Enhanced cortical reperfusion protects coagulation factor XII-deficient mice from ischemic stroke as revealed by high-field MRI

Intrinsic coagulation factor XII deficient (FXII^?/?) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla.Cerebral ischemia was induced by either transient (60 min) or permanent occlusion of the middle cerebral artery (t/pMCAO). 10 FXII^?/? mice underwent t- , 10 FXII^?/? mice p- and 10 Wildtype (Wt) mice tMCAO. Cerebral blood flow (CBF), diffusion-weighted-imaging (DWI) and T2-relaxometry were measured at 2 h and 24 h after MCAO. Outcome measures were evaluated after motion correction and normalization to atlas space. 2 h after tMCAO CBF reduction was similar in FXII^?/? and Wt mice extending over cortical (CBF (ml/100 g/min) 33.6 ± 6.9 vs. 35.3 ± 4.6, p = 0.42) and subcortical regions (25.7 ± 4.5 vs. 31.6 ± 4.0, p = 0.17). At 24 h, recovery of cortical CBF by +36% was observed only in tMCAO FXII^?/? mice contrasting a further decrease of – 30% in Wt mice after tMCAO (p = 0.02, F_(1,18) = 6.24). In FXII^?/? mice in which patency of the MCA was not restored (pMCAO) a further decrease of ? 75% was observed. Cortical reperfusion in tMCAO FXII^?/? mice was related to a lower risk of infarction of 59% vs. 93% in Wt mice (p = 0.04). Subcortical CBF was similarly decreased in both tMCAO groups (Wt and FXII^?/?) relating to a similar risk of infarction of 89% (Wt) vs. 99% (FXII^?/?, p = 0.17).Deficiency of FXII allows neocortical reperfusion after tMCAO and rescues brain tissue by this mechanism. This study supports the concept of FXII as a promising new target for stroke prevention and therapy.     

Persistent and automatic intraoperative 3D digitization of surfaces under dynamic magnifications of an operating microscope

One of the major challenges impeding advancement in image-guided surgical (IGS) systems is the soft-tissue deformation during surgical procedures. These deformations reduce the utility of the patient’s preoperative images and may produce inaccuracies in the application of preoperative surgical plans. Solutions to compensate for the tissue deformations include the acquisition of intraoperative tomographic images of the whole organ for direct displacement measurement and techniques that combines intraoperative organ surface measurements with computational biomechanical models to predict subsurface displacements. The later solution has the advantage of being less expensive and amenable to surgical workflow. Several modalities such as textured laser scanners, conoscopic holography, and stereo-pair cameras have been proposed for the intraoperative 3D estimation of organ surfaces to drive patient-specific biomechanical models for the intraoperative update of preoperative images. Though each modality has its respective advantages and disadvantages, stereo-pair camera approaches used within a standard operating microscope is the focus of this article. A new method that permits the automatic and near real-time estimation of 3D surfaces (at 1 Hz) under varying magnifications of the operating microscope is proposed. This method has been evaluated on a CAD phantom object and on full-length neurosurgery video sequences (∼1 h) acquired intraoperatively by the proposed stereovision system. To the best of our knowledge, this type of validation study on full-length brain tumor surgery videos has not been done before. The method for estimating the unknown magnification factor of the operating microscope achieves accuracy within 0.02 of the theoretical value on a CAD phantom and within 0.06 on 4 clinical videos of the entire brain tumor surgery. When compared to a laser range scanner, the proposed method for reconstructing 3D surfaces intraoperatively achieves root mean square errors (surface-to-surface distance) in the 0.28–0.81 mm range on the phantom object and in the 0.54–1.35 mm range on 4 clinical cases. The digitization accuracy of the presented stereovision methods indicate that the operating microscope can be used to deliver the persistent intraoperative input required by computational biomechanical models to update the patient’s preoperative images and facilitate active surgical guidance.     

Increased internal femoral torsion can be regarded as a risk factor for patellar instability — A biomechanical study

BackgroundIncreased internal femoral torsion is regarded as a risk factor for patellar instability. Biomechanical investigations confirming this hypothesis are missing.MethodsEight fresh-frozen cadaver knees were tested on a specially designed simulator. Patellar motion and patellofemoral pressure were evaluated for 0°, 10°, and 20° of increased internal and external femoral torsion with native and with transected medial patellofemoral ligaments used to simulate patellar instability. A regression analysis was used for statistical analysis.FindingsIn native medial patellofemoral ligaments, there were no significant changes in mean or peak pressures for any torsional states (P ≥ 0.07). At 20° increased internal femoral torsion, there was a significant center of force shift towards the lateral side (P = 0.01). Patellar shift was directed laterally at low knee flexion angles up to 30°. Lateral patellar tilt increased significantly at 10° and 20° of increased internal femoral torsion (P ≤ 0.004). In transected medial patellofemoral ligaments, mean pressure (P ≤ 0.005) and peak pressure (P ≤ 0.02) decreased significantly for all torsional states. There was a significantly greater lateral center of force shift with increased internal femoral torsion (P ≤ 0.04). Lateral patellar tilt increased significantly (P < 0.001). Patellar shift did not change significantly with increased internal femoral torsion (P ≥ 0.30).InterpretationIn a native medial patellofemoral ligament, 20° of increased internal femoral torsion can be regarded as a significant risk factor for patellar instability. With an insufficient medial patellofemoral ligament, 10° of increased internal femoral torsion already represents a significant risk factor.     

Perceived Success in Addressing End-of-Life Care Needs of Low-Income Elders and Their Families: What Has Family Conflict Got to Do With It?

The purpose of this study was to examine the predictors of perceived success in addressing the end-of-life care needs of low-income older adults and their family members. Perceived success is defined as the clinician’s subjective assessment of the extent to which end-of-life care needs of the patient and family have been met by the interdisciplinary team. The results are drawn from a larger longitudinal multimethod case study designed to understand how end-of-life care is provided to a diverse group of frail elders in an innovative, fully “integrated,” managed care program. Data were generated from 120 social work surveys detailing care experiences and outcomes particular to 120 elder deaths. Significant predictors of perceived success for addressing patient needs included patient care needs (β = 0.17, P ≤ 0.05), race (β = 0.19, P ≤ 0.05), patient preferences elicited (β = 0.29, P ≤ 0.01) and honored (β = 0.20, P ≤ 0.05), and family conflict (β = ?0.24, P ≤ 0.01). Significant predictors of perceived success for addressing family needs included family care needs (β = 0.30, P ≤ 0.001), team and administrative resources (β = 0.19, P ≤ 0.01), patient preferences honored (β = 0.16, P ≤ 0.05), quality of relationship with patient (β = 0.27, P ≤ 0.001) and family (β = 0.23, P ≤ 0.01), and family conflict (β = ?0.31, P ≤ 0.001). This study provides preliminary evidence of differential correlates and predictors of perceived success for addressing patient and family needs, highlighting the detrimental influence of family conflict. Future research is needed to better understand the kinds of assessment and intervention protocols that might prevent or ameliorate conflict and enhance structures and process-of-care variables to facilitate more successful outcomes.     

A PET [18F]altanserin study of 5-HT2A receptor binding in the human brain and responses to painful heat stimulation

There is a large body of evidence that serotonin [5-hydroxytryptamine (5-HT)] plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) to study the relationship between baseline 5-HT_2A binding in the brain and responses to noxious heat stimulation in a group of young healthy volunteers. Twenty-one healthy subjects underwent PET scanning with the 5-HT_2A antagonist, [¹⁸F]altanserin. In addition, participants underwent a battery of pain tests using noxious heat stimulation to assess pain threshold, pain tolerance and response to short-lasting phasic and long-lasting (7-minute) tonic painful stimulation. Significant positive correlations were found between tonic pain ratings and [¹⁸F]altanserin binding in orbitofrontal (r = 0.66; p = 0.005), medial inferior frontal (r = 0.60; p = 0.014), primary sensory–motor (r = 0.61; p = 0.012) and posterior cingulate (r = 0.63; p = 0.009) cortices. In contrast, measures of regional [¹⁸F]altanserin binding did not correlate with pain threshold, pain tolerance, or suprathreshold phasic pain responses. These data suggest that cortical 5-HT_2A receptor availability co-varies with responses to tonic pain. The correlation between [¹⁸F]altanserin binding in prefrontal cortex and tonic pain suggests a possible role of this brain region in the modulation and/or cognitive-evaluative appreciation of pain.     

Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates

Optimal results in the direct brain delivery of brain therapeutics such as growth factors or viral vector into primate brain depend on reproducible distribution throughout the target region. In the present study, we retrospectively analyzed MRI of 25 convection-enhanced delivery (CED) infusions with MRI contrast into the putamen of non-human primates (NHP). Infused volume (V_i) was compared to total volume of distribution (V_d) versus V_d within the target putamen. Excellent distribution of contrast agent within the putamen was obtained in eight cases that were used to define an optimal target volume or “green” zone. Partial or poor distribution with leakage into adjacent anatomical structures was noted in 17 cases, defining “blue” and “red” zones, respectively. Quantitative containment (99 ± 1%) of infused gadoteridol within the putamen was obtained when the cannula was placed in the green zone, 87 ± 3% in the blue zone and 49 ± 0.05% in the red zone. These results were used to determine a set of 3D stereotactic coordinates that define an optimal site for putaminal infusions in NHP and human putamen. We conclude that cannula placement and definition of optimal (green zone) stereotactic coordinates have important implications in ensuring effective delivery of therapeutics into the putamen utilizing routine stereotactic MRI localization procedures and should be considered when local therapies such as gene transfer or protein administration are being translated into clinical therapy.     

Lower limb alignment and laxity measures before,during and after total knee arthroplasty: A prospective cohort study

BackgroundThis study compared knee alignment and laxity in patients before, during and after total knee arthroplasty, using methodologically similar procedures, with an aim to help inform pre-operative planning.MethodsEighteen male and 13 female patients were recruited, mean age 66 years (51–82) and mean body mass index of 33 (23–43). All were assessed pre- and postoperatively using a non-invasive infrared position capture system and all underwent total knee arthroplasty using a navigation system. Knee kinematic data were collected and comparisons made between preoperative clinical and intraoperative measurements for osteoarthritic knees, and between postoperative clinical and intraoperative measurements for prosthetic knees.FindingsThere was no difference in unstressed coronal mechanical femoral-tibial angles for either osteoarthritic or prosthetic knees. However, for sagittal alignment the knees were in greater extension intraoperatively (osteoarthritic 5.2° p < 0.001, prosthetic 7.2° p < 0.001). For osteoarthritic knees, both varus and valgus stress manoeuvres had greater angular displacements intraoperatively by a mean value of 1.5° for varus (p = 0.002) and 1.6° for valgus (p < 0.001). For prosthetic knees, only valgus angular displacement was greater intraoperatively (0.9°, p = 0.002).InterpretationSurgeons performing total knee arthroplasties should be aware of potential differences in alignment and laxity measured under different conditions to facilitate more accurate operative planning and follow-up.     

Cerebral oximetry as a biomarker of postoperative delirium in cardiac surgery patients

PurposeA promising monitoring strategy for delirium is the use of cerebral oximetry, but its validity during delirium is unknown. We assessed the relationship between oximetry and delirium. We hypothesized that as cerebral oximetry values increased, delirium would resorb.Materials and methodsAn observational study was conducted with 30 consecutive adults with delirium after cardiac surgery. Oximetry, delirium assessments, and clinical data were collected for 3 consecutive days after delirium onset. Oximetry was obtained using near-infrared spectroscopy. Delirium was assessed using diagnosis, occurrence (Confusion Assessment Method-ICU), and severity scales (Delirium Index).ResultsAll patients presented delirium at entry. The mean oximetry value decreased from 66.4 ± 6.7 (mean ± SD) to 50.8 ± 6.8 on the first day after delirium onset and increased in patients whose delirium resorbed over the 3 days. The relationship between oximetry, delirium diagnosis, and severity was analyzed with a marginal model and linear mixed models. Cerebral oximetry was related to delirium diagnosis (P ≤ .0001) and severity (P ≤ .0001).ConclusionThis study highlighted the links between increased cerebral oximetry values and delirium resorption. Oximetry values may be useful in monitoring delirium progression, thus assisting in the management of this complicated condition.     

Harmony as a convergence attractor that minimizes the energy expenditure and variability in physiological gait and the loss of harmony in cerebellar ataxia

BackgroundThe harmony of the human gait was recently found to be related to the golden ratio value (ϕ). The ratio between the duration of the stance and that of the swing phases of a gait cycle was in fact found to be close to ϕ, which implies that, because of the fractal property of autosimilarity of that number, the gait ratios stride/stance, stance/swing, swing/double support, were not significantly different from one another. We studied a group of patients with cerebellar ataxia to investigate how the differences between their gait ratios and the golden ratio are related to efficiency and stability of their gait, assessed by energy expenditure and stride-to-stride variability, respectively.MethodsThe gait of 28 patients who were affected by degenerative cerebellar ataxia and of 28 healthy controls was studied using a stereophotogrammetric system. The above mentioned gait ratios, the energy expenditure estimated using the pelvis reconstructed method and the gait variability in terms of the stride length were computed, and their relationships were analyzed. Matching procedures have also been used to avoid multicollinearity biases.FindingsThe gait ratio values of the patients were farther from the controls (and hence from ϕ), even in speed matched conditions (P = 0.011, Cohen's D = 0.76), but not when the variability and energy expenditure were matched between the two groups (Cohen's D = 0.49). In patients with cerebellar ataxia, the farther the stance-swing ratio was from ϕ, the larger the total mechanical work (R²_adj = 0.64). Further, a significant positive correlation was observed between the difference of the gait ratio from the golden ratio and the severity of the disease (R = 0.421, P = 0.026).InterpretationHarmony of gait appears to be a benchmark of physiological gait leading to physiological energy recovery and gait reliability. Neurorehabilitation of patients with ataxia might benefit from the restoration of harmony of their locomotor patterns.     

Effect of imbalance and intracluster correlation coefficient in cluster randomization trials with binary outcomes when the available number of clusters is fixed in advance

In some cluster randomization trials, the number of clusters cannot exceed a specified maximum value due to cost constraints or other practical reasons. Donner and Klar [Donner A, and Klar N. Design and analysis of cluster randomization trials in health research. Oxford University Press 2000] provided the sample size formula for the number of subjects required per cluster when the number of clusters cannot exceed a specified maximum value. The sample size formula of Donner and Klar assumes that the number of subjects is the same in each cluster. In practical situations, the number of subjects may be different among clusters. We conducted simulation studies to investigate the effect of the cluster size variability (κ) and the intracluster correlation coefficient (ρ) on the power of the study in which the number of available clusters is fixed in advance. For the balanced case (κ = 1.0), i.e., equal cluster size among clusters, the sample size formula yielded empirical powers close to the nominal level even when the number of available clusters per group (k^?) is as small as 10. The sample size formula yielded empirical powers close to the nominal level when the number of available clusters per group (k^?) is at least 20 and the imbalance parameter (κ) is at least 0.8. Empirical powers were close to the nominal level when (ρ ≤ 0.02, κ ≥ 0.8, and k^? = 10) or (ρ ≤ 0.02, κ = 0.8, and k^? = 20).     

Effect of high-intensity exercise on cardiorespiratory fitness in stroke survivors: A systematic review and meta-analysis

BackgroundKnowledge of the optimal protocol and safety of particularly high-intensity exercise applied to individuals with stroke is lacking.ObjectiveThis systematic review and meta-analysis aimed to investigate the effect of high-intensity exercise on cardiorespiratory fitness in stroke survivors.MethodsWe performed a systematic electronic search for articles in MedLine via PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, and SPORTSDiscus up to April 1, 2019. Peak oxygen consumption (VO₂peak), 6-min walk test (6MWT), fastest 10-m walk test (10MWT), and adverse events were assessed. The standardized mean difference (SMD), weighted mean difference (WMD), and odds ratios (ORs) were used to compute the effect size, and subgroup analysis was conducted to test the consistency of results as well as sensitivity analysis to assess the robustness of the results. The quality of evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.ResultsWe included 17 studies (PEDro score ≥ 4) in the meta-analysis. Post-intervention, high-intensity exercise had a significant effect on peak oxygen uptake (VO₂peak; SMD = 0.56, P < 0.01, I² = 8%; WMD = 2.53 mL/kg/min; high quality of evidence) and 6MWT (SMD = 0.26, P < 0.01, I² = 40%; WMD = 17.08 m; moderate quality of evidence) but not fastest 10MWT (SMD = 0.33, P = 0.27, I² = 77%; WMD = 0.05 m/s; low quality of evidence). Subgroup analysis showed better effects of higher-intensity treadmill training (≥ 70% heart rate reserve/VO₂peak) for a longer duration (≥ 12 weeks) on VO₂peak and 6MWT in sub-acute or chronic stroke survivors. The high-intensity exercise and control groups did not differ in adverse events including falls [odds ratio (OR) 1.40, P = 0.35, I² = 11%; low quality of evidence], pain (OR 3.34, P = 0.09, I² = 0%; moderate quality of evidence), or skin injuries (OR 1.08, P = 0.90, I² = 0%; low quality of evidence).ConclusionsOur meta-analysis suggests that high-intensity exercise is beneficial for cardiorespiratory fitness in stroke survivors and might be safe as a novel intervention in cardiopulmonary rehabilitation after stroke.     

PAPP-A as a marker of increased long-term risk in patients with chest pain

ObjectivesLong-term risk stratification in patients presenting with acute coronary syndromes (ACS) is possible by measuring cardiac troponin (cTn). The present study examined whether PAPP-A measured in an emergency department (ED) chest pain population in association with conventional and novel high sensitivity cTn (hs-cTnI) assays can predict long-term mortality.MethodsIn 320 patients with cTn measurements the earliest heparinized plasma PAPP-A concentration after presentation was used for risk stratification for death by Kaplan–Meier and Cox analyses. Subgroup analyses using the earliest PAPP-A concentrations were also performed in a cohort of subjects with presentation cTnI ≤ 99th percentile but with significantly changing cardiac troponin concentrations as measured by the AccuTnI assay and the hs-cTnI assay (n = 45 and 120 subjects, respectively).ResultsSubjects with PAPP-A concentrations in the highest tertile were at higher risk for death (HR > 2.00; p ≤ 0.05 at 2 years) even after adjusting for cTnI at presentation. In the cohort with cTnI ≤ 99th percentile but with changing hs-cTnI concentrations, subjects in the top PAPP-A tertile had a higher probability for death (p = 0.02).ConclusionEarly measurement of PAPP-A may identify chest pain patients at higher risk for long-term death. Additional prospective ACS studies are required to fully elucidate PAPP-A's role.     

MP2RAGE,a self bias-field corrected sequence for improved segmentation and T1-mapping at high field

The large spatial inhomogeneity in transmit B₁ field (B₁⁺) observable in human MR images at high static magnetic fields (B₀) severely impairs image quality. To overcome this effect in brain T₁-weighted images, the MPRAGE sequence was modified to generate two different images at different inversion times, MP2RAGE. By combining the two images in a novel fashion, it was possible to create T₁-weigthed images where the result image was free of proton density contrast, T₂? contrast, reception bias field, and, to first order, transmit field inhomogeneity.MP2RAGE sequence parameters were optimized using Bloch equations to maximize contrast-to-noise ratio per unit of time between brain tissues and minimize the effect of B₁⁺ variations through space. Images of high anatomical quality and excellent brain tissue differentiation suitable for applications such as segmentation and voxel-based morphometry were obtained at 3 and 7 T.From such T₁-weighted images, acquired within 12 min, high-resolution 3D T₁ maps were routinely calculated at 7 T with sub-millimeter voxel resolution (0.65–0.85 mm isotropic). T₁ maps were validated in phantom experiments. In humans, the T₁ values obtained at 7 T were 1.15 ± 0.06 s for white matter (WM) and 1.92 ± 0.16 s for grey matter (GM), in good agreement with literature values obtained at lower spatial resolution. At 3 T, where whole-brain acquisitions with 1 mm isotropic voxels were acquired in 8 min, the T₁ values obtained (0.81 ± 0.03 s for WM and 1.35 ± 0.05 for GM) were once again found to be in very good agreement with values in the literature.     

Relative utility for hemispheric lateralization of different clinical fMRI activation tasks within a comprehensive language paradigm battery in brain tumor patients as assessed by both threshold-dependent and threshold-independent analysis methods

The aim of this study was to compare the relative effectiveness of 6 different commonly used language fMRI activation paradigms, including receptive and expressive, as well as semantic and phonological tasks, for hemispheric lateralization in brain tumor patients utilizing both threshold-dependent and threshold-independent approaches. We studied 46 right-handed patients with primary intra-axial brain tumors with BOLD fMRI on a 3-T MRI system. A linear fit of the laterality indices (LIs) as a function of the t-value (which varied from 2.0 to 6.5) was calculated and the slope (M) taken as measure of LI variability in the threshold-dependent LI approach; for the threshold-independent approach, the LIs were determined by comparing the integrated T-score weighted distributions of all positively task-correlated voxels of the left and the right hemispheric regions of interest. We demonstrated that silent word generation (SWG) and rhyming (R) were the two expressive tasks that provided the best hemispheric language lateralization in this group, based on concordant threshold-dependent and threshold-independent analyses. Furthermore, R (mean LI value = 61.91, M = 7.9 ± 1.5) had a higher mean LI value and was less threshold-dependent than SWG (mean LI = 52.97, M = 11.40 ± 0.64) for LI determination. SWG and R were able to provide effective language lateralization even in the subgroup of patients with lesions located in the left hemisphere and in the frontal or parietal lobes. The receptive language paradigms examined in this study (passive listening [PL], listening comprehension [LC], and reading comprehension [RC]) were less effective than SWG and R for language lateralization.     

Patterns of altered cortical perfusion and diminished subcortical integrity in posttraumatic stress disorder: An MRI study

Posttraumatic stress disorder (PTSD) accounts for a substantial proportion of casualties among surviving soldiers of the Iraq and Afghanistan wars. Currently, the assessment of PTSD is based exclusively on symptoms, making it difficult to obtain an accurate diagnosis. This study aimed to find potential imaging markers for PTSD using structural, perfusion, and diffusion magnetic resonance imaging (MRI) together. Seventeen male veterans with PTSD (45 ± 14 years old) and 15 age-matched male veterans without PTSD had measurements of regional cerebral blood flow (rCBF) using arterial spin labeling (ASL) perfusion MRI. A slightly larger group had also measurements of white matter integrity using diffusion tensor imaging (DTI) with computations of regional fractional anisotropy (FA). The same subjects also had structural MRI of the hippocampal subfields as reported recently (W. Zhen et al. Arch Gen Psych 2010;67(3):296–303). On ASL-MRI, subjects with PTSD had increased rCBF in primarily right parietal and superior temporal cortices. On DTI, subjects with PTSD had FA reduction in white matter regions of the prefrontal lobe, including areas near the anterior cingulate cortex and prefrontal cortex as well as in the posterior angular gyrus. In conclusion, PTSD is associated with a systematic pattern of physiological and structural abnormalities in predominantly frontal lobe and limbic brain regions. Structural, perfusion, and diffusion MRI together may provide a signature for a PTSD marker.     

Proatherogenic disturbances in lipoprotein profile,associated enzymes and transfer proteins in women with iron deficiency anaemia

ObjectiveTo characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients.Design and methodsTwenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A₂ (LpPLA₂) activities and plasma levels of oxidized-LDL were evaluated.ResultsTriglycerides were higher (median [range]) (1.0 [0.5–1.9] vs. 0.7 [0.5–1.5] mmol/L, p < 0.05) and HDL-C lower (mean ± SD) (1.3 ± 0.3 vs. 1.6 ± 0.4 mmol/L, p < 0.01) in the patients group. CETP (197 ± 29% vs. 151 ± 29% mL^? 1 h^? 1, p < 0.001), PON 1 (122 ± 17 vs. 140 ± 33 μmol mL^? 1 min^? 1, p < 0.05) and LpPLA₂ (9.6 ± 2.0 vs. 8.1 ± 1.7 μmol mL^? 1 h^? 1, p < 0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r = ? 0.35, p < 0.05), CETP (r =  ?  0.62, p < 0.001) and LpPLA₂ (r =  ?  0.34, p < 0.05), while ferritin was positively associated with HDL-C (r =  0.39, p < 0.05) and inversely with CETP (r =  ?  0.49, p < 0.005).ConclusionThe alterations in lipoprotein profile, CETP, PON 1 and LpPLA₂ activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.     

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O PET study

Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H₂¹⁵O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H₂¹⁵O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76.1 ± 25.2 before SCS to 40.6 ± 4.5 after SCS (mean ± SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS.     

Comparative analysis of posterior fusion constructs as treatments for middle and posterior column injuries: An in vitro biomechanical investigation

BackgroundTitanium pedicle screw–rod instrumentation is considered a standard treatment for spinal instability; however, the advantages of cobalt-chromium over titanium is generating interest in orthopedic practice. The aim of this study was to compare titanium versus cobalt–chromium rods in posterior fusion through in vitro biomechanical testing.MethodsPosterior and middle column injuries were simulated at L3–L5 in six cadaveric L1-S1 human spines and different pedicle screw constructs were implanted. Specimens were subjected to flexibility tests and range of motion, intradiscal pressure and axial rotation energy loss were statistically compared among five conditions: intact, titanium rods (with and without transverse connectors) and cobalt–chromium rods (with and without transverse connectors).FindingsAll fusion constructs significantly (P < 0.01) decreased range of motion in flexion–extension and lateral bending with respect to intact, but no significant differences (P > 0.05) were observed in axial rotation among all conditions. Intradiscal pressure significantly increased (P ≤ 0.01) after fusion, except for the cobalt–chrome conditions in extension (P ≥ 0.06), and no significant differences (P > 0.99) were found among fixation constructs. In terms of energy loss, differences became significant P ≤ 0.05 between the cobalt ? chrome with transverse connector condition with respect to the cobalt–chrome and titanium conditions.InterpretationThere is not enough evidence to support that the cobalt–chrome rods performed biomechanically different than the titanium rods. The inclusion of the transverse connector only increased stability for the cobalt–chromium construct in axial rotation.     

Cerebral ischemia-induced mitochondrial changes in a global ischemic rat model by AFM

Mitochondria play a central role in cell survival, and apoptotic cell death is associated with morphological changes in mitochondria. Quantification of the morphological and mechanical property changes in brain mitochondria is useful for evaluating the degree of ischemic injury and the neuroprotective effects of various drugs. This study was performed to investigate the changes in brain mitochondria in an 11-vessel occlusion ischemic model treated with magnesium sulfate (MgSO₄), utilizing atomic force microscopy (AFM). Rats were randomly divided into three groups consisting of sham (n = 6), global ischemia (GI, n = 6), and MgSO₄-treated global ischemia (MgSO₄, n = 6). The biophysical properties of brain mitochondria determined from AFM topographic images and adhesion force from force–distance measurements. The mean perimeter of ischemic mitochondria significantly increased to 2,396 ± 541 nm (vs. 1,006 ± 318 nm in control group, P < 0.001). The MgSO₄ treatment during global ischemia reduced the perimeter of ischemic mitochondria (1,127 ± 399 nm, P < 0.001). The other parameters including length, width and area were significantly different than the GI group. Besides, the adhesion force (23.2 ± 3.9 nN) of isolated mitochondria from the MgSO₄ group was close to normal levels (28.5 ± 2.5 nN), compared with that of ischemic ones (17.7 ± 3.3 nN, P < 0.001). To confirm the neuroprotective effects of MgSO₄, we performed Nissl staining. This study suggested that quantitative analysis of mitochondrial changes utilizing AFM could be effective for evaluating neuronal injury and drug effects.