Deep learning-based diagnosis of lung cancer using a nationwide respiratory cytology image set: improving accuracy and inter-observer variability.

Deep learning (DL)-based image analysis has recently seen widespread application in digital pathology. Recent studies utilizing DL in cytopathology have shown promising results, however, the development of DL models for respiratory specimens is limited. In this study, we designed a DL model to improve lung cancer diagnosis accuracy using cytological images from the respiratory tract. This retrospective, multicenter study used digital cytology images of respiratory specimens from a quality-controlled national dataset collected from over 200 institutions. The image processing involves generating extended z-stack images to reduce the phase difference of cell clusters, color normalizing, and cropping image patches to 256 × 256 pixels. The accuracy of diagnosing lung cancer in humans from image patches before and after receiving AI assistance was compared. 30,590 image patches (1,273 whole slide images [WSIs]) were divided into 27,362 (1,146 WSIs) for training, 2,928 (126 WSIs) for validation, and 1,272 (1,272 WSIs) for testing. The Densenet121 model, which showed the best performance among six convolutional neural network models, was used for analysis. The results of sensitivity, specificity, and accuracy were 95.9%, 98.2%, and 96.9% respectively, outperforming the average of three experienced pathologists. The accuracy of pathologists after receiving AI assistance improved from 82.9% to 95.9%, and the inter-rater agreement of Fleiss' Kappa value was improved from 0.553 to 0.908. In conclusion, this study demonstrated that a DL model was effective in diagnosing lung cancer in respiratory cytology. By increasing diagnostic accuracy and reducing inter-observer variability, AI has the potential to enhance the diagnostic capabilities of pathologists.

Changes in retro-odontoid mass after upper cervical spine surgery.

A non-neoplastic mass posterior to the dens is termed a retro-odontoid mass (R-OM). This retrospective study evaluated radiographic and clinical outcomes and R-OM changes after upper cervical spine surgery. This study included 69 patients who underwent upper cervical spine surgery, including atlantoaxial fusion, occipitocervical fusion, or decompression. All patients underwent preoperative magnetic resonance imaging (MRI). Six-month follow-up MRI examinations were performed in 30 patients who had preoperative R-OMs. Radiographic outcomes of the anterior and posterior atlantodental intervals were measured using X-rays and computed tomography. The R-OM and space available for the cord (SAC) were measured using MRI. Clinical outcomes were evaluated using neck and arm pain visual analog scales, the Japanese Orthopedic Association score, the neck disability index, and the patient-reported subjective improvement rate. The anterior atlantodental interval decreased, while the posterior atlantodental interval and SAC increased postoperatively. Among the clinical outcomes, the neck and arm pain and the neck disability index decreased postoperatively, while the Japanese Orthopedic Association score increased. All clinical and radiographic outcomes improved postoperatively. The R-OM either decreased in size or disappeared after fusion surgery in all cases, except in one patient who underwent decompression surgery. In conclusion, stabilization through fusion surgery is essential for treating R-OM.

Direct Internal Fixation for Unstable Atlas Fractures.

PURPOSE: To investigate the radiologic and clinical outcomes of direct internal fixation for unstable atlas fractures. MATERIALS AND METHODS: This retrospective study included 12 patients with unstable atlas fractures surgically treated using C1 lateral mass screws, rods, and transverse connector constructs. Nine lateral mass fractures with transverse atlantal ligament (TAL) avulsion injury and three 4-part fractures with TAL injury (two avulsion injuries, one TAL substance tear) were treated. Radiologic outcomes included the anterior atlantodental interval (AADI) in flexion and extension cervical spine lateral radiographs at 6 months and 1 year after treatment. CT was also performed to visualize bony healing of the atlas at 6 months and 1 year. Visual Analog Scale (VAS) scores for neck pain, Neck Disability Index (NDI) values, and cervical range of motion (flexion, extension, and rotation) were recorded at 6 months after surgery. RESULTS: The mean postoperative extension and flexion AADIs were 3.79±1.56 (mean±SD) and 3.13±1.01 mm, respectively. Then mean AADI was 3.42±1.34 and 3.33±1.24 mm at 6 months and 1 year after surgery, respectively. At 1 year after surgery, 11 patients showed bony healing of the atlas on CT images. Only one patient underwent revision surgery 8 months after primary surgery due to nonunion and instability findings. The mean VAS score for neck pain was 0.92±0.99, and the mean NDI value was 8.08±5.70. CONCLUSION: C1 motion-preserving direct internal fixation technique results in good reduction and stabilization of unstable atlas fractures. This technique allows for the preservation of craniocervical and atlantoaxial motion.

Nonclinical Safety Pharmacology Study of the Herbal Product HAD-B1.

HAD-B1 is a Korean herbal formula designed to treat solid tumors, and through cell experiments, it has proven to have an anticancer effect. The current study aims to test the safety of HAD-B1. This experiment is under the regulation of ICH. In order to find if HAD-B1 has any effect on the CNS, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally administered to male and female rats once. To discover any effect on the respiratory system, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally given to male rats followed by measuring the respiratory rate, tidal volume, and minute respiratory volume. To assess the possibility of a delayed QT period as a result of the drug administration, hERG analysis was conducted at 0, 0.1, 0.3, and 1 µg/ml. To assess any effect on the cardiovascular system, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally given to male beagle dogs once followed by temperature, blood pressure, ECG, and heart rate analyses. There were no clinically significant changes in both male and female rats on assessing any effects on the CNS. There were no clinically significant changes in male rats' respiratory assessment. There were no clinically significant changes in hERG analysis results. There were no clinically significant changes in the cardiovascular system of male beagle dogs. Our results demonstrate that HAD-B1 is a safe herbal formula that does not have a clinically significant effect on the CNS, respiratory, and cardiovascular systems.

Perfluorooctane sulfonate and bisphenol A induce a similar level of mast cell activation via a common signaling pathway, Fyn-Lyn-Syk activation.

Perfluoroalkyl compounds (PFCs) as food contaminants are widely distributed persistent organic pollutants (POPs) and have been suggested to induce immune dysfunction. However, their effects on immune function are not conclusive. Mast cells play a central role in allergic and non-allergic inflammatory responses. Therefore, we have examined the effects of PFCs (PFHxS, PFOA, PFOS) on mast cell-mediated inflammatory responses using in vitro mouse bone marrow-derived mast cells (BMMCs) and human mast cells (HMC-1) and in vivo mice model. The effects of PFCs were compared with those of bisphenol A (BPA), a well-studied environmental pollutant. Among PFCs tested, PFOS had the highest effects. Both PFOS and BPA increased degranulation and production of inflammatory eicosanoids in mast cells at a similar level, which subsequently led to increased skin edema and serum LTC4 and PGD2 in mice. Both PFOS and BPA increased not only downstream signaling (PLCγ1, AKT, ERK), but also upstream signaling (Fyn, Lyn, Syk/LAT) in mast cells. Taken together, PFOS and BPA induce mast cell-mediated inflammatory responses via a common signaling pathways. Our results may help establish the scientific basis for understanding the etiology of mast cell-mediated inflammatory responses and improve the immune dysfunction risk assessment for emerging POPs such as PFCs.

Transient fixation of L4 vertebra preserves lumbar motion and function in Lenke Type 5C and 6C scoliosis.

This study investigated the efficacy of a novel surgical method that relies on the transient fixation of L4 in Lenke Type 5C and 6C adolescent idiopathic scoliosis. Thirty-six transient surgically treated L4 fixation patients were retrospectively evaluated. The first surgery involved mechanical correction of scoliosis; the lowest instrumented vertebra (LIV) was L4. After an average of 1.3 years (range, 0.3-3.4), the second surgery to remove transient L4 pedicle screws was performed. Radiographic parameters and SRS-22 scores were measured. Cobb's angle, coronal balance, LIV tilting angle, and LIV coronal disc angle clearly improved after the first surgery (p < 0.01). After the second surgery, the corrected Cobb angle (p = 0.446) and coronal balance were maintained (p = 0.271). Although L3/S1 lumbar lordosis decreased after the first surgery (p < 0.01), after removal of transient L4 pedicle screws, it recovered slightly (p = 0.03). Similarly, the preoperative L3/4 lateral disc mobility eventually recovered after transient L4 screw removal (p < 0.01). The function domain of the SRS-22 showed better scores after removal of transient L4 screws (p = 0.04). L4 transient fixation surgery is beneficial for Lenke Type 5C and 6C scolioses that do not fully satisfy LIV (L3) criteria. It preserves L3/4 disc motion, increases functional outcomes, and maintains spinal correction and coronal balance.

Acrylamide and its metabolite induce neurotoxicity via modulation of protein kinase C and AMP-activated protein kinase pathways.

Acrylamide is known as a neurotoxicant found in commonly consumed food as well as in human body. However, the underlying mechanisms involved in neurotoxicity by acrylamide and its metabolite, glycidamide remain largely unknown. In this study, we have examined the interplay between CYP2E1, AMPK, ERK and PKC in acrylamide-induced neurotoxicity associated with autophagy in PC12 cells. Acrylamide-induced cell death was mediated by CYP2E1 expression and the activation of ERK, PKC-ɑ and PKC-δ, whereas AMPK knockdown exacerbated the acrylamide-induced neurotoxic effects. PKC-ɑ, but not PKC-δ, plays an upstream regulator of ERK and AMPK. Moreover, AMPK activation suppressed ERK, and CYP2E1 and AMPK bilaterally inhibit each other. Furthermore, acrylamide increased autophagy with impaired autophagic flux, evidenced by the increased beclin-1, LC3-II and p62 protein. Acrylamide-induced neuronal death was ameliorated by 3-methyladenine, an autophagy inhibitor, whereas neuronal death was exacerbated by chloroquine, a lysosomal inhibitor. Interestingly, PKC-δ siRNA, but not PKC-ɑ siRNA, dramatically reduced acrylamide-induced beclin-1 and LC3-II levels, whereas AMPK siRNA further increased beclin-1, LC3-II and p62 protein levels. Glycidamide, a major metabolite, mimicked acrylamide only with a higher potency. Taken together, acrylamide- and glycidamide-induced neurotoxicity may involve cytotoxic autophagy, which is mediated by interplay between PKCs and AMPK pathways.

Lumbar Spinal Stenosis: Pathophysiology and Treatment Principle: A Narrative Review.

Patients with lumbar spinal stenosis may exhibit symptoms such as back pain, radiating pain, and neurogenic claudication. Although long-term outcome of treatments manifests similar results for both nonsurgical and surgical treatments, positive effects such as short-term improvement in symptoms and decreased fall risk may be expected with surgery. Surgical treatment is basically decompression, and a combination of treatments can be added depending on the degree of decompression and the accompanying instability. Recently, minimally invasive surgery has been found to result in excellent outcomes in the treatment of lumbar spinal stenosis. Therefore, better treatment effects can be anticipated with an approach aimed at understanding the overall pathophysiology and treatment methods of lumbar spinal stenosis.

Prevalence of Gastrointestinal and Cardiovascular Risk in Patients with Degenerative Lumbar Spinal Disease.

BACKGROUND: Limited information is available about the proportion of patients with degenerative lumbar spinal disease (DLSD) who have gastrointestinal (GI) and cardiovascular (CV) risk factors. Many DLSD patients are prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) that are known to carry risks to the GI and CV systems by increasing GI bleeding and thromboembolic events. This study aimed to measure the prevalence of GI and CV risk in patients with DLSD and to ascertain whether the prescription of NSAIDs is in line with current guidelines. METHODS: This study included 153 patients with symptomatic DLSD who were planning to undergo lumbar spinal surgery. The GI profile was checked using the GI Standardized Calculator of Risk for Event system and CV risk was evaluated using the presence of metabolic syndrome. The conformity of the prescription of NSAIDs was investigated according to the recommendations in current guidelines. RESULTS: More than half of the patients (59.5%) had high or very high GI risk, and 66% of the patients were diagnosed with metabolic syndrome, which corresponds with CV risk. The rate of simultaneous GI and CV risk was 40.5% (n = 62 / 153; gastrointestinal Standardized Calculator of Risk for Event, > high and metabolic syndrome, yes). The actual prescription of NSAIDs was not in accordance with current guidelines. CONCLUSIONS: Two out of 3 patients had GI or CV risk factors, and approximately 40% of patients had both. Detailed assessment of GI and CV risk in patients with DLSD by using effective evaluation tools is mandatory for optimal medical treatment.

Generative Model for Proposing Drug Candidates Satisfying Anticancer Properties Using a Conditional Variational Autoencoder.

Deep learning-based molecular generative models have successfully identified drug candidates with desired properties against biological targets of interest. However, syntactically invalid molecules generated from a deep learning-generated model hinder the model from being applied to drug discovery. Herein, we propose a conditional variational autoencoder (CVAE) as a generative model to propose drug candidates with the desired property outside a data set range. We train the CVAE using molecular fingerprints and corresponding GI50 (inhibition of growth by 50%) results for breast cancer cell lines instead of training with various physical properties for each molecule together. We confirm that the generated fingerprints, not included in the training data set, represent the desired property using the CVAE model. In addition, our method can be used as a query expansion method for searching databases because fingerprints generated using our method can be regarded as expanded queries.

Hand grip strength as a surrogate marker for postoperative changes in spinopelvic alignment in patients with lumbar spinal stenosis.

There are a few studies on the postoperative changes in sagittal alignment and corresponding factors, including hand grip strength (HGS) and muscle performance tests for lumbar spinal stenosis (LSS). Thus, we aimed to determine whether HGS can be a surrogate marker for global sagittal alignment changes after decompression with fusion surgery for LSS. This retrospective observational study included 91 patients who underwent spine fusion surgery for LSS. Radiological spinopelvic parameters, including sagittal vertical axis (SVA), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), global tilt (GT), and T1 pelvic angle (T1PA), were analyzed preoperatively and 1 year after posterior decompression and fusion surgery. To assess muscle performance, the 6-m walk (SMT), timed up and go (TUGT), and sit-to-stand (STS) tests were conducted. The relationship between HGS and postoperative SVA was examined through multiple linear regression analysis. Additionally, the relationship between HGS and preoperative/postoperative radiologic spinopelvic parameters and muscle performance test results was analyzed through Pearson's correlation. HGS was significantly correlated with age, preoperative and postoperative SVA, and the muscle performance tests. Furthermore, HGS was a factor that can significantly influence postoperative SVA changes in multiple linear regression analyses. Therefore, HGS may be a good predictor of postoperative SVA change.

Hand grip strength can predict clinical outcomes and risk of falls after decompression and instrumented posterolateral fusion for lumbar spinal stenosis.

BACKGROUND CONTEXT: There has been limited research on the association between hand grip strength (HGS) as one of the diagnostic criteria for sarcopenia and surgical outcomes of lumbar spinal stenosis (LSS). PURPOSE: We aimed to determine the effect of HGS on surgical outcomes and risk of fall in patients with LSS. STUDY DESIGN: This is a retrospective observational study. PATIENT SAMPLE: We included 200 patients who underwent spinal surgery for LSS. OUTCOME MEASURES: We recorded clinical outcome parameters, including Oswestry Disability Index (ODI), Euro-QOL (EQ-5D), and visual analog scale (VAS) scores for back or leg pain. To assess the risk of fall we used HGS and four functional mobility tests (alternative step test, six-meter walk test, timed up and go test, sit-to-stand test). MATERIALS AND METHODS: ODI, EQ-5D, and VAS scores for back and leg pain were assessed preoperatively and 1 year after surgery. The four functional mobility tests were assessed at each time point during the 1-year follow-up period to assess the risk of fall in patients with LSS. We divided the patient cohort according to sex and allocated them into two different groups based on HGS: high HGS (≥26 kg for men, n=26; ≥18 kg for women, n=35), and low HGS (<26 kg for men, n=48; <18 kg for women, n=91). The pre- and postoperative ODI, EQ-5D, and VAS scores for back and leg pain, as well as the functional mobility test results, and demographic data were compared between the two groups using independent t tests. Correlations between HGS and clinical outcome parameters were analyzed using Pearson correlation. RESULTS: In women and men, HGS correlated with the preoperative/postoperative ODI (r1=-0.217/r2=-0.345 in women, and r1=-0.384/r2=-0.411 in men) and EQ-5D scores (r1=0.190/r2=0.309 in women, and r1=0.373/r2=0.467 in men). HGS also correlated with the four postoperative results for the functional mobility tests: alternative step test (r=-0.238 in women, r=-0.431 in men), six-meter walk test (r=-0.232 in women, r=-0.282 in men), timed up and go test (r=-0.285 in women, r=-0.359 in men), and sit-to-stand test (r=-0.238 in women, r=-0.251 in men). The preoperative and postoperative ODI and EQ-5D scores in the high HGS group were superior to those in the low HGS group. Among the four functional mobility tests, preoperative and postoperative six-meter walk test results showed improvements in the high HGS group. CONCLUSIONS: Considering the multifactorial nature of falls, HGS may be a useful surrogate marker for predicting the risk of falls and clinical outcomes in patients with LSS.

Comparison of survival analysis between surgical and non-surgical treatments in Duchenne muscular dystrophy scoliosis.

BACKGROUND CONTEXT: There are still controversies about the effects of spinal surgeries for Duchenne muscular dystrophy (DMD) scoliosis on functional outcome, respiratory function, and the survival rate. PURPOSE: The purpose of this retrospective investigation was to compare the clinical course over time between the patients who were treated surgically and those who were treated nonsurgically. Through this comparison, we tried to determine how surgical treatment could affect the functional status, pulmonary function, and survival rate in patients with DMD scoliosis. STUDY DESIGN/SETTING: Single-center retrospective cohort study. PATIENT SAMPLE: We reviewed the clinical data of 199 male patients with DMD scoliosis who were followed up at our center for an average of 6.4 years between 2003 and 2017. OUTCOME MEASURES: The basic radiologic parameters evaluated include the Cobb angle and pelvic obliquity on a whole spine X-ray. Further, the Swinyard scale for functional status, forced vital capacity (FVC) for respiratory function, and mortality were compared between the surgical group and nonsurgical group. METHODS: The radiologic parameters and Swinyard scale stage were compared between the surgical group and nonsurgical group at baseline and 2, 5, and 10 years. For the FVC, serial changes every year were investigated in both groups. Mortality was surveyed between the surgical group and nonsurgical group. RESULTS: Of the 199 patients, 99 patients underwent the instrumented spinal fusion surgery and 100 patients in the nonsurgical group opted for conservative management. Radiologic results of the two groups were not different at baseline, but during the follow-up periods, the surgical group demonstrated better Cobb angles and pelvic obliquities. The surgical group showed a better functional status than did the nonsurgical group (6.7±0.9 versus [vs.] 7.2±0.7, p<.001). These functional differences between the groups were continuously observed during the follow-up period. Similarly, the FVC at baseline was higher in the surgical group than in the nonsurgical group (1005.7±421.4 mL vs. 787.3±574.1 mL, p=.005). Although FVC in the nonsurgical group consistently decreased during the follow-up (4.8% decrease/year), FVC in the surgical group increased up to the 2-year follow-up period compared with the baseline value and decreased during the follow-up period (2.8% decrease/year). Mortality was higher in the nonsurgical group than in the surgical group (n=22/100, 22.0% vs. n=8/99, 8.1%; p<.001) during an average follow-up duration of 6.4 years. Mean survival was longer in the surgical group than in the nonsurgical group (12.2 years vs. 8.3 years, hazard ratio=2.43, p=.02). CONCLUSIONS: Spinal surgery for DMD scoliosis improved the FVC for approximately 2 years postoperatively compared to non-surgical treatment. The surgical group had a better functional status and FVC at baseline than the non-surgical group. The positive effect of surgical treatment on the FVC is owing to scoliosis correction, which delayed the decrease of FVC and consequently extended the survival rate of the patients with DMD scoliosis.

The Effects of Anterior Cruciate Ligament Reconstruction on Individual Quadriceps Muscle Thickness and Circulating Biomarkers.

Anterior cruciate ligament reconstruction (ACLR) frequently results in quadriceps atrophy. The present study investigated the effect of ACLR on the muscle thickness of the different constituent muscles of the quadriceps and circulating biomarkers related to muscle atrophy and hypertrophy. Fourteen subjects underwent anterior cruciate ligament reconstruction following injury. Quadriceps muscle thicknesses were measured using ultrasound, and circulating biomarkers in the blood were measured using enzyme-linked immunosorbent assays (ELISAs) at the preoperative visit (PRE) and at two postoperative visits (PO1, PO2) in the early stages post-surgery. Differences between time points were analyzed using one-way repeated measures analysis of variance (ANOVA) tests. The most important finding was that severe muscle atrophy occurred in the vastus intermedius (VI) after ACLR (PRE: 20.45 ± 6.82 mm, PO1: 16.05 ± 6.13 mm, PO2: 13.18 ± 4.7 mm, F = 59.0, p < 0.001). Furthermore, the myostatin level was slightly increased, and IGF-1 was significantly reduced throughout the entire period. Therefore, we suggest that inducing selective hypertrophy in the vastus intermedius during the process of rehabilitation would be important for athletes and individuals who engage in explosive sports. Moreover, inhibiting myostatin level increases and maintaining IGF-1 levels in the early phase of recovery after ACLR to prevent muscle atrophy may provide a pharmaceutical option for rehabilitation after anterior cruciate ligament injury.

What is a Right Distal Fusion Level for Prevention of Sagittal Imbalance in Multilevel Posterior Cervical Spine Surgery: C7 or T1?

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To evaluate the sagittal alignment and T1 slope after multilevel posterior cervical fusion surgery depending on the distal fusion level; C7 or T1, and find out the appropriate distal fusion level. SUMMARY OF BACKGROUND DATA: The sagittal balance of the cervical spine is known to be affected by cervical lordosis and T1 slope. However, T1 slope is not a constant parameter that can be frequently changed after the surgery. Furthermore, useful studies to help guide surgeons in decision-making as to the most appropriate distal level of fusion for cervical sagittal balance are very limited. MATERIALS AND METHODS: From 2014 to 2015, 50 patients who underwent multilevel posterior cervical fusion surgery were evaluated and followed up for >2 years. Group 1 was composed of 29 patients whose distal fusion level was C7. Group 2 was composed of 21 patients whose distal fusion level was T1. C1-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1 slope were measured on preoperative and the last follow-up. RESULTS: In group 1, C2-C7 SVA (23.1→30.4 mm, P=0.043) was worsened, and T1 slope (22.3→32.9 degrees, P=0.001) was increased after the surgery. In group 2, no significant change occurred in C2-C7 SVA after the surgery (25.3 →23.6 mm, P=0.648). The last follow-up T1 slope was similar with preoperative T1 slope (22.7→21.8 degrees, P=0.04) in group 2. CONCLUSIONS: This study showed that sagittal alignment became worse after the multilevel posterior cervical surgery when distal fusion level was stopped at C7, which was associated with increase of T1 slope. However, when we extended the distal fusion level to T1, T1 slope was not changed after the surgery. Therefore, sagittal alignment was maintained after the surgery. On the basis of the results of this study, we recommend distal fusion extends to T1. LEVEL OF EVIDENCE: Level III.

Pamidronate Down-regulates Tumor Necrosis Factor-alpha Induced Matrix Metalloproteinases Expression in Human Intervertebral Disc Cells.

BACKGROUND: N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. METHODS: Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10(-12), 10(-10), 10(-8), and 10(-6) M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. RESULTS: Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. CONCLUSIONS: Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression.

First-Order Mathematical Correlation Between Damping and Resonance Frequency Evaluating the Bone-Implant Interface.

PURPOSE: Various advanced technologies have been designed to estimate dental implant stability, including insertion torque, implant damping using the Periotest, and resonance frequency analysis expressed in implant stability quotient units. This study aimed to establish the relationship between the estimates for these three techniques. MATERIALS AND METHODS: Bovine cortical bone blocks were trimmed to square shapes of precisely controlled thickness and density. Thereafter, 4-mm-diameter × 10-mm-long implants were placed in the bone blocks using 30-, 45-, and 60-Ncm insertion torques. Implant damping and resonance frequency analysis were conducted at four angles for each implant. Spearman correlation coefficients were calculated to examine the relationship between insertion torque, resonance frequency analysis, and implant damping measured values. RESULTS: Resonance frequency analysis and implant damping estimates exhibited a strong inverse correlation (r = -0.98, P < .001). A linear equation was formulated: Periotest value = 15.54 + (-0.26 × implant stability quotient). Implant damping and resonance frequency estimates revealed a weak correlation with insertion torque (P < .05). CONCLUSION: This study mathematically defined a linear correlation between implant damping and resonance frequency estimates, thereby providing a guide for clinicians when deciding the loading time for dental implants using the implant damping or resonance frequency estimates.

Spinal sagittal balance status affects postoperative actual falls and quality of life after decompression and fusion in-situ surgery in patients with lumbar spinal stenosis.

OBJECTIVES: It has been reported that good spinal sagittal alignment reduces the risk of fall and positive sagittal balance is the radiographic parameter that is most highly correlated with adverse health outcomes. However, no reports have demonstrated a change in risk of falling in patients with lumbar spinal stenosis (LSS) according to sagittal balance status. PATIENTS AND METHODS: From September 2013 to October 2014, 141 patients who underwent lumbar spine surgery, including decompression and fusion in-situ for LSS, were enrolled in this study. Based on sagittal balance status, patients were divided into sagittal balance (SB) and sagittal imbalance (SI) groups. Four functional mobility tests were used to evaluate the risk of falling, and a fall diary, Oswestry disability index (ODI), and the Euro-QoL 5D(EQ-5D) visual analogue scale (VAS) were utilized to assess clinical improvement. RESULTS: The mean patient age was 70.1 years in the SB group (N=46) and 70.9 years in the SI group (N=95) (not significant). The mean C7PL was 7.9mm in the SB group and 66.1mm in the SI group preoperatively (p<0.05). Among the four functional tests, only postoperative SMT and STS improved significantly in the SB group (p<0.05). Patients in the SI group showed significantly improved scores for all four functional tests during postoperative follow-up (p<0.05), but their performance was still worse than patients in the SB group. Average number of falls per individual during the follow-up period was 1.1±2.5 in the SB group and 1.9±3.2 in the SI group (p<0.05). There was a significant difference in the distribution of non-fallers and fallers (single and multiple fallers) between the two groups postoperatively(p<0.05). ODI and the EQ-5D VAS showed greater improvement in the SB group than the SI group. Multiple regression analysis revealed that sagittal balance during follow-up significantly affected ODI, EQ-VAS, functional mobility tests. (p<0.05). CONCLUSION: Therefore, when fusion surgery is planned in patients with LSS, careful consideration of sagittal balance status might be important to attain better surgical and functional outcomes and decrease the incidence of actual falls after surgical treatment.

Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway.

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.

AMP-activated protein kinase is involved in perfluorohexanesulfonate-induced apoptosis of neuronal cells.

Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds (PFCs), has been used in a variety of industrial and consumer applications and detected in serum in the general population. This raised a concern over its possible detrimental health effects, including neurotoxic effects. We have previously shown that PFHxS induced neuronal apoptosis via the NMDA receptor-mediated extracellular signal-regulated kinase (ERK) pathway. Recently, it has been reported that AMP-activated protein kinase (AMPK) acts as a key signal molecule in neuronal excitotoxicity as well as providing a neuroprotective function. In the present study, we have examined the involvement of AMPK in PFHxS-induced neuronal apoptosis using neuronal differentiated PC12 cells. PFHxS induced significant increases in intracellular [Ca(2+)] via the NMDA receptor and the L-type voltage-gated calcium channel (L-VGCC). The inhibition of Ca(2+) loading by the NMDA receptor antagonist, MK801 and the L-VGCC blockers, nifedipine and diltiazem significantly reduced PFHxS-induced apoptosis. PFHxS induced sustained activation of AMPK and the inhibition of AMPK activation by compound C and AMPK siRNA significantly reduced PFHxS-induced caspase-3 activity. These results indicate the pro-apoptotic role of AMPK. The activation of AMPK was attenuated by MK801, nifedipine and diltiazem. However, the activation of AMPK was not affected by the ERK inhibitor, PD98059. Likewise, ERK activation was not affected by compound C but was substantially reduced by MK801, nifedipine or diltiazem. This suggests that the activation of AMPK and ERK is regulated by intracellular Ca(2+) loading in distinct pathways. Taken together, PFHxS-induced neuronal apoptosis is mediated by AMPK and ERK pathways, which are distinctly regulated by increased intracellular Ca(2+) via the NMDA receptor and L-VGCC.