSP90, which were not different between treatments (P ≥ 0.22).These results suggest that exposure to heat stress in utero impact small intestine integrity after birth and affect key IgG transporters, providing insight into underlying mechanisms responsible for reduced IgG absorption in IUHS calves.
Parent-reported influenza vaccination history may be valuable clinically and in influenza vaccine effectiveness (VE) studies. Few studies have assessed the validity of parental report among ...hospitalized children.
Parents of 2597 hospitalized children 6 months-17 years old were interviewed from November 1, 2015 to June 30, 2016, regarding their child's sociodemographic and influenza vaccination history. Parent-reported 2015-2016 influenza vaccination history was compared with documented vaccination records (considered the gold standard for analysis) obtained from medical records, immunization information systems, and providers. Multivariable logistic regression analyses were conducted to determine potential factors associated with discordance between the 2 sources of vaccination history. Using a test-negative design, we estimated VE using vaccination history obtained through parental report and documented records.
According to parental report, 1718 (66%) children received the 2015-2016 influenza vaccine, and of those, 1432 (83%) had documentation of vaccine receipt. Percent agreement was 87%, with a sensitivity of 96% (95% confidence interval CI, 95%-97%) and a specificity of 74% (95% CI, 72%-77%). In the multivariable logistic regression, study site and child's age 5-8 years were significant predictors of discordance. Adjusted VE among children who received ≥1 dose of the 2015-2016 influenza vaccine per parental report was 61% (95% CI, 43%-74%), whereas VE using documented records was 55% (95% CI, 33%-69%).
Parental report of influenza vaccination was sensitive but not as specific compared with documented records. However, VE against influenza-associated hospitalizations using either source of vaccination history did not differ substantially. Parental report is valuable for timely influenza VE studies.
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