Biodegradable microneedle acupuncture has equivalent efficacy to traditional intradermal acupuncture for dry eye disease: A pilot single-blinded, randomized controlled trial.

BACKGROUND: Dry eye disease (DED) is a common ocular disorder in which the tear film cannot maintain homeostasis. Acupuncture has been used to treat DED in Korean medicine. Particularly, intradermal acupuncture (IDA) is less painful and enables free movement after treatment. However, it can also provoke allergic reactions to metal. To overcome this, biodegradable microneedle acupuncture (BMA) has been developed. This study compared BMA with traditional IDA in terms of efficacy and safety in patients with DED. METHODS: This study was designed as an investigator-initiated, assessor-blinded, single-center, parallel randomized controlled trial. Thirty patients with DED were enrolled and randomized to one of the treatments. One group was treated with BMA on the acupoints, including bilateral BL2, GB14, TE23, EX-HN5, and ST1. The other group was treated with traditional IDA at the same acupoints. Treatments were conducted 3 times a week for 4 weeks. The major endpoint was ocular surface disease index (OSDI). The minor endpoints were subjective symptoms visual analog scale (VAS), quality of life (QoL), and tear production measured by the Schirmer I test. RESULTS: All enrolled participants successfully completed the trial, and all of their data was analyzed. Both treatments remarkably improved the OSDI score, VAS score, QoL score, and tear secretion after 4 weeks (P < .05). Except for tear production in the left eye (P < .05), there were no statistical differences between the 2 treatments on the final visit (P > .05). No adverse events were observed. CONCLUSION: BMA and IDA had the same therapeutic effect for improving DED and both were safe. BMA can be used in patients with DED as an alternative to traditional IDA.

Safety and efficacy of combined acupuncture (body and intradermal acupuncture) for dry eye disease: study protocol for a pilot, single-centre, assessor-blinded, randomised, artificial tear drop-controlled trial at Naju Dongshin University Korean Medicine Hospital.

INTRODUCTION: The prevalence of dry eye disease (DED) has been consistently increasing yearly. However, the radical therapy has not yet been established. This study is to confirm the superiority of acupuncture over artificial tear drops (ATDs) in patients with DED. METHODS AND ANALYSIS: This study is a single-centre, investigator-initiated, assessor-blinded, parallel randomised controlled trial. 30 participants will be enrolled. Over a period of 4 weeks, the experimental group would receive two kinds of acupuncture three times a week. First, body acupuncture would be performed on bilateral BL2, GB14, TE23, EX-HN5 and ST1 for 15 min. Thereafter, intradermal acupuncture would be performed on the same acupoints for 4 hours. On the other hand, the control group would apply the provided ATD at least four times a day. As a rescue medication for severe DED symptoms, both groups can additionally apply ATD. The frequency of ATD use would be recorded during the trial. The primary outcomes are the Ocular Surface Disease Index and tear film break-up time. The secondary outcomes are subjective symptom Visual Analogue Scale, quality of life, Schirmer I test, tear lactoferrin level, treatment satisfaction and safety. The outcomes would be mostly assessed at visits 1, 13 and 14. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of Naju Dongshin University Korean Medicine Hospital (Approval No. NJ-IRB-23-5). The obtained results will be disseminated through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: KCT0008563.

Detecting causal relationship of non-floodplain wetland hydrologic connectivity using convergent cross mapping.

The hydrologic connectivity of non-floodplain wetlands (NFWs) with downstream water (DW) has gained increased importance, but connectivity via groundwater (GW) is largely unknown owing to the high complexity of hydrological processes and climatic seasonality. In this study, a causal inference method, convergent cross mapping (CCM), was applied to detect the hydrologic causality between upland NFW and DW through GW. CCM is a nonlinear inference method for detecting causal relationships among environmental variables with weak or moderate coupling in nonlinear dynamical systems. We assumed that causation would exist when the following conditions were observed: (1) the presence of two direct causal (NFW → GW and GW → DW) and one indirect causal (NFW → DW) relationship; (2) a nonexistent opposite causal relationship (DW → NFW); (3) the two direct causations with shorter lag times relative to indirect causation; and (4) similar patterns not observed with pseudo DW. The water levels monitored by a well and piezometer represented NFW and GW measurements, respectively, and the DW was indicated by the baseflow at the outlet of the drainage area, including NFW. To elucidate causality, the DW taken at the adjacent drainage area with similar climatic seasonality was also tested as pseudo DW. The CCM results showed that the water flow from NFW to GW and then DW was only present, and any opposite flows did not exist. In addition, direct causations had shorter lag time than indirect causation, and 3-day lag time was shown between NFW and DW. Interestingly, the results with pseudo DW did not show any lagged interactions, indicating non-causation. These results provide the signals for the hydrologic connectivity of NFW and DW with GW. Therefore, this study would support the importance of NFW protection and management.

A comparative study on a biodegradable hyaluronic acid microneedle patch with a needleless patch for dry skin in atopic dermatitis: a single-blinded, split-body, randomized controlled trial.

To overcome interruption of skin barrier in transdermal drug delivery, the microneedle (MN) patch penetrates the barrier by punching with its MNs. Setting a needleless patch (NL patch) as the control intervention, this study assessed the efficacy of a biodegradable hyaluronic acid MN patch (BHMN patch) for atopic dermatitis (AD) patients with dry skin. Similar two AD lesions were selected from the extremities of a participant. For one lesion, a BHMN patch was attached for 6-8 h on where an aroma cream was applied (BHMN patch group). Simultaneously, an NL patch was attached on the other lesion as in the BHMN patch group (NL patch group). For 2 weeks, the interventions were conducted 3 times a week. The local scoring AD (L-SCORAD) index, the visual analog scale for pruritus and skin dryness, skin hydration, the transepidermal water loss (TEWL), and safety were assessed. Fifteen participants finished this trial with no dropouts. Both groups improved the L-SCORAD index after 2 weeks (p < 0.05), but the score of the BHMN patch group decreased more than that of the NL patch group (p < 0.05). The other outcomes, except for the TEWL, also showed statistical significance in intragroup comparisons. Nevertheless, none of the other outcomes showed statistical significance in intergroup comparisons. The TEWL showed no statistical significance even in intragroup comparison. Recoverable minor adverse events were reported in three cases. Considering the result of L-SCORAD index, the BHMN patch may be effective for ameliorating AD. However, a large-scale confirmatory trial is necessary to reassess other outcomes.Trial Registration: This study was registered with the Clinical Research Information Service, Republic of Korea (Submitted date: 04/01/2022, Registered date: 23/02/2022, The first participant enrollment: 01/12/2021, Registration No. KCT0007037).

A comparative investigator-initiated pilot study on the efficacy and safety of biodegradable microneedle acupuncture and conventional intradermal acupuncture for dry eye patient: A superiority, assessor-blinded, randomized controlled trial.

BACKGROUND: The prevalence of dry eye, which is a common lacrimal disease, is steadily increasing in modern society. However, fundamental treatment for it has not yet been established. This study aims to assess the efficacy and safety of a novel medical device, the biodegradable microneedle acupuncture (BMA), using a traditional intradermal acupuncture needle as the control acupuncture for dry eye. METHOD: This study will be an investigator-initiated, assessor-blinded, comparative, superiority pilot randomized controlled trial. A total of 30 patients with dry eye will be randomly assigned to the experimental or the control group in equal proportion. For the experimental group, the BMA will be applied to both sides of 5 acupoints including BL2, GB14, TE23, EX-HN5, and ST1. For the control group, conventional intradermal acupuncture will be applied to the same acupoints. The needles will be attached for 4 hours. Over 4 weeks, both the interventions will be performed 12 times in total. The primary outcome would be the ocular surface disease index. The secondary outcomes would be the visual analog scale for subjective symptoms, quality of life, Schirmer I test, and general assessment. DISCUSSION: The findings of this study on the efficacy and safety of the BMA would be helpful for patients with dry eye in clinical practice. Further, these results would provide for the foundation of a large-scale BMA study.

Highly Efficient and Flexible Photosensors with GaN Nanowires Horizontally Embedded in a Graphene Sandwich Channel.

In this study, we report highly efficient and flexible photosensors with GaN nanowires (NWs) horizontally embedded in a graphene sandwich structure fabricated on polyethylene terephthalate. GaN NWs and the graphene sandwich structure are used as light-absorbing media and the channel for carrier movement, respectively. To form uniform high-quality crystalline GaN NWs on Si(111) substrates, the initial nucleation behavior of the NWs was manipulated by applying the new growth technique of Ga predeposition. High-resolution transmission electron microscopic images obtained along the vertical direction of GaN NWs showed that stacking faults, typically observed in Si-based (In,Ga)As NWs, were rare. Consequently, narrow and strong optical emission was observed from the GaN NWs at wavelengths of 365.12 nm at 300 K. The photocurrent and photoresponsivity of the flexible photosensor with 802 nm long GaN NWs horizontally embedded in the graphene sandwich channel were measured as 9.17 mA and 91.70 A/W, respectively, at the light intensity of 100 mW/cm2, which are much higher than those previously reported. The high optical-to-electrical conversion characteristics of our flexible photosensors are attributed to the increase in the effective interface between the light-absorbing media and the carrier channel by the horizontal distribution of the GaN NWs within the graphene sandwich structure. After 200 cyclic-bending test of the GaN NW photosensor at the strain of 3%, the photoresponsivity under strain was measured as 89.04 A/W at 100 mW/cm2, corresponding to 97.1% of the photoresponsivity obtained before bending. The photosensor proposed in this study is relatively simple in device design and fabrication, and it requires no sophisticated nanostructural design to minimize the resistance to metal contacts.

Quercetin and fisetin enhanced the small intestine cellular uptake and plasma levels of epi-catechins in in vitro and in vivo models.

Quercetin and fisetin, known as catechol-containing flavonoids, could positively affect the absorption of catechins due to their strong affinity for catechol-O-methyl transferase (COMT), which can methylate and cause the excretion of catechins. The current study examined the effect of quercetin and fisetin on the absorption of epi-catechins (ECs) by using a Caco-2 cell line and an in vivo model. The intestinal transport of total catechins by Caco-2 cells was enhanced from 1.3- to 1.6-fold and 1.4- to 1.7-fold by adding quercetin and fisetin, respectively, compared to the control. It was even higher in the treatment with a mixture of quercetin and fisetin. While EC had the highest value of intestinal transport (169% of the control) in 10% quercetin treatment, EGC (235%), EGCG (244%), and ECG (242%) were significantly transported in the treatment with a 5% mixture of quercetin and fisetin (p < 0.05). In an in vivo pharmacokinetic study, the values of the area under the plasma concentration-time curve (AUC, ng h mL-1) were also higher in rats orally administered EGCG with 10% quercetin (365.5 ± 25.5) or 10% fisetin (825.3 ± 46.7) than in those administered EGCG only (111.3 ± 13.1). Methylated quercetin and methylated fisetin were determined to be m/z 317.24 and m/z 301.25 [M + H]+ with their own product ions, respectively. The results indicate that quercetin or fisetin is superior to ECs for methylation by COMT.

Lack of Cell Proliferative and Tumorigenic Effects of 4-Hydroxyestradiol in the Anterior Pituitary of Rats: Role of Ultrarapid O-Methylation Catalyzed by Pituitary Membrane-Bound Catechol-O-Methyltransferase.

In animal models, estrogens are complete carcinogens in certain target sites. 4-Hydroxyestradiol (4-OH-E2), an endogenous metabolite of 17ß-estradiol (E2), is known to have prominent estrogenic activity plus potential genotoxicity and mutagenicity. We report here our finding that 4-OH-E2 does not induce pituitary tumors in ACI female rats, whereas E2 produces 100% pituitary tumor incidence. To probe the mechanism, we conducted a short-term animal experiment to compare the proliferative effect of 4-OH-E2 in several organs. We found that, whereas 4-OH-E2 had little ability to stimulate pituitary cell proliferation in ovariectomized female rats, it strongly stimulates cell proliferation in certain brain regions of these animals. Further, when we used in vitro cultured rat pituitary tumor cells as models, we found that 4-OH-E2 has similar efficacy as E2 in stimulating cell proliferation, but its potency is approximately 3 orders of magnitude lower than that of E2. Moreover, we found that the pituitary tumor cells have the ability to selectively metabolize 4-OH-E2 (but not E2) with ultrahigh efficiency. Additional analysis revealed that the rat pituitary expresses a membrane-bound catechol-O-methyltransferase that has an ultralow Km value (in nM range) for catechol estrogens. On the basis of these observations, it is concluded that rapid metabolic disposition of 4-OH-E2 through enzymatic O-methylation in rat anterior pituitary cells largely contributes to its apparent lack of cell proliferative and tumorigenic effects in this target site.

Determination of S-methyl-L-methionine (SMM) from Brassicaceae Family Vegetables and Characterization of the Intestinal Transport of SMM by Caco-2 Cells.

The objectives of the current study were to determine S-methyl-L-methionine (SMM) from various Brassicaceae family vegetables by using validated analytical method and to characterize the intestinal transport mechanism of SMM by the Caco-2 cells. The SMM is well known to provide therapeutic activity in peptic ulcers. The amount of SMM from various Brassicaceae family vegetables ranged from 89.08 ± 1.68 µg/g to 535.98 ± 4.85 µg/g of dry weight by using validated ultra-performance liquid chromatography-electrospray ionization-mass spectrometry method. For elucidating intestinal transport mechanism, the cells were incubated with or without transport inhibitors, energy source, or a metabolic inhibitor. Phloridzin and verapamil as inhibitors of sodium glucose transport protein (SGLT1) and P-glycoprotein, respectively, were not responsible for cellular uptake of SMM. Glucose and sodium azide were not affected by the cellular accumulation of SMM. The efflux ratio of SMM was 0.26, implying that it is not effluxed through Caco-2 cells. The apparent coefficient permeability (Papp ) of SMM was 4.69 × 10-5 cm/s, indicating that it will show good oral absorption in in vivo.

Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors in microglia.

Selective elimination of synaptic connections is a common phenomenon which occurs during both developmental and pathological conditions. Glial cells have a central role in the pruning of synapses by specifically engulfing the degenerating neurites of inappropriate connections, but its regulatory mechanisms have been largely unknown. To identify mediators of this process, we established an in vitro cell culture assay for the synapse elimination. Neuronal differentiation and synapse formation of PC12 cells were induced by culturing the cells with nerve growth factor (NGF) in a serum-free medium. To trigger synapse elimination, the NGF-containing medium was replaced with DMEM containing 10% FBS, and the neurites of PC12 cells degenerated within two days. Co-culturing with MG6 cells, a mouse microglial cell line, accelerated the removal of degenerating neurites of PC12 cells by phagocytosis. When MG6 cells were pre-incubated with exosomes secreted from the differentiated PC12 cells after depolarization, the removal was further accelerated by increasing the expression levels of complement component 3 in the MG6 cells. These results define a role for exosomes as a regulator of synapse elimination and clarify a novel mechanism whereby active synapses promote the pruning of inactive ones by stimulating microglial phagocytosis with exosomes.

Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast.

In eukaryotes, the replication of chromosome DNA is coordinated by a replication timing program that temporally regulates the firing of individual replication origins. However, the molecular mechanism underlying the program remains elusive. Here, we report that the telomere-binding protein Taz1 plays a crucial role in the control of replication timing in fission yeast. A DNA element located proximal to a late origin in the chromosome arm represses initiation from the origin in early S phase. Systematic deletion and substitution experiments demonstrated that two tandem telomeric repeats are essential for this repression. The telomeric repeats recruit Taz1, a counterpart of human TRF1 and TRF2, to the locus. Genome-wide analysis revealed that Taz1 regulates about half of chromosomal late origins, including those in subtelomeres. The Taz1-mediated mechanism prevents Dbf4-dependent kinase (DDK)-dependent Sld3 loading onto the origins. Our results demonstrate that the replication timing program in fission yeast uses the internal telomeric repeats and binding of Taz1.

Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death.

Efficacy of multilevel anterior cervical discectomy and fusion versus corpectomy and fusion for multilevel cervical spondylotic myelopathy: a minimum 5-year follow-up study.

PURPOSE: We evaluated radiologic and clinical outcomes to compare the efficacy of anterior cervical discectomy and fusion (ACDF) and anterior corpectomy and fusion (ACCF) for multilevel cervical spondylotic myelopathy (CSM). METHODS: A total of 40 patients who underwent ACDF or ACCF for multilevel CSM were divided into two groups. Group A (n = 25) underwent ACDF and group B (n = 15) ACCF. Clinical outcomes (JOA and VAS scores), perioperative parameters (length of hospital stay, blood loss, operation time), radiological parameters (fusion rate, segmental height, cervical lordosis), and complications were compared. RESULTS: Both group A and group B demonstrated significant increases in JOA scores and significant decreases in VAS. Patients who underwent ACDF experienced significantly shorter hospital stays (p = 0.031), less blood loss (p = 0.001), and shorter operation times (p = 0.024). Both groups showed significant increases in postoperative cervical lordosis and achieved satisfactory fusion rates (88.0 and 93.3%, respectively). There were no significant differences in the incidence of complications among the groups. CONCLUSIONS: Both ACDF and ACCF provide satisfactory clinical outcomes and fusion rates for multilevel CSM. However, multilevel ACDF is associated with better radiologic parameters, shorter hospital stays, less blood loss, and shorter operative times.

Regulation of connexin 36 expression during development.

In the mammalian CNS, the expression of neuronal gap junction protein, connexin 36 (Cx36), increases during the first 2 weeks of postnatal development and then decreases during the following 2 weeks. Recently we showed that the developmental increase in Cx36 expression is augmented by chronic (2 weeks) activation of group II metabotropic glutamate receptors (mGluR), prevented by chronic receptor inactivation, and the receptor-dependent increase in Cx36 expression is regulated via transcriptional control of the Cx36 gene activity. We demonstrate here that acute (60 min) activation of group II mGluRs in developing cortical neuronal cultures causes transient increase in Cx36 protein expression with decrease during the following 24h. However, there is no change in Cx36 mRNA expression. In addition, the data indicate that transient increase in Cx36 expression is due to new protein synthesis. The results suggest that, during development, acute activation of group II mGluRs causes up-regulation of Cx36 via post-transcriptional mechanisms. However, if the receptor activation is sustained, transcriptional activation of the Cx36 gene occurs.

Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury.

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI), and epilepsy. The coupling of neurons by gap junctions (electrical synapses) increases during neuronal injury. We report here that the ischemic increase in neuronal gap junction coupling is regulated by glutamate via group II metabotropic glutamate receptors (mGluRs). Specifically, using electrotonic coupling, Western blots, and siRNA in the mouse somatosensory cortex in vivo and in vitro, we demonstrate that activation of group II mGluRs increases background levels of neuronal gap junction coupling and expression of connexin 36 (Cx36) (neuronal gap junction protein), and inactivation of group II mGluRs prevents the ischemia-mediated increases in the coupling and Cx36 expression. We also show that the regulation is via cAMP/PKA (cAMP-dependent protein kinase)-dependent signaling and posttranscriptional control of Cx36 expression and that other glutamate receptors are not involved in these regulatory mechanisms. Furthermore, using the analysis of neuronal death, we show that inactivation of group II mGluRs or genetic elimination of Cx36 both dramatically reduce ischemia-mediated neuronal death in vitro and in vivo. Similar results are obtained using in vitro models of TBI and epilepsy. Our results indicate that neuronal gap junction coupling is a critical component of glutamate-dependent neuronal death. They also suggest that causal link among group II mGluR function, neuronal gap junction coupling, and neuronal death has a universal character and operates in different types of neuronal injuries.

Radiological changes in anterior cervical discectomy and fusion with cage and plate construct: the significance of the anterior spur formation sign.

STUDY DESIGN: Retrospective review. OBJECTIVE: To analyze the changes of fusion process and radiological parameters during the postoperative period after anterior cervical discectomy and fusion with cage and plate construct (ACDF-CPC). SUMMARY OF BACKGROUND DATA: Because of its well-reported efficacy, plate augmentation has been performed to avoid the various complications associated with the cage-alone procedure. The radiological changes at the fusion site after ACDF-CPC have yet to be fully explored. METHODS: Seventy-eight patients (122 fusion sites) who underwent ACDF-CPC were observed at 6 weeks and at 3, 6, 12, and 24 months postoperatively. Fusion status was classified into 3 categories: Type I (pseudoarthrosis), Type II (borderline), and Type III (fusion). Changes at the fusion site were described through radiological parameters at each follow-up time point. In addition, the ability of the radiological parameters to predict fusion rates was analyzed. RESULTS: The fusion process after ACDF-CPC progresses slower when compared with the standard procedure utilizing autograft. Fusion between bone graft chips begins at 6 weeks post surgery. At 3 months, initial bone bridging between graft and host bones begins to form. Anterior spur formation occurs at 3 to 6 months, and "kissing" lesions form at 6 to 12 months. Bony incorporation is achieved at 1 to 2 years. Persistent or newly developed Type I at the 1-year follow-up exhibited significantly higher pseudoarthrosis rates in comparison with rates determined at the 3- and 6-month time points. Among 29 subsidence cases, 9 of the 16 (56.3%) cases that exhibited anterior spur formation eventually achieved fusion, whereas 2 of the 13 (15.4%) cases that did not exhibit anterior spur formation eventually achieved fusion. In cases that demonstrated anterior spur formation, the fusion rate was significantly higher than in cases without it (P = 0.016). CONCLUSION: The fusion process after ACDF-CPC progresses slower than the standard procedure utilizing autograft. Cage subsidence of greater than 2 mm, a radiolucent defect, or a halo sign are poor prognostic signs indicating a high probability for pseudoarthrosis when detected radiographically after 1 year postoperatively. The anterior spur formation sign and "kissing" lesion, on the contrary, represent signs for eventual successful fusion.

Plate augmentation in anterior cervical discectomy and fusion with cage for degenerative cervical spinal disorders.

Anterior cervical discectomy and fusion (ACDF) with cage alone (ACDF-C) is associated with a significant incidence of subsidence, local kyphosis, and migration. The use of concurrent plate augmentation may decrease the incidence of these complications while improving the fusion rate. The purpose of the study is to present our results with ACDF with cage and plate augmentation (ACDF-CPA) and to compare these results to previous reports of outcomes following ACDF-C. We evaluated the radiologic and clinical parameters of 83 patients (266 fusion sites) who had an ACDF-CPA between March 2002 and May 2006. Radiologic parameters included fusion rate, fusion time, fusion type, site of pseudoarthrosis and rate and degree of subsidence. Clinical parameters included complications and overall outcomes assessed with Robinson's criteria; 79 of 83 patients showed bony fusion (95.1%) at last follow-up postoperatively, and there was no significant difference in fusion rate between the number of fusion levels. Type I (pseudoarthrosis) was noticed in 9 patients (12 fusion sites), type II in 14 (19 fusion sites), and type III in 60 (235 fusion sites). Five type I and all type II fusions converged into type III by the last follow-up; 76 of 83 patients (91.6%) experienced good clinical outcomes. Pseudoarthrosis occurred more commonly in more proximal locations, and the subsidence rate was significantly greater in two-level fusions when compared with single-level fusions (P = 0.046). There were four metal-related complications. Plate augmentation in one- or two-level anterior cervical fusions for degenerative cervical spine disorders may improve fusion rates and reduce subsidence and complication rates, resulting in improved clinical outcomes.

The efficacy of plate construct augmentation versus cage alone in anterior cervical fusion.

STUDY DESIGN.: Retrospective study. OBJECTIVE.: To compare the efficacy of anterior cervical discectomy and fusion with cage alone (ACDF-CA) with cage and plate construct (ACDF-CPC) in regards to fusion rate, radiologic and clinical outcomes. SUMMARY OF BACKGROUND DATA.: ACDF-CA has shown good results; however, debate exists regarding the high rate of complications such as pseudarthrosis, subsidence, and local kyphosis. In an attempt to avoid these complications, the authors have performed ACDF with cage and plate construct (ACDF-CPC). METHODS.: A total of 78 consecutive patients who underwent 1- or 2-level ACDF-CA or ACDF-CPC suffering from cervical radiculopathy were divided into 2 groups; Group A (n = 38) underwent ACDF-CA; Group B (n = 40) underwent ACDF-CPC. Fusion rate, segmental kyphosis, disc height, and subsidence rate were assessed by radiographs. Clinical outcomes were assessed using Robinson criteria. RESULTS.: Solid fusion was achieved in 78.9% (30/38) of subjects in group A compared to 97.5% (39/40) of subjects in group B (P = 0.01). Segmental kyphosis was noted in 42.1% (16/38) in group A compared with 10% (4/40) in group B (P < 0.01). There was a significant decrease in disc height in group A compared to group B (P < 0.05). Subsidence occurred in 32.3% (19/59 levels) of group A compared with 9.7% (6/62 levels) of group B (P < 0.01). Clinical outcomes were similar for both treatment groups. The pseudarthrosis rate in group A was higher than that in group B (P = 0.01). Revision surgery was required in 10.5% (4/38) of group A, whereas none of group B required reoperation (P < 0.01). CONCLUSION.: The use of cage and plate construct in 1- or 2-level ACDF results in a more lordotic alignment, an increased disc height, a higher fusion rate, a lower subsidence rate, and a lower complication rate than that of cage alone; however, there is no significant difference in clinical outcome between groups.

Mechanism of glutamate-induced neurotoxicity in HT22 mouse hippocampal cells.

Glutamate is an endogenous excitatory neurotransmitter. At high concentrations, it is neurotoxic and contributes to the development of certain neurodegenerative diseases. There is considerable controversy in the literature with regard to whether glutamate-induced cell death in cultured HT22 cells (an immortalized mouse hippocampal cell line) is apoptosis, necrosis, or a new form of cell death. The present study focused on investigating the mechanism of glutamate-induced cell death. We found that glutamate induced, in a time-dependent manner, both necrosis and apoptosis in HT22 cells. At relatively early time points (8-12 h), glutamate induced mostly necrosis, whereas at late time points (16-24 h), it induced mainly apoptosis. Glutamate-induced mitochondrial oxidative stress and dysfunction were crucial early events required for the induction of apoptosis through the release of the mitochondrial apoptosis-inducing factor (AIF), which catalyzed DNA fragmentation (an ATP-independent process). Glutamate-induced cell death proceeded independently of the Bcl-2 family proteins and caspase activation. The lack of caspase activation likely resulted from the lack of intracellular ATP when the mitochondrial functions were rapidly disrupted by the mitochondrial oxidative stress. In addition, it was observed that activation of JNK, p38, and ERK signaling molecules was also involved in the induction of apoptosis by glutamate. In conclusion, glutamate-induced apoptosis is AIF-dependent but caspase-independent, and is accompanied by DNA ladder formation but not chromatin condensation.

Suppression of the alpha-isoform of class II phosphoinositide 3-kinase gene expression leads to apoptotic cell death.

Phosphoinositide 3-kinases (PI3Ks) have known to be key enzymes activating intracellular signaling molecules when a number of growth factors bind to their cell surface receptors. PI3Ks are divided into three classes (I, II, and III) and enzymes of each class have different tissue-specificities and physiological functions. Class II PI3Ks consist of three isoforms (alpha,beta,gamma). Although the alpha-isoform (PI3K-C2alpha) is considered ubiquitous and preferentially activated by insulin rather than the beta-isoform, the physiological significance of PI3K-C2alpha is poorly understood. The present study aimed to determine whether PI3K-C2alpha is associated with the suppression of apoptotic cell death. Different sense- and antisense oligonucleotides (ODNs) were synthesized based on the sequence of C2 domain of PI3K-C2alpha gene. Transfection of CHO-IR cells with two different antisense ODNs clearly reduced the protein content as well as mRNA levels of PI3K-C2alpha whereas neither the nonspecific mock- nor sense ODNs affected. The decrease of PI3K-C2alpha gene expression was paralleled by cellular changes indicating apoptotic cell death such as nuclear condensation, formation of apoptotic bodies, and DNA fragmentation. PI3K-C2alpha mRNA levels were also reduced when cells were incubated in growth factor-deficient medium. Supplementing growth factors (serum or insulin) into medium lead to an increase of PI3K-C2alpha mRNA levels. This finding strongly suggests that PI3K-C2alpha is a crucial survival factor.