Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.

Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically.

Anatomical parameters alter the biomechanical responses of adjacent segments following lumbar fusion surgery: Personalized poroelastic finite element modelling investigations.

Introduction: While the short-term post-operative outcome of lumbar fusion is satisfying for most patients, adjacent segment disease (ASD) can be prevalent in long-term clinical observations. It might be valuable to investigate if inherent geometrical differences among patients can significantly alter the biomechanics of adjacent levels post-surgery. This study aimed to utilize a validated geometrically personalized poroelastic finite element (FE) modeling technique to evaluate the alteration of biomechanical response in adjacent segments post-fusion. Methods: Thirty patients were categorized for evaluation in this study into two distinct groups [i.e., 1) non-ASD and 2) ASD patients] based on other long-term clinical follow-up investigations. To evaluate the time-dependent responses of the models subjected to cyclic loading, a daily cyclic loading scenario was applied to the FE models. Different rotational movements in different planes were superimposed using a 10 Nm moment after daily loading to compare the rotational motions with those at the beginning of cyclic loading. The biomechanical responses of the lumbosacral FE spine models in both groups were analyzed and compared before and after daily loading. Results: The achieved comparative errors between the FE results and clinical images were on average below 20% and 25% for pre-op and post-op models, respectively, which confirms the applicability of this predictive algorithm for rough pre-planning estimations. The results showed that the disc height loss and fluid loss were increased for the adjacent discs in post-op models after 16 h of cyclic loading. In addition, significant differences in disc height loss and fluid loss were observed between the patients who were in the non-ASD and ASD groups. Similarly, the increased stress and fiber strain in the annulus fibrosus (AF) was higher in the adjacent level of post-op models. However, the calculated stress and fiber strain values were significantly higher for patients with ASD. Discussion: Evaluating the biomechanical response of pre-op and post-op modeling in the non-ASD and ASD groups showed that the inherent geometric differences among patients cause significant variations in the estimated mechanical response. In conclusion, the results of the current study highlighted the effect of geometrical parameters (which may refer to the anatomical conditions or the induced modifications regarding surgical techniques) on time-dependent responses of lumbar spine biomechanics.

Use of biphasic calcium phosphate versus demineralized bone matrix: retrospective clinical and CT analysis of posterolateral fusion results.

PURPOSE: Bone graft extenders have been developed to prevent donor site morbidity associated with iliac crest bone graft, but few studies compared the efficacy of various substitutes. Our purpose was to determine fusion rate and clinical outcome in patients undergoing lumbar arthrodesis using demineralized bone matrix (DBM) and biphasic calcium phosphate (BCP). METHODS: Patients with degenerative spondylolisthesis undergoing one-level or two-level arthrodesis of lumbar spine were retrospectively reviewed. Two treatment groups placed either BCP or DBM, in addition to local autograft in lumbar posterolateral space. Three-dimensional CT exam and dynamic flexion-extension radiographs at postoperative 2-year were assessed for posterolateral fusion status and pain scale and Oswestry Disability Index (ODI) for clinical outcome. RESULTS: Of the 148 patients reviewed (including 23 in one- and 58 patients in two-level in BCP group, and 47 in one- and 20 patients in two-level in DBM group), no significant differences were found in terms of age, sex, BMI, smoking, diabetes, steroids, number of level fused, non-union rate or revision surgery between BCP and DBM groups. Significantly improved pain scale of back and leg and ODI were found in both groups postoperatively without group difference. We found a comparable fusion rate in one-level surgery (100% versus 93.6%) and a superior fusion rate of BCP group in two-level surgery (98.3% versus 80.0%, p = 0.01). CONCLUSION: Being a bone graft extender without osteoinductive property, with local autograft, BCP is comparable to DBM for one- and superior for two-level fusion. No significant difference was found in clinical outcomes.

Comparisons of Lumbar Muscle Performance Between Minimally-Invasive and Open Lumbar Fusion Surgery at 1-Year Follow-Up.

STUDY DESIGN: Prospective study. OBJECTIVE: Minimally-invasive lumbar fusion surgery (MIS) is a viable alternative to conventional open surgery (COS) for spinal disorders. Although MIS seems to be associated with less para-spinal muscle trauma, the actual back muscle performance after MIS and COS remain controversial. This study investigated post-operative para-spinal muscle performance, and the correlation between muscle dysfunction and clinical outcome. METHODS: In this prospective, non-randomized control study, 50 patients were enrolled and split into 2 groups: COS and MIS. We established a biomechanical model of the para-spinal muscle in the lumbar spine using electromyography (EMG) and specific muscle function tests. Functional outcomes were also reviewed and analyzed. All patients underwent EMG pre-operatively, and at 3 months and 1 year post-operatively. The para-spinal muscle performance was investigated by comparing the back muscle co-contraction ratio and the load transmission zone to the pre-operative data. RESULTS: Twenty-one patients in the COS group and 25 in the MIS group completed the study. Both groups showed a significant improved functional score. The abdominal and back muscle strengths were decreased post-operatively, and were then increased at 12 months post-operatively in both groups. During the perturbed balance task and static task, the MIS group exhibited a trend of recovery in comparison with the COS group. But, the back muscle performance at 12 months was poorer than the pre-op performance in both groups. CONCLUSIONS: There was no significant difference in clinical outcome and para-spinal muscle performance between groups. In both methods, the global muscle function had declined post-operatively.

Corrigendum: Biomechanical Investigation Between Rigid and Semirigid Posterolateral Fixation During Daily Activities: Geometrically Parametric Poroelastic Finite Element Analyses.

[This corrects the article DOI: 10.3389/fbioe.2021.646079.].

Biomechanical Investigation Between Rigid and Semirigid Posterolateral Fixation During Daily Activities: Geometrically Parametric Poroelastic Finite Element Analyses.

While spinal fusion using rigid rods remains the gold standard treatment modality for various lumbar degenerative conditions, its adverse effects, including accelerated adjacent segment disease (ASD), are well known. In order to better understand the performance of semirigid constructs using polyetheretherketone (PEEK) in fixation surgeries, the objective of this study was to analyze the biomechanical performance of PEEK versus Ti rods using a geometrically patient-specific poroelastic finite element (FE) analyses. Ten subject-specific preoperative models were developed, and the validity of the models was evaluated with previous studies. Furthermore, FE models of those lumbar spines were regenerated based on postoperation images for posterolateral fixation at the L4-L5 level. Biomechanical responses for instrumented and adjacent intervertebral discs (IVDs) were analyzed and compared subjected to static and cyclic loading. The preoperative model results were well comparable with previous FE studies. The PEEK construct demonstrated a slightly increased range of motion (ROM) at the instrumented level, but decreased ROM at adjacent levels, as compared with the Ti. However, no significant changes were detected during axial rotation. During cyclic loading, disc height loss, fluid loss, axial stress, and collagen fiber strain in the adjacent IVDs were higher for the Ti construct when compared with the intact and PEEK models. Increased ROM, experienced stress in AF, and fiber strain at adjacent levels were observed for the Ti rod group compared with the intact and PEEK rod group, which can indicate the risk of ASD for rigid fixation. Similar to the aforementioned pattern, disc height loss and fluid loss were significantly higher at adjacent levels in the Ti rod group after cycling loading which alter the fluid-solid interaction of the adjacent IVDs. This phenomenon debilitates the damping quality, which results in disc disability in absorbing stress. Such finding may suggest the advantage of using a semirigid fixation system to decrease the chance of ASD.

Comparison of paraspinal muscle degeneration and decompression effect between conventional open and minimal invasive approaches for posterior lumbar spine surgery.

Laminotomy and transforaminal lumbar interbody fusion (TLIF) is usually used to treat unstable spinal stenosis. Minimally invasive surgery (MIS) can cause less muscle injury than conventional open surgery (COS). The purpose of this study was to compare the degree of postoperative fatty degeneration in the paraspinal muscles and the spinal decompression between COS and MIS based on MRI. Forty-six patients received laminotomy and TLIF (21 COS, 25 MIS) from February 2016 to January 2017 were included in this study. Lumbar MRI was performed within 3 months before surgery and 1 year after surgery to compare muscle-fat-index (MFI) change of the paraspinal muscles and the dural sac cross-sectional area (DSCAS) change. The average MFI change at L2-S1 erector spinae muscle was significantly greater in the COS group (27.37 ± 21.37% vs. 14.13 ± 19.19%, P = 0.044). A significant MFI change difference between the COS and MIS group was also found in the erector spinae muscle at the caudal adjacent level (54.47 ± 37.95% vs. 23.60 ± 31.59%, P = 0.016). DSCSA improvement was significantly greater in the COS group (128.15 ± 39.83 mm2 vs. 78.15 ± 38.5 mm2, P = 0.0005). COS is associated with more prominent fatty degeneration of the paraspinal muscles. Statically significant post-operative MFI change was only noted in erector spinae muscle at caudal adjacent level and L2-S1 mean global level. COS produces a greater area of decompression on follow up MRI than MIS with no statistical significance on clinical grounds.

Memantine Rescues Neurosyphilis-Related Schizophrenic-like Features and Cognitive Deficit.

OBJECTIVES: Neurosyphilis, an infectious neuroinflammatory disorder, could cause diverse neuropsychiatric symptoms mimicking disorders of schizophrenia and dementia; hence, it is known as the "chameleon of psychiatry." Here, we present a subject with neurosyphilis with schizophrenic features and share the treatment outcome. METHODS: A 42-year-old single man had schizophrenic-like features and cognitive dysfunction for 1 year. Neurosyphilis was confirmed by a cerebral spinal fluid study. The brain image revealed multiple punctuated white matter gliosis in the bilateral frontal lobes and old lacunar infarctions in the bilateral basal hippocampus. The neuropsychiatric functions were declined until adjunctive memantine therapy. RESULTS: With the add-on therapy of memantine 10 mg daily, the psychotic and dementic symptoms markedly improved, and the patient recovered to the premorbid state in the 2-year follow-up course. CONCLUSIONS: Memantine has an adjunctive effect on neurosyphilis-related neuropsychiatric disorder via modulation of the glutamatergic neurotransmission and microglia-induced neuroinflammation.

Characterization of Mechanical Stability and Immunological Compatibility for Functionalized Modification Interfaces.

Surface modification layers are performed on the surfaces of biomaterials and have exhibited promise for decoupling original surface properties from bulk materials and enabling customized and advanced functional properties. The physical stability and the biological compatibility of these modified layers are equally important to ensure minimized delamination, debris, leaching of molecules, and other problems that are related to the failure of the modification layers and thus can provide a long-term success for the uses of these modified layers. A proven surface modification tool of the functionalized poly-para-xylylene (PPX) system was used as an example, and in addition to the demonstration of their chemical conjugation capabilities and the functional properties that have been well-documented, in the present report, we additionally devised the characterization protocols to examine stability properties, including thermostability and adhesive strength, as well as the biocompatibility, including cell viability and the immunological responses, for the modified PPX layers. The results suggested a durable coating stability for PPXs and firmly attached biomolecules under these stability and compatibility tests. The durable and stable modification layers accompanied by the native properties of the PPXs showed high cell viability against fibroblast cells and macrophages (MΦs), and the resulting immunological activities created by the MΦs exhibited excellent compatibility with non-activated immunological responses and no indication of inflammation.

Postural stability and trunk muscle responses to the static and perturbed balance tasks in individuals with and without symptomatic degenerative lumbar disease.

BACKGROUND: Degenerative lumbar diseases (DLDs) are characterized by motor functional deficits and postural instability. In this study, we investigated the differences in the trunk muscle responses to postural control between the presurgical DLD patients and healthy individuals while performing the static and perturbed balance tasks. METHODS: Thirty-five DLD patients (aged 61.1 ±â€¯8.0 years) and thirty-five asymptomatic controls (aged 62.9 ±â€¯3.7 years) participated in this study. All participants stood on a force plate and performed the quiet standing (QS) and in situ weight-lifting (WL) tasks. The participants' performance in the QS task was tested under the eyes-open, eyes-closed, wide-base, and narrow-base conditions. Center of pressure (CoP) movements and electromyography of the erector spinae (ES) were recorded. The Mann-Whitney U test was applied for statistical analysis. RESULTS: The DLD group showed a significantly greater CoP movements and muscle activations during the QS task. Nevertheless, smaller CoP movements were noted during the WL task in the DLD group. Under the eyes-closed and narrow-base conditions, the DLD group showed even higher muscle activations and CoP movements. SIGNIFICANCE: The DLD patients demonstrated a poor postural control ability and tended to rely on the visual feedback and wide-base standing posture. A rigid and restricted posture was also adopted during the perturbed WL task. A high level of ES activation was required to maintain their postural steadiness. This study reveals an aberrant pattern of postural control and trunk muscle activations in symptomatic DLD patients which potentially contributes to the development of beneficial rehabilitation programs.

Role of heel lifting in standing balance recovery: A simulation study.

Although lifting the heels has frequently been observed during balance recovery, the function of this movement has generally been overlooked. The present study aimed to investigate the functional role of heel lifting during regaining balance from a perturbed state. Computer simulation was employed to objectively examine the effect of allowing/constraining heel lifting on balance performance. The human model consisted of 3 rigid body segments connected by frictionless joints. Movements were driven by joint torques depending on current joint angle, angular velocity, and activation level. Starting from forward-inclined and static straight-body postures, the optimization goal was to recover balance effectively (so that ground projection of the mass center returned to the inside of the base of support) and efficiently by adjusting ankle and hip joint activation levels. Allowing/constraining heel lifting resulted in virtually identical movements when balance was mildly perturbed at the smallest lean angle (8°). At larger lean angles (8.5° and 9°), heel lifting assisted balance recovery more evidently with larger joint movements. Partial and altered timings of ankle/hip torque activation due to constraining heel lifting reduced linear and angular momentum generation for avoiding forward falling, and resulted in hindered balancing performance.

Enhanced bone morphogenic property of parylene-C.

The ability to induce osteointegration was introduced to a parylene-C surface via the simple and intuitive process of protein adsorption mediated by hydrophobic interactions. In this way, bone morphogenetic protein (BMP)-2, fibronectin, and platelet-rich plasma (PRP) could be immobilized on parylene-C surfaces. This approach alleviates concerns related to the use of potentially harmful substances in parylene-C modification processes. The adsorbed protein molecules were quantitatively characterized with respect to adsorption efficacy and binding affinity, and the important biological activities of the proteins were also examined using both early and late markers of osteogenetic activity, including alkaline phosphatase expression, calcium mineralization and marker gene expression. Additionally, the adsorbed PRP exhibited potential as a substitute for expensive recombinant growth factors by effectively inducing comparable osteogenetic activity. In addition to the excellent biocompatibility of parylene-C and its ability to coat a wide variety of substrate materials, the modification of parylene-C via protein adsorption provides unlimited possibilities for installing specific biological functions, expanding the potential applications of this material to include various biointerface platforms.

Temperature coefficient of frequency modeling for CMOS-MEMS bulk mode composite resonators.

CMOS-MEMS resonators, which are promising building blocks for achieving monolithic integration of MEMS structure, can be used for timing and filtering applications, and control circuitry. SiO2 has been used to make MEMS resonators with quality factor Q > 10(4), but temperature instability remains a major challenge. In this paper, a design that uses an embedded metal block for temperature compensation is proposed and shows sub-ppm temperature stability (-0.21 ppm/K). A comprehensive analytical model is derived and applied to analyze and optimize the temperature coefficient of frequency (TCF) of the CMOS-MEMS composite material resonator. Comparison with finite element method simulation demonstrates good accuracy. The model can also be applied to predict and analyze the TCF of MEMS resonators with arbitrary mode shape, and its integration with simulation packages enables interactive and efficient design process.

Percutaneous balloon kyphoplasty for the treatment of vertebral compression fractures.

BACKGROUND: Vertebral compression fractures (VCFs) constitute a major health care problem, not only because of their high incidence but also because of their direct and indirect negative impacts on both patients' health-related quality of life and costs to the health care system. Two minimally invasive surgical approaches were developed for the management of symptomatic VCFs: balloon kyphoplasty and vertebroplasty. The purpose of this study was to evaluate the effectiveness and safety of balloon kyphoplasty in the treatment of symptomatic VCFs. METHODS: Between July 2011 and June 2012, one hundred and eighty-seven patients with two hundred and fifty-one vertebras received balloon kyphoplasty in our hospital. There were sixty-five male and one hundred and twenty-two female patients with an average age of 74.5 (range, 61 to 95 years). The pain symptoms and quality of life, were measured before operation and at one day, three months, six months and one year following kyphoplasty. Radiographic data including restoration of kyphotic angle, anterior vertebral height, and any leakage of cement were defined. RESULTS: The mean visual analog pain scale decreased from a preoperative value of 7.7 to 2.2 at one day (p < .05) following operation and the Oswestry Disability Index improved from 56.8 to 18.3 (p < .05). The kyphotic angle improved from a mean of 14.4° before surgery to 6.7° at one day after surgery (p < .05). The mean anterior vertebral height increased significantly from 52% before surgery to 74.5% at one day after surgery (p < .05) and 70.2% at one year follow-up. Minor cement extravasations were observed in twenty-nine out of two hundred and fifty-one procedures, including six leakage via basivertebral vein, three leakage via segmental vein and twenty leakage through a cortical defect. None of the leakages were associated with any clinical consequences. CONCLUSIONS: Balloon kyphoplasty not only rapidly reduced pain and disability but also restored sagittal alignment in our patients at one-year follow-up. The treatment of osteoporotic vertebral compression fractures with balloon kyphoplasty is a safe, effective, and minimally invasive procedure that provides satisfactory clinical results.

Mechanically coupled CMOS-MEMS free-free beam resonator arrays with enhanced power handling capability.

Integrated CMOS-MEMS free-free beam resonator arrays operated in a standard two-port electrical configuration with low motional impedance and high power handling capability, centered at 10.5 MHz, have been demonstrated using the combination of pull-in gap reduction mechanism and mechanically coupled array design. The mechanical links (i.e., coupling elements) using short stubs connect each constituent resonator of an array to its adjacent ones at the high-velocity vibrating locations to accentuate the desired mode and reject all other spurious modes. A single second-mode free-free beam resonator with quality factor Q > 2200 and motional impedance R(m) < 150 kΩ has been used to achieve mechanically coupled resonator arrays in this work. In array design, a 9-resonator array has been experimentally characterized to have performance improvement of approximately 10× on motional impedance and power handling as compared with that of a single resonator. In addition, the two-port electrical configuration is much preferred over a one-port configuration because of its low-feedthrough and high design flexibility for future oscillator and filter implementation.

In vitro activities of daptomycin-, vancomycin-, and teicoplanin-loaded polymethylmethacrylate against methicillin-susceptible, methicillin-resistant, and vancomycin-intermediate strains of Staphylococcus aureus.

The objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated using in vitro broth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against different Staphylococcus aureus strains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment of Staphylococcus aureus infection, teicoplanin was superior in terms of antibacterial effects.

Ischemic orbital compartment syndrome after posterior spinal surgery.

STUDY DESIGN: Case report. OBJECTIVE: To describe a patient with ischemic orbital compartment syndrome after undergoing spinal surgery in a prone position. SUMMARY OF BACKGROUND DATA: Ocular complications after nonocular surgery are devastating. The most common etiology is ischemic optic neuropathy. Orbital compartment syndrome with ischemic change is quite rare and urgent management is necessary. METHODS: Early diagnosis and surgical intervention was performed for ischemic compartment syndrome after posterior spinal surgery was done. RESULTS: Despite immediate management, the patient remained blind and ptotic 3 months after the injury. CONCLUSION: Understanding ocular complications after spinal surgery is vital. Although rare, but the most troublesome complication is ischemic orbital compartment syndrome.