Identification of predictive MRI and functional biomarkers in a pediatric piglet traumatic brain injury model

Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments; however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP: A2015 11-001) on December 22, 2015.     

Integration of light scattering with machine learning for label free cell detection

Light scattering has been used for label-free cell detection. The angular light scattering patterns from the cells are unique to them based on the cell size, nucleus size, number of mitochondria, and cell surface roughness. The patterns collected from the cells can then be classified based on different image characteristics. We have also developed a machine learning (ML) method to classify these cell light scattering patterns. As a case study we have used this light scattering technique integrated with the machine learning to analyze staurosporine-treated SH-SY5Y neuroblastoma cells and compare them to non-treated control cells. Experimental results show that the ML technique can provide a classification accuracy (treated versus non-treated) of over 90%. The predicted percentage of the treated cells in a mixed solution is within 5% of the reference (ground-truth) value and the technique has the potential to be a viable method for real-time detection and diagnosis.     

A prospective study on survival in cancer patients with and without venous thromboembolism

Retrospective population-based studies showed that in cancer patients venous thromboembolism (VTE) is associated with reduced survival. Master Oncology is a multicenter study in patients with solid advanced cancer aimed at assessing (1) risk factors for VTE using a case–control design, and (2) survival in cases (patients with VTE) and controls (patients without VTE). Survival data were prospectively collected for at least 10 months. Overall, 237 cases and 339 controls were included in the analysis. The following factors were found to be associated with an increased risk of VTE: body mass index (BMI; OR 2.02; 95 % CI 1.31–3.12 for ≥26 vs. <23 kg/m²), ECOG score (OR 2.14; 95 % CI 1.47–3.11 for grade 1, and 3.32; 95 % CI 1.64–6.00 for grade 2–3, compared to grade 0) and recent diagnosis of cancer (OR 1.90; 95 % CI 1.33–2.71 for <12 vs. ≥12 months). After an average prospective observation of 8.3 months, 136 cases (57.4 %) and 127 controls (37.5 %) died with a median survival of 8.7 (95 % CI 7.5–10.9) and 14.3 months (95 % CI 12.2–18.7), respectively, (Wilcoxon = 27.72, p < 0.001; multivariate hazard ratio 1.55; 95 % CI 1.21–2.00). Median survival time was reduced for both patients with symptomatic (Wilcoxon = 35.22, p < 0.001) and asymptomatic VTE (Wilcoxon = 4.63, p = 0.031). Patients with advanced solid cancer, high BMI, high ECOG score, and recent diagnosis of cancer are associated with an increased risk for VTE. Patients with both symptomatic and asymptomatic VTE have a reduced survival compared to those without VTE.     

Glutathionyl hemoglobin is elevated in iron deficiency anemia

There are few good biomarkers of iron deficiency anemia (IDA). Since IDA patients have evidence for increased oxidative stress, we used mass spectrometry (MS) [i.e. matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization] to identify novel biomarkers. Using MALDI-MS, the following oxidative modifications of hemoglobin with the following mass-to-charge ratios were identified: 1,087.5 (α32-40), 1,545.7 (α17-31), 1,290.0 (β31-40) and 2,076.1 (β41-59). On electrospray ionization MS, the IDA patients had significantly elevated glutathionyl hemoglobin (GSHb) compared with the controls (16.9 ± 9.6 vs. 7.7 ± 3.7%; p = 0.002). GSHb levels correlated inversely with serum ferritin (Spearman rho -0.485; p = 0.003) and positively with serum transferrin receptor (0.460; p = 0.002). GSHb also demonstrated inverse correlations with hemoglobin (-0.512; p = 0.001), mean cell volume (-0.419; p = 0.026), serum iron (-0.446; p = 0.008) and transferrin saturation (-0.460; p = 0.008). For the first time, we show that GSHb is elevated in patients with IDA and has potential as a biomarker of this form of anemia.     

<Emphasis Type="Italic">PTEN</Emphasis>-mediated AKT activation contributes to the reduced apoptosis among Indian oral squamous cell carcinoma patients

Purpose  

The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established.     

Patterns of hand preference and unintentional injuries among Indian attempted hand switchers and hand non-switchers

This study examines the patterns of hand preference and unintentional injuries of attempted hand switchers and hand non-switchers. Data were collected from 3698 participants in Kharagpur, India, on measures of hand preference, hand switching, and unintentional injuries. The direction of left- or right-handedness was on the basis of hand used for the item “writing on paper” and the degree of handedness was based on the average score of remaining items in the handedness inventory. Results reveal that, among attempted hand-switchers, learned right-handers were not right-sided in hand continuum as the natural right-handers, but left-handers were left-sided as natural left-handers. With increasing age the learned right-handers become less right-sided and natural right-handers become more right-sided. Females (males) are found to be more right-handed than males (females) among learned right-handers (natural right-handers). On the direction of handedness, the learned right-handers have more than twice the risk of unintentional injuries than the natural right- and left-handers. On degree of handedness, the use of inconsistent left and both hands among natural left-handers, the use of inconsistent right and both hands among natural right-handers, and the use of weak right hand among learned right-handers increase their vulnerability to unintentional injuries. Any deviation from the genetic make-up in hand use elevates the risk of unintentional injuries, suggesting that one should not change the biological hand.     

Optimization of the position of the acetabulum in a ganz periacetabular osteotomy by finite element analysis

Periacetabular osteotomy (PAO) is a surgical procedure to correct acetabular orientation in developmental dysplasia of the hip (DDH). It changes the position of the acetabulum to increase femoral head coverage and distribute the contact pressure over the cartilage surface. The success of PAO depends significantly on the surgeon's experience. Using computed tomography data from patients with DDH, we developed a 3D finite element (FE) model to investigate the optimal position of the acetabulum following PAO. A virtual PAO was performed with the acetabulum rotated in increments from the original center edge (CE) angle. Contact area, contact pressure, and Von Mises stress in the femoral and pelvic cartilage were analyzed. Five dysplastic hips from four patients were modeled. Contact area, contact pressure, and Von Mises stress in the cartilage all varied according to the change of CE angle through virtual PAO. An optimal position could be achieved for the acetabulum that maximizes the contact area while minimizing the contact pressure and von Mises stress in the pelvic and femoral cartilage. The optimal position of the acetabulum was patient dependent and did not always correspond to what would be considered a “normal” CE angle. We demonstrated for the first time the interrelation of correction angle, contact area, and contact pressure between the pelvic and femoral cartilage in PAO surgery. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 472–479, 2013