Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients.

PURPOSE: We aimed to identify the differently expressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant systemic therapy with trastuzumab in HER2-positive breast cancer patients. METHODS: This study was retrospectively analyzed from consecutively collected patient data. We recruited 64 women with breast cancer and categorized them into 3 groups: complete response (CR), partial response (PR), and drug resistance (DR). The final number of patients in the study was 20. RNA from 20 core needle biopsy paraffin-embedded tissues and 4 cultured cell lines (SKBR3 and BT474 breast cancer parent cells and cultured resistant cells) was extracted, reverse transcribed, and subjected to GeneChip array analysis. The obtained data were analyzed using Gene Ontology, Kyoto Gene and Genome Encyclopedia, Database for Annotation, Visualization and Integrated Discovery. RESULTS: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines were identified. Among these, 3,224 were upregulated and 3,432 were downregulated. Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment in HER2-type breast cancer, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in the CR group. CONCLUSIONS: This multigene assay-based study provides insights into breast cancer signaling and possible predictions of therapeutic response to targeted therapies such as trastuzumab.

Demyelinating polyneuropathy combined with brachial plexopathy after nivolumab therapy for hodgkin lymphoma: a case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor that targets the programmed cell death-1 protein and is effective in treating advanced cancer. However, it is also associated with various immune-related neurological complications, including myasthenia gravis, Guillain-Barré syndrome, and demyelinating polyneuropathy. These complications can easily mimic other neurological diseases and have greatly varying therapeutic approaches depending on the underlying pathophysiology. CASE PRESENTATION: Here, we report a case of nivolumab-induced demyelinating peripheral polyneuropathy involving the brachial plexus in a patient with Hodgkin lymphoma. Approximately 7 months after nivolumab treatment, the patient experienced muscle weakness with a tightness and tingling sensation in the right forearm. Electrodiagnostic studies showed features of demyelinating peripheral neuropathy with right brachial plexopathy. Magnetic resonance imaging revealed thickening with a diffuse enhancement of both brachial plexuses. The patient was eventually diagnosed with nivolumab-induced demyelinating polyneuropathy involving the brachial plexus. Oral steroid therapy improved motor weakness and sensory abnormalities without aggravation. CONCLUSION: Our study indicates the possibility of nivolumab-induced neuropathies in cases involving muscle weakness with sensory abnormalities of the upper extremity following nivolumab administration in patients with advanced cancer. Comprehensive electrodiagnostic studies and magnetic resonance imaging are helpful in the differential diagnosis of other neurological diseases. Appropriate diagnostic and therapeutic approaches may prevent further neurological deterioration.

A Pneumatically Controlled Prosthetic Socket for Transfemoral Amputees.

Amputees typically experience changes in residual limb volume in their daily lives. It causes an uncomfortable fit of the socket by applying high pressure on the sensitive area of the residual limb or by loosening the socket. In this study, we developed a transfemoral prosthetic socket for above-the-knee amputees that ensures a good socket fit by maintaining uniform and constant contact pressure despite volume changes in the residual limb. The socket has two air bladders in the posterior femoral region, and the pneumatic controller is located on the tibia of the prosthesis. The pneumatic system aims to minimize unstable fitting of the socket and improve walking performance by inflating or deflating the air bladder. The developed socket autonomously maintains the air pressure inside the prosthetic socket at a steady-state error of 3 mmHg or less by adjusting the amount of air in the air bladder via closed-loop control. In the clinical trial, amputee participants walked on flat and inclined surfaces. The displacement between the residual limb and socket during the gait cycle was reduced by up to 33.4% after air injection into the socket. The inflatable bladder increased the knee flexion angle on the affected side, resulting in increased stride length and gait velocity. The pneumatic socket provides a stable and comfortable walking experience not only when walking on flat ground but also on slopes.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular (LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

Novel Animal Model of Spontaneous Cerebral Petechial Hemorrhage Using Focused Ultrasound in Rats.

Background and Objectives: Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood-brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. Materials and Methods: Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). Results: This method increases the permeability of the blood-brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. Conclusions: We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages.

Elevated TRPV4 Levels Contribute to Endothelial Damage and Scarring in Experimental Spinal Cord Injury.

Currently, the role of transient receptor potential vanilloid type 4 (TRPV4), a nonselective cation channel in the pathology of spinal cord injury (SCI), is not recognized. Herein, we report the expression and contribution of TRPV4 in the pathology of scarring and endothelial and secondary damage after SCI. TRPV4 expression increased during the inflammatory phase in female rats after SCI and was expressed primarily by cells at endothelial-microglial junctions. Two-photon microscopy of intracellular-free Ca2+ levels revealed a biphasic increase at similar time points after SCI. Expression of TRPV4 at the injury epicenter, but not intracellular-free Ca2+, progressively increases with the severity of the injury. Activation of TRPV4 with specific agonist altered the organization of endothelial cells, affected tight junctions in the hCMEC/D3 BBB cell line in vitro, and increases the scarring in rat spinal cord as well as induced endothelial damage. By contrast, suppression of TRPV4 with a specific antagonist or in female Trpv4 KO mouse attenuated inflammatory cytokines and chemokines, prevented the degradation of tight junction proteins, and preserve blood-spinal cord barrier integrity, thereby attenuate the scarring after SCI. Likewise, secondary damage was reduced, and behavioral outcomes were improved in Trpv4 KO mice after SCI. These results suggest that increased TRPV4 expression disrupts endothelial cell organization during the early inflammatory phase of SCI, resulting in tissue damage, vascular destabilization, blood-spinal cord barrier breakdown, and scarring. Thus, TRPV4 inhibition/knockdown represents a promising therapeutic strategy to stabilize/protect endothelial cells, attenuate nociception and secondary damage, and reduce scarring after SCI.SIGNIFICANCE STATEMENT TRPV4, a calcium-permeable nonselective cation channel, is widely expressed in both excitable and nonexcitable cells. Spinal cord injury (SCI) majorly caused by trauma/accidents is associated with changes in osmolarity, mechanical injury, and shear stress. After SCI, TRPV4 was increased and were found to be linked with the severity of injury at the epicenter at the time points that were reported to be critical for repair/treatment. Activation of TRPV4 was damaging to endothelial cells that form the blood-spinal cord barrier and thus contributes to scarring (glial and fibrotic). Importantly, inhibition/knockdown of TRPV4 prevented these effects. Thus, the manipulation of TRPV4 signaling might lead to new therapeutic strategies or combinatorial therapies to protect endothelial cells and enhance repair after SCI.

Genetic Therapy for Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.

The inhibitory effect of curcumin via fascin suppression through JAK/STAT3 pathway on metastasis and recurrence of ovary cancer cells.

BACKGROUND: Fascin is an actin-binding protein and highly expressed in ovarian cancer cells. It is associated with metastasis of cancer and may be a useful prognostic factor. Anticancer activity of curcumin is related to its effect on several signaling mechanisms. Although there have been many reports regarding the anticancer properties of curcumin, its inhibitory effects on migration and invasion of ovarian cancer cells, particularly in the context of fascin expression, have not been reported. The purpose of this study was to investigate the effect of curcumin on fascin expression in ovarian cancer cells and to propose a possible mechanism for the anticancer activity of curcumin through reduced fascin expression. METHODS: SKOV3, human epithelial ovary cancer cell line, was cultured with curcumin at various dose and duration. The fascin was quantified using cell viability test and Western blot. To determine the effect of curcumin on the upstream pathway of fascin expression, the signal transducer and activator of transcription 3 (STAT3) was analyzed by sandwich-ELISA. Attachment assay, migration assay and invasion assay were analyzed to approve the change of cellular invasiveness of ovary cancer after curcumin. To determine the morphological changes of ovarian cancer cells by curcumin, immunofluorescence was performed. RESULTS: MTS assays showed that cell viability was different at various concentration of curcumin, and as concentration increased, cell viability tended to decrease. Curcumin appears to suppress fascin expression, even with a minimal concentration and short exposure time. Also, curcumin may suppress fascin expression in ovarian cancer cells through STAT3 downregulation. The attachment assay, migration assay and invasion assay of the ovarian cancer cells exhibited a statistically significant decrease. Immunofluorescence revealed a change of cell shape from a typical form of uninfluenced cells to a more polygonal appearance, with a significant reduction in filopodia formation. CONCLUSIONS: Curcumin reduces fascin expression through JAK/STAT3 pathway inhibition, which interferes with the cellular interactions essential for the metastasis and recurrence of ovarian cancer cells. Higher curcumin concentrations and longer exposure times concomitantly decreased fascin expression.

The Role of Epigenomics in Osteoporosis and Osteoporotic Vertebral Fracture.

Osteoporosis is a complex multifactorial condition of the musculoskeletal system. Osteoporosis and osteoporotic vertebral fracture (OVF) are associated with high medical costs and can lead to poor quality of life. Genetic factors are important in determining bone mass and structure, as well as any predisposition for bone degradation and OVF. However, genetic factors are not enough to explain osteoporosis development and OVF occurrence. Epigenetics describes a mechanism for controlling gene expression and cellular processes without altering DNA sequences. The main mechanisms in epigenetics are DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). Recently, alterations in epigenetic mechanisms and their activity have been associated with osteoporosis and OVF. Here, we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling. A progressive understanding of normal bone metabolism and the role of epigenetic mechanisms in multifactorial osteopathy can help us better understand the etiology of the disease and convert this information into clinical practice. A deep understanding of these mechanisms will help in properly coordinating future individual treatments of osteoporosis and OVF.

Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis.

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.

An Injectable Hyaluronan-Methylcellulose (HAMC) Hydrogel Combined with Wharton's Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair.

Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan-methylcellulose (HAMC) hydrogels loaded with Wharton's Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 104 cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration.

4-O-methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK-mediated cardiac lipid metabolism improvement.

Diabetic cardiomyopathy (DCM) is characterized by increased left ventricular mass and wall thickness, decreased systolic function, reduced ejection fraction (EF) and ultimately heart failure. The 4-O-methylhonokiol (MH) has been isolated mainly from the bark of the root and stem of Magnolia species. In this study, we aimed to elucidate whether MH can effectively prevent DCM in type 2 diabetic (T2D) mice and, if so, whether the protective response of MH is associated with its activation of AMPK-mediated inhibition of lipid accumulation and inflammation. A total number of 40 mice were divided into four groups: Ctrl, Ctrl + MH, T2D, T2D + MH. Five mice from each group were sacrificed after 3-month MH treatment. The remaining animals in each group were kept for additional 3 months without further MH treatment. In T2D mice, the typical DCM symptoms were induced as expected, reflected by decreased ejection fraction and lipotoxic effects inducing lipid accumulation, oxidative stress, inflammatory reactions, and final fibrosis. However, these typical DCM changes were significantly prevented by the MH treatment immediately or 3 months after the 3-month MH treatment, suggesting MH-induced cardiac protection from T2D had a memory effect. Mechanistically, MH cardiac protection from DCM may be associated with its lipid metabolism improvement by the activation of AMPK/CPT1-mediated fatty acid oxidation. In addition, the MH treatment of DCM mice significantly improved their insulin resistance levels by activation of GSK-3ß. These results indicate that the treatment of T2D with MH effectively prevents DCM probably via AMPK-dependent improvement of the lipid metabolism.

4-O-methylhonokiol ameliorates type 2 diabetes-induced nephropathy in mice likely by activation of AMPK-mediated fatty acid oxidation and Nrf2-mediated anti-oxidative stress.

Diabetic nephropathy (DN) is one of the most serious long-term complications of type 2 diabetes (T2D). 4-O-methylhonokiol (MH) is one of the biologically active ingredients extracted from the Magnolia stem bark. In this study, we aim to elucidate whether treatment with MH can ameliorate or slow-down progression of DN in a T2D murine model and, if so, whether the protective response of MH correlates with AMPK-associated anti-oxidant and anti-inflammatory effects. To induce T2D, mice were fed normal diet (ND) or high fat diet (HFD) for 3 months to induce insulin resistance, followed by an intraperitoneal injection of STZ to induce hyperglycemia. Both T2D and control mice received gavage containing vehicle or MH once diabetes onset for 3 months. Once completing 3-month MH treatment, five mice from each group were sacrificed as 3 month time-point. The rest mice in each group were sacrificed 3 months later as 6 month time-point. In T2D mice, the typical DN symptoms were induced as expected, reflected by increased proteinuria, renal lipid accumulation and lipotoxic effects inducing oxidative stress, and inflammatory reactions, and final fibrosis. However, these typical DN changes were significantly prevented by MH treatment for 3 months and even at 3 months post-MH withdrawal. Mechanistically, MH renal-protection from DN may be related to lipid metabolic improvement and oxidative stress attenuation along with increases in AMPK/PGC-1α/CPT1B-mediated fatty acid oxidation and Nrf2/SOD2-mediated anti-oxidative stress. Results showed the preventive effect of MH on the renal oxidative stress and inflammation in DN.

New Observation Structural Change from O3 to P2 Type by Changing Sodium Contents for Na-Ion Batteries.

Stable Na+-ion-storage cathodes with adequate reversible capacities are increasingly needed for the application of Na-ion batteries in large-scale, low-cost electric storage systems. Ion-storage oxides have been classified into P2- and O3-type phases based on their sodium content. There have been few studies on the structural stability and electrochemical properties of such oxides. Here, we report the synthesis of a sodium-ion battery (SIB) cathode material Nax[Ni0.8Co0.1Mn0.1]O2 (x = 0.67, 1) using a hydroxide co-precipitation method. The effects of different sodium contents on the structural and electrochemical properties of this cathode material were studied. The results indicated better electrochemical performance of the P2-type materials compared to the O3-type in terms of high discharge capacity and good cycling performance. The P2-Na0.67[Ni0.8Co0.1Mn0.1]O2 cathode exhibited a good charge storage capacity of 108.74 mAhg-1, with a capacity retention of over 67% after 50 voltage cycles (between 2.0 and 4.5 V) at 0.1 C. The developed material may potentially be used as a cathode in sodium-ion batteries.

A Highly Efficient Absorbent for Various Organic Solvents Using Hydrophobic Graphene-Sponge Composite.

We propose a hydrophobic graphene-sponge composite produced by embedding graphene flakes within polyurethane sponge as a selective absorbent for hydrophobic liquids from a contaminated water mixture. The self-aggregation nature of graphene flakes effectively allows higher graphene content to be added inside the polyurethane sponge with repeated dip-coating. High hydrophobicity due to the intrinsic nature graphene surface allows the selective absorption of liquid contaminants from a water mixture. Given the porous structure of the composite, absorption capability of 134-233 times its own weight towards various hydrophobic liquids is possible.

Myelopathy associated with instability consequent to resection of ossification of anterior longitudinal ligament in DISH.

PURPOSE: The presence of prominent OALL (ossification of anterior longitudinal ligament) in the anterior cervical spine has been implicated as a cause of dysphagia. Surgical resection of the OALL is considered effective for the management of diffuse idiopathic skeletal hyperostosis (DISH)-related dysphagia. Although many reports have been published on DISH-related dysphagia, no cases of postoperative cervical instability have been reported thus far. We present a case in which the patient developed myelopathy associated with instability consequent to resection of OALL in DISH. METHODS: A 62-year-old man presented with progressive dysphagia that persisted for a year. The patient's symptoms were successfully resolved by resection of OALL. Five years after the surgery, the dysphagia resurfaced and was found to be caused by the regrowth of the OALL. A repeat surgery was performed, and the dysphagia disappeared. Eleven months after the second surgery, he visited the hospital with progressive quadriparesis and pain in the cervical region. RESULTS: Nine-month follow-up radiologic study revealed cervical instability at the level of C5-6 resulting in myelopathy. The patient underwent decompressive laminectomy and posterior fusion surgery. CONCLUSION: Surgical resection of DISH-related dysphagia typically yields excellent outcomes, but our experience in this case highlights the possibility of OALL regrowth and subsequent cervical instability after resection of OALL.

Recurrent esophageal perforation after anterior cervical spine surgery: case report.

PURPOSE: Delayed esophageal perforation after anterior cervical discectomy and fusion (ACDF) is an extremely rare cause of infection such as spondylodiscitis. We present a rare case in which a patient had two delayed esophageal perforations occurring 20 and 25 years after ACDF. By sharing our experience of this rare case, we hope to provide new information related to delayed esophageal perforation. METHODS: We present the case of a 72-year-old patient who underwent ACDF due to cervical spondylosis 25 years ago. Delayed esophageal perforation occurred 20 years postoperatively and healed spontaneously with conservative treatment. RESULTS: Five years later, a second esophageal perforation occurred, which required surgical intervention and involved recurrent infection. CONCLUSIONS: We suggest that it is important to consider follow-up in patients with spontaneously healed esophageal perforations. Furthermore, any patient with symptoms subsequent to a spontaneously healed esophageal perforation, even after an interval of several years, should receive a thorough evaluation for possible recurrent esophageal perforation.

Changes in cervical motion after cervical spinal motion preservation surgery.

BACKGROUND: For patients with single-level cervical radiculopathy, various types of motion preservation surgeries, such as total disc replacement (TDR), posterior cervical foraminotomy (PCF) and posterior percutaneous endoscopic foraminotomy and discectomy (PECF), are available. In addition to motion preservation, the quality of motion is an important issue. The aim of the present study was to evaluate the influence of these surgeries on cervical motion by comparing the instantaneous axis of rotation (IAR) among PECF, TDR and PCF at the index and superior/inferior adjacent segments. METHODS: A retrospective review was performed of patients who underwent index surgery at C5-6 for cervical single-level foraminal disc herniation or foraminal stenosis. Patients with minimal degeneration at the index and other cervical spinal levels and flexion/extension cervical lateral radiographs both preoperatively and 6 months postoperatively were included (PECF, 11 patients; TDR, 11 patients; PCF, 12 patients). The IARs were calculated at the index segment and segments above and below the index segment from the flexion and extension cervical lateral radiographs, which were obtained preoperatively and 6 months postoperatively. A standardized cervical normogram was referenced to qualify shifts in the IAR. RESULTS: Postoperatively, neck pain was significantly decreased, with no difference among the surgical methods. The IARs were not significantly changed after the PECF. Although significant inferior shift occurred at C6-7 after TDR (p = 0.02), the shift occurred within the normal range in the cervical normogram. However, significant inferior shifts in the IARs occurred after PCF at C5-6 (p = 0.02) and C6-7 (p = 0.02), and the IARs moved out of the normal range. CONCLUSIONS: The IARs were significantly changed after PCF at either the index segment or the adjacent segment below. The shifts in IAR at the index and adjacent segments were not significant after PECF and TDR. The sample size was too small to allow definitive conclusions, but the present study showed that PECF may be another alternative to motion preservation surgeries.

Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts.

Hematopoietic stem/progenitor cell (HSPC) mobilization is an essential homeostatic process regulated by the interaction of cellular and molecular components in bone marrow niches. It has been shown by others that neurotransmitters released from the sympathetic nervous system regulate HSPC egress from bone marrow to peripheral blood. In this study, we investigate the functional role of neuropeptide Y (NPY) on this process. NPY deficient mice had significantly impaired HSPC mobilization due to increased expression of HSPC maintenance factors by reduction of matrix metalloproteinase-9 (MMP-9) activity in bone marrow. Pharmacological or endogenous elevation of NPY led to decrease of HSPC maintenance factors expression by activating MMP-9 in osteoblasts, resulting in HSPC mobilization. Mice in which the Y1 receptor was deleted in osteoblasts did not exhibit HSPC mobilization by NPY. Furthermore, NPY treatment in ovariectomized mice caused reduction of bone loss due to HSPC mobilization. These results suggest a new role of NPY on HSPC mobilization, as well as the potential therapeutic application of this neuropeptide for stem cell-based therapy. Stem Cells 2016;34:2145-2156.

Long-term recurrence rates after the removal of spinal meningiomas in relation to Simpson grades.

PURPOSE: Simpson grade II removal (coagulation of the dural attachment after gross total removal) of spinal meningioma is considered an acceptable alternative, but increased recurrence after more than 10 years has been reported. More attention must be paid to the long-term surgical outcomes after Simpson grade II removal. METHODS: A retrospective review was performed for 20 patients (M:F = 5:15; age, 59 ± 9 years) with Simpson grade II removal (mean follow-up period, 12.9 years; range 10.0-17.5). Magnetic resonance (MR) imaging was conducted in 17 patients at 88 ± 52 months (range 12-157). During the same period, Simpson grade I removal (removal of the dural origin) was performed in 21 patients (follow-up, 89 ± 87 months; range 9-316). Radiological recurrence was defined as a visible tumor on a follow-up MR image, and clinical tumor recurrence was defined as the recurrence of symptoms. RESULTS: At the final follow-up, neurological symptoms had improved in 16/20 patients and remained stable in 4/20. A recurrent tumor was detected in one patient due to increased back pain at 92 months postoperative, but the symptom was stable without surgery until the last follow-up (124 months). The radiological and clinical recurrence-free survival periods were 150 ± 7 months (95 % CI 136-163) and 204 ± 6 months (95 % CI 193-215), respectively. There was no recurrence after Simpson grade I removal, whereas neurological deterioration occurred in two patients after surgery. CONCLUSIONS: Simpson grade II removal may be an alternative option if the risk of complications with Simpson grade I removal is expected to be high.