Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues.

A concise synthesis of pareitropone by oxidative cyclization of a phenolic nitronate is delineated. The use of TMSOTf as an additive to promote the facile formation of a strained norcaradiene intermediate provides convenient access to highly condensed multicyclic tropones in high yields. This synthesis is modular, efficient, and scalable, highlighting the synthetic utility of radical anion coupling reactions in annulation reactions. This work is discussed in the context of total syntheses of the tropoloisoquinoline alkaloids. Also included are the preparation of several congeners and a brief description of their biological activities.

Surgical outcomes of two kinds of demineralized bone matrix putties/local autograft composites in instrumented posterolateral lumbar fusion.

BACKGROUND: This study aimed to assess the surgical outcomes of two kinds of demineralized bone matrix (DBM) putties/local autograft composites in instrumented posterolateral lumbar fusion (PLF). METHODS: Twenty-seven fusion segments of 19 patients, who underwent decompression and instrumented PLF for lumbar spinal stenosis or degenerative spondylolisthesis less than grade 1, were included in this study. The PLF mass consisted of different two kinds of DBMs (Grafton® and DBX®) and local autograft. Next, 7.5 cc of Grafton® DBM/local autograft composite was implanted on the left side, and the same amount of DBX® DBM/local autograft composite was implanted on the right side in the same patient. The PLF masses of 54 total sides (27 Grafton® sides and 27 DBX® sides) were assessed for fusion based on both flexion/extension lateral radiographs and computed tomography images at 12 and 24 months postoperatively. Clinical symptoms were also evaluated. RESULTS: At 12 months postoperatively, the fusion rates for the Grafton® and DBX® sides were 59.5 and 51.9%, respectively; the difference was not statistically significant (P = 0.425). At 24 months postoperatively, the fusion rates for the Grafton® and DBX® sides increased to 70.4 and 66.7%, respectively, but the difference was still not statistically significant (P = 0.574). Diabetes mellitus, smoking, and obesity (body mass index ≥25) negatively affected the fusion rate of both the Grafton® and DBX® sides. Visual analog scores for lower back pain and leg pain and Oswestry Disability Index were significantly improved after surgery (both, P < 0.01). No deep or superficial infections occurred postoperatively. No patients underwent revision surgery due to nonunion during follow-up. CONCLUSIONS: Our results suggest that two kinds of DBMs/local autograft composites might be considered as useful bone graft substitute in instrumented posterolateral fusion for lumbar spinal stenosis or degenerative spondylolisthesis less than grade 1.

15-year survivorship analysis of an interspinous device in surgery for single-level lumbar disc herniation.

BACKGROUND: Interspinous devices have been introduced as alternatives to decompression or fusion in surgery for degenerative lumbar diseases. This study aimed to investigate 15-year survivorship and risk factors for reoperation of a Device for Intervertebral Assisted Motion (DIAM) in surgery for 1-level lumbar disc herniation (LDH). METHODS: A total of 94 patients (54 men and 40 women) underwent discectomy and DIAM implantation for 1-level LDH, with a mean follow-up of 12.9 years (range, 6.3-15.3 years). The mean age was 46.2 years (range, 21-65 years). Sixty-two patients underwent DIAM implantation for L4-5, 27 for L5-6, and 5 for L3-4. Reoperations due to any reason associated with DIAM implantation level or adjacent levels were defined as failure and used as the end point of determining survivorship. RESULTS: During the 15-year follow-up, 8 patients (4 men and 4 women) underwent reoperation due to recurrence of LDH at the DIAM implantation level, a reoperation rate of 8.5%. The mean time to reoperation was 6.5 years (range, 0.8-13.9 years). Kaplan-Meier analysis showed a cumulative survival rate of the DIAM implantation of 97% at 5 years, 93% at 10 years, and 92% at 15 years after surgery; the cumulative reoperation rate of the DIAM implantation was 3% at 5 years, 7% at 10 years, and 8% at 15 years after surgery. Mean survival time was predicted to be 14.5 years (95% CI, 13.97-15.07). The log-rank test and Cox proportional hazard model showed that age, sex, and location did not significantly affect the reoperation rate of DIAM implantation. CONCLUSIONS: Our results showed that DIAM implantation significantly decreased reoperation rate for LDH in the 15-year survivorship analysis. We suggest that DIAM implantation could be considered a useful intermediate step procedure for LDH surgery. To the best of our knowledge, this is the longest follow-up study in which surgical outcomes of interspinous device surgery were reported.

Hyperacute onset of adjacent segment disease with dorsally migrated herniated nucleus pulposus causing cauda equina syndrome: a case report.

PURPOSE: To report the first case of hyperacute onset of adjacent segmental disease (ASD) with dorsally migrated herniated nucleus pulposus (HNP) causing cauda equina syndrome. METHODS: A 55-year-old female complained of lower back pain with radiating pain in both lower extremities that had not responded to conservative treatment over the previous six months. Plain radiographs and magnetic resonance imaging (MRI) findings revealed degenerative spondylolisthesis with spinal stenosis at L3-4, L4-5, and a slight bulging disc at L2-3. The patient underwent decompressive total laminectomy and posterior fusion at L3-4 and L4-5. The stenotic symptoms improved significantly after surgery, and she was then discharged on postoperative day 7. RESULTS: However, the patient visited the emergency department four days after discharge (postoperative day 11) complaining of sudden onset of bilateral lower extremity weakness and voiding and defecation difficulties. The follow-up MRI showed dorsally migrated huge HNP and a detached posterior longitudinal ligament (PLL) at L2-3, which was diagnosed as hyperacute onset of ASD causing cauda equina syndrome. The patient underwent an emergency second operation consisting of partial laminectomy at L2-3 with removal of the dorsally migrated huge HNP. After the second operation, the symptoms of cauda equina syndrome improved. One year after the second operation, the patient is doing well without recurrence of symptoms. CONCLUSIONS: Our case showed that hyperacute onset of ASD with dorsally migrated huge HNP can cause cauda equina syndrome, even within 2 weeks after lumbar fusion surgery. Therefore, a high index of suspicion, timely diagnosis, and surgical treatment are needed to avoid the catastrophic neurologic complications in similar extremely rare cases.

Cervical myelopathy due to subaxial calcium pyrophosphate dihydrate (CPPD) deposition with simultaneous asymptomatic crowned dens syndrome: two case reports.

BACKGROUND: There are few reports of cervical myelopathy caused by an attack of subaxial calcium pyrophosphate dihydrate (CPPD) deposition. Moreover, there has been no report on cervical myelopathy by subaxial CPPD deposition with simultaneous asymptomatic crowned dens syndrome (CDS) at the same time. CASE PRESENTATION: The first case was a 68-year-old male complaining of cervical myelopathic symptoms. Plain radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) findings revealed spinal cord compression by calcified round lesions at C4 as well as a calcified lesion behind the dens. The second case was a 77-year-old female complaining of cervical myelopathic symptoms. Plain radiographs, CT and MRI findings revealed spinal cord compression by calcified round lesions at C3 and C4 as well as a calcified lesion behind the dens. In both cases, we believed that the calcified lesion behind the dens was an asymptomatic lesion. Therefore, the first patient received decompressive laminectomy of C3 and C4, removal of calcified round lesions, and posterior fixation from C3 to C5 due to associated kyphosis. The second patient underwent decompressive laminectomy of C3 and C4 and removal of calcified round lesions. Microscopic examination under polarized light showed dark blue calcifications with rhomboid crystals that were positively birefringent. The findings were consistent with those of CPPD. CONCLUSIONS: This is the first study to report cervical myelopathy caused by subaxial CPPD deposition with simultaneous asymptomatic CDS. Surgical removal of the subaxial CPPD deposition alone achieved a satisfactory surgical outcome without recurrence.

The impact of COVID-19 pandemic on orthopaedic resident education: a nationwide survey study in South Korea.

PURPOSE: There have not been well-designed survey studies investigating the impact of the coronavirus disease 2019 (COVID-19) pandemic on orthopaedic resident education. METHODS: A 58-question, web-based survey was administered to orthopaedic residents in South Korea. A total of 229 orthopaedic residents from 43 hospitals completed the survey questionnaire. RESULTS: The average working time of 72.7 hours/week before the pandemic was decreased to 65.6 hours/week during the pandemic (p < 0.001). The time working in the operating room was significantly decreased during the pandemic, but not in the emergency centre and outpatient clinic. The education times for lecture and clinical case discussion were decreased during the pandemic (both, p < 0.001), respectively. While the use of traditional teaching methods was decreased, the use of online-based teaching methods was increased (p < 0.001). However, satisfaction level with online-based teaching methods was significantly lower compared with that of traditional teaching methods. The average working time exposed to the patients with COVID-19 was 9.7 hours/week. About 47.6% of orthopaedic residents experienced isolation or quarantine. The average score for quality of life, which was 68.9 out of 100 scores before the pandemic, decreased to 61.7 during the pandemic (p < 0.001). The most stressful factor for orthopaedic residents during the pandemic was family/relative health, followed by their own health and residency program. CONCLUSION: The COVID-19 pandemic had a significant impact on orthopaedic resident education in South Korea. Therefore, flexible and sustainable strategies are necessary to prepare for the future as well as the current pandemic situation.

Accelerated premature stress-induced senescence of young annulus fibrosus cells of rats by high glucose-induced oxidative stress.

PURPOSES: Diabetes mellitus (DM) is thought to be an important aetiological factor in intervertebral disc degeneration. A glucose-mediated increase of oxidative stress is a major causative factor in development of diseases associated with DM. The aim of this study was to investigate the effect of high glucose on mitochondrial damage, oxidative stress and senescence of young annulus fibrosus (AF) cells. METHODS: AF cells were isolated from four-week-old young rats, cultured, and placed in either 10 % FBS (normal control) or 10 % FBS plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days. We identified and quantified the mitochondrial damage and reactive oxygen species (ROS) (oxidative stress). We also identified and quantified the occurrence of senescence and telomerase activity. Finally, the expressions of proteins were determined related to replicative senescence (p53-p21-pRB) and stress-induced senescence (p16-pRB). RESULTS: Two high glucoses enhanced the mitochondrial damage in young rat AF cells, which resulted in an excessive generation of ROS in a dose- and time-dependent manner for one and three days compared to normal control. Two high glucose concentrations increased the occurrence of senescence of young AF cells in a dose- and time-dependent manner. Telomerase activity declined in a dose- and time-dependent manner. Both high glucose treatments increased the expressions of p16 and pRB proteins in young rat AF cells for one and three days. However, compared to normal control, the expressions of p53 and p21 proteins were decreased in young rat AF cells treated with both high glucoses for one and three days. CONCLUSIONS: The present study demonstrated that high glucose-induced oxidative stress accelerates premature stress-induced senescence in young rat AF cells in a dose- and time-dependent manner rather than replicative senescence. These results suggest that prevention of excessive generation of oxidative stress by strict blood glucose control could be important to prevent or to delay premature intervertebral disc degeneration in young patients with DM.

Artificial Intelligence-Assisted MRI Diagnosis in Lumbar Degenerative Disc Disease: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: Lumbar degenerative disc disease (DDD) poses a significant global health care challenge, with accurate diagnosis being difficult using conventional methods. Artificial intelligence (AI), particularly machine learning and deep learning, offers promising tools for improving diagnostic accuracy and workflow in lumbar DDD. This study aims to review AI-assisted magnetic resonance imaging (MRI) diagnosis in lumbar DDD and discuss current research for clinical use. METHODS: A systematic search of electronic databases identified studies on AI applications in MRI-based lumbar DDD diagnosis, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Search terms included combinations of "Artificial Intelligence," "Machine Learning," "Deep Learning," "Low Back Pain," "Lumbar," "Disc," "Degeneration," and "MRI," targeting studies in English from January 1, 2010, to January 1, 2024. Inclusion criteria encompassed experimental and observational studies in peer-reviewed journals. Data extraction focused on study characteristics, AI techniques, performance metrics, and diagnostic outcomes, with quality assessed using predefined criteria. RESULTS: Twenty studies met the inclusion criteria, employing various AI methodologies, including machine learning and deep learning, to diagnose lumbar DDD manifestations such as disc degeneration, herniation, and bulging. AI models consistently outperformed conventional methods in accuracy, sensitivity, and specificity, with performance metrics ranging from 71.5% to 99% across different diagnostic objectives. CONCLUSION: The algorithm model provides a structured framework for integrating AI into routine clinical practice, enhancing diagnostic precision and patient outcomes in lumbar DDD management. Further research and validation are needed to refine AI algorithms for real-world application in lumbar DDD diagnosis.

High glucose-induced oxidative stress promotes autophagy through mitochondrial damage in rat notochordal cells.

PURPOSE: Diabetes mellitus is associated with an increased risk of intervertebral disc degeneration (IDD). Reactive oxygen species (ROS), oxidative stressors, play a key role in autophagy of diabetes-associated diseases. Mitochondria are known to be the main source of endogenous ROS in most mammalian cell types. The authors therefore conducted the following study to evaluate the effects of high glucose concentrations on the induction of oxidative stress and autophagy through mitochondrial damage in rat notochordal cells. METHODS: Rat notochordal cells were isolated, cultured, and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. We identified and quantified the mitochondrial damage (mitochondrial transmembrane potential) and the generation of ROS and antioxidants (manganese superoxide dismutase [MnSOD] and catalase). We also investigated expressions and activities of autophagy markers (beclin-1, light chain3-I [LC3-I] and LC3-II, autophagy-related gene [Atg] 3, 5, 7, and 12). RESULTS: An enhanced disruption of mitochondrial transmembrane potential, which indicates mitochondrial damage, was identified in rat notochordal cells treated with both high glucose concentrations. Both high glucose concentrations increased production of ROS by rat notochordal cells in a dose- and time-dependent manner. The two high glucose solutions also enhanced rat notochordal cells' compensatory expressions of MnSOD and catalase in a dose- and time-dependent manner. The proautophagic effects of high glucose concentrations were manifested in the form of enhanced rat notochordal cells' expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose- and time-dependent manner. CONCLUSIONS: The findings from this study demonstrate that high glucose-induced oxidative stress promotes autophagy through mitochondrial damage of rat notochordal cells in a dose- and time-dependent manner. These results suggest that preventing the generation of oxidative stress might be a novel therapeutic target by which to prevent or to delay IDD in patients with diabetes mellitus.

Inhibitory Effect of Insulin Treatment on Apoptosis of Intervertebral Disc Cells in a Streptozotocin-Induced Diabetic Rat Model.

STUDY DESIGN: Experimental study using a streptozotocin (STZ)-induced diabetic rat model. PURPOSE: This study aims to investigate whether insulin treatment could attenuate disc cell apoptosis and matrix degradation in a STZ-induced diabetic rat model. OVERVIEW OF LITERATURE: Diabetes is a significant risk factor for disc degeneration due to excessive apoptosis of disc cells and matrix degradation. However, no studies were noted to demonstrate the inhibitory effect of insulin treatment on the apoptosis of disc cells and matrix degradation in diabetic patients. METHODS: Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs). RESULTS: Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group. CONCLUSIONS: The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination.

Lipid droplets (LDs) are involved in various biological events in cells along with their primary role as a storage center for neutral lipids. Excessive accumulation of LDs is highly correlated with various diseases, including metabolic diseases. Therefore, a basic understanding of the molecular mechanism of LD degradation would be beneficial in both academic and industrial research. Lipophagy, a selective autophagy mechanism/LD degradation process, has gained increased attention in the research community. Herein, we sought to elucidate a novel lipophagy mechanism by utilizing the LD-degrading small molecule, SB2301, which activates ubiquitin-mediated lipophagy. Using a label-free target identification method, we revealed that ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) is a potential target protein of SB2301. We also demonstrated that although SB2301 does not modulate PCYT2 function, it induces the cellular translocation of PCYT2 to the LD surface and spatially increases the phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio of the LD membrane, causing LD coalescence, leading to the activation of lipophagy process to maintain energy homeostasis.

Physicochemical and Functional Properties of Yeast-Fermented Cabbage.

Microbial fermentation is often used to improve the functionality of plant-based food materials. Herein, we investigated changes in the physicochemical and functional properties of cabbage during yeast fermentation to develop new products using fermented cabbage. Among the 8 types of food-grade yeast, both Saccharomyces cerevisiae and Saccharomyces boulardii fermented 10% cabbage powder solution (w/w) the most effectively, leaving no soluble sugars after 12 h of fermentation. In addition, the yeast fermentation of cabbage resulted in functionally positive outcomes in terms of sulforaphane content, antioxidant properties, and anti-inflammatory activity. Specifically, the yeast-fermented cabbages contained about 500% more sulforaphane. The soluble fraction (5 µg/ml) of yeast-fermented cabbage had no cytotoxicity in murine RAW 264.7 cells, and the radical-scavenging capacity was equivalent to 1 µg/ml of ascorbic acid. Moreover, cabbage fermented with S. boulardii significantly suppressed both lipopolysaccharides (LPS)-induced nitric oxide production and LPS-induced reactive oxygen species production in RAW 264.7 cells, suggesting a potential anti-inflammatory effect. These results support the idea that yeast fermentation is promising for developing functionally improved cabbage products.

The genomic basis of temporal niche evolution in a diurnal rodent.

Patterns of diel activity-how animals allocate their activity throughout the 24-h daily cycle-play key roles in shaping the internal physiology of an animal and its relationship with the external environment.1,2,3,4,5 Although shifts in diel activity patterns have occurred numerous times over the course of vertebrate evolution,6 the genomic correlates of such transitions remain unknown. Here, we use the African striped mouse (Rhabdomys pumilio), a species that transitioned from the ancestrally nocturnal diel niche of its close relatives to a diurnal one,7,8,9,10,11 to define patterns of naturally occurring molecular variation in diel niche traits. First, to facilitate genomic analyses, we generate a chromosome-level genome assembly of the striped mouse. Next, using transcriptomics, we show that the switch to daytime activity in this species is associated with a realignment of daily rhythms in peripheral tissues with respect to the light:dark cycle and the central circadian clock. To uncover selection pressures associated with this temporal niche shift, we perform comparative genomic analyses with closely related rodent species and find evidence of relaxation of purifying selection on striped mouse genes in the rod phototransduction pathway. In agreement with this, electroretinogram measurements demonstrate that striped mice have functional differences in dim-light visual responses compared with nocturnal rodents. Taken together, our results show that striped mice have undergone a drastic change in circadian organization and provide evidence that the visual system has been a major target of selection as this species transitioned to a novel temporal niche.

AO Spine Adult Spinal Deformity Patient Profile: A Paradigm Shift in Comprehensive Patient Evaluation in Order to Optimize Treatment and Improve Patient Care.

STUDY DESIGN: Modified Delphi study. OBJECTIVE: Adult spinal deformity (ASD) is an increasingly recognized condition, comprising a spectrum of pathologies considerably impacting patients' health and functional status. Patients present with a combination of pain, disability, comorbidities and radiological deformity. The study aims to propose a systematic approach of gathering information on the factors that drive decision-making by developing a patient profile. METHODS: The present study comprises of 3 parts. Part 1: Development of prototype of patient profile: The data from the Core Outcome Study on SCOlisis (COSSCO) by Scoliosis Research Society (SRS) was categorized into a conceptual framework. Part 2: Modified Delphi study: Items reaching >70% agreement were included in a 4 round iterative process with 51 panellists across the globe. Part 3: Pilot testing-feasibility: Content validity and usability were evaluated quantitatively. RESULTS: The profile consisted of 4 domains. 1. General health with demographics and comorbidities, 2.Spine-specific health with spine related health and neurological status, 3. Imaging with radiographic and MRI parameters and 4. Deformity type. Each domain consisted of 1 or 2 components with various factors and their measuring instruments. Profile was found to have an excellent content validity (I-CVIr 0.78-1.00; Ave-CVI 0.92) appropriateness, relevance and usefulness. CONCLUSIONS: The present study, is first to provide a universally applicable multimodal ASD patient profile to methodically describe patients. Physicians are encouraged to assess ASD patients holistically using this profile and not just based on radiographic findings.

Postoperative changes of early-phase inflammatory indices after uncomplicated anterior cervical discectomy and fusion using allograft and demineralised bone matrix.

PURPOSES: We investigated sequential levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in uncomplicated ACDF (anterior cervical discectomy and fusion) using allograft and DBM (demineralised bone matrix) for primary cervical spondylosis and/or disc herniation. To our knowledge, there has been no study to investigate the diagnostic value of CRP and ESR for postoperative infection in ACDF using allograft and DBM. METHODS: Blood samples of 85 patients, who underwent one- (n = 51) or two-level (n = 34) ACDF, were obtained and evaluated before surgery and on the first, third, fifth, seventh, 14th, 30th, and 90th postoperative days. No infection was found in any patient for at least one year follow-up period. RESULTS: Mean CRP value increased significantly on the first postoperative day and reached a peak on the third postoperative day. The peak level rapidly decreased but remained elevated on the fifth, seventh, and 14th postoperative days. Mean ESR value increased significantly and reached a peak on the third postoperative day. The peak level gradually decreased but remained elevated on the fifth and seventh postoperative days. One- and two-level ACDF exhibited similar postoperative changes in CRP and ESR values and no significant difference in mean levels of CRP and ESR throughout the follow-up periods. CONCLUSIONS: This study demonstrates that uncomplicated ACDF using allograft and DBM showed significant abnormal values of CRP and ESR during the early postoperative period. This result suggests that abnormal values of CRP and ESR in the early postoperative period do not indicate acute postoperative infection after ACDF using allograft and DBM. Straying from the normal course, such as a second rise or a failure to decrease, of CRP and ESR is more important to signpost acute postoperative infection in ACDF using allograft and DBM.

Effect of nerve growth factor and its transforming tyrosine kinase protein and low-affinity nerve growth factor receptors on apoptosis of notochordal cells.

PURPOSE: The disappearance of notochordal cells by apoptosis is thought to be the starting point of intervertebral disc degeneration. The aim of this study was to determine the apoptotic pathway of notochordal cells as well as the anti-apoptotic potential of caspase inhibitors. METHODS: Rat notochordal cells were isolated, cultured, and placed in either 0 % (apoptosis-promoting condition) or 10 % (normal control) foetal bovine serum (FBS). We identified and quantified apoptotic cell deaths and caspase activities. In addition, we examined the cells for expression of nerve growth factor (NGF) and its two receptors--TrkA (survival signal) and p75 (apoptotic signal)--and downstream pathways. Finally, we analysed the degree of anti-apoptotic effects of caspase inhibitors on the cells. RESULTS: The apoptotic rate and expressions of caspase-8 (extrinsic pathway), -9 (intrinsic pathway), and -3 (common executioner) of notochordal cells were increased in 0 % FBS compared with those in 10 % FBS. Expressions of NGF, p75 receptor and JNK downstream pathways were also increased in 0 % FBS. In contrast, expressions of the TrkA receptor and Akt and MAPK downstream pathways were decreased in 0 % FBS. Pancaspase, capase-9 and capase-8 inhibitors significantly reduced apoptotic cell death. CONCLUSIONS: Our results suggest that notochordal cells undergo apoptosis through both the intrinsic and extrinsic pathways by activation of NGF, p75 receptor, and the JNK downstream pathway. We also found that apoptosis of notochordal cells can be attenuated by caspase inhibitors. Caspase inhibitors may play a therapeutic role in delaying the starting point of disc degeneration that is due to inappropriate or premature excessive apoptosis of notochordal cells.

An Overview of Antiviral Peptides and Rational Biodesign Considerations.

Viral diseases have contributed significantly to worldwide morbidity and mortality throughout history. Despite the existence of therapeutic treatments for many viral infections, antiviral resistance and the threat posed by novel viruses highlight the need for an increased number of effective therapeutics. In addition to small molecule drugs and biologics, antimicrobial peptides (AMPs) represent an emerging class of potential antiviral therapeutics. While AMPs have traditionally been regarded in the context of their antibacterial activities, many AMPs are now known to be antiviral. These antiviral peptides (AVPs) have been shown to target and perturb viral membrane envelopes and inhibit various stages of the viral life cycle, from preattachment inhibition through viral release from infected host cells. Rational design of AMPs has also proven effective in identifying highly active and specific peptides and can aid in the discovery of lead peptides with high therapeutic selectivity. In this review, we highlight AVPs with strong antiviral activity largely curated from a publicly available AMP database. We then compile the sequences present in our AVP database to generate structural predictions of generic AVP motifs. Finally, we cover the rational design approaches available for AVPs taking into account approaches currently used for the rational design of AMPs.

Lumbar Interbody Fusion and Osteobiologics for Lumbar Fusion.

Lumbar interbody fusion (LIF) is an excellent treatment option for a number of lumbar diseases. LIF can be performed through posterior, transforaminal, anterior, and lateral or oblique approaches. Each technique has its own pearls and pitfalls. Through LIF, segmental stabilization, neural decompression, and deformity correction can be achieved. Minimally invasive surgery has recently gained popularity and each LIF procedure can be performed using minimally invasive techniques to reduce surgery-related complications and improve early postoperative recovery. Despite advances in surgical technology, surgery-related complications after LIF, such as pseudoarthrosis, have not yet been overcome. Although autogenous iliac crest bone graft is the gold standard for spinal fusion, other bone substitutes are available to enhance fusion rate and reduce complications associated with bone harvest. This article reviews the surgical procedures and characteristics of each LIF and the osteobiologics utilized in LIF based on the available evidence.

Proximal Junctional Kyphosis in Adult Spinal Deformity: Definition, Classification, Risk Factors, and Prevention Strategies.

Proximal junctional problems are among the potential complications of surgery for adult spinal deformity (ASD) and are associated with higher morbidity and increased rates of revision surgery. The diverse manifestations of proximal junctional problems range from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). Although there is no universally accepted definition for PJK, the most common is a proximal junctional angle greater than 10° that is at least 10° greater than the preoperative measurement. PJF represents a progression from PJK and is characterized by pain, gait disturbances, and neurological deficits. The risk factors for PJK can be classified according to patient-related, radiological, and surgical factors. Based on an understanding of the modifiable factors that contribute to reducing the risk of PJK, prevention strategies are critical for patients with ASD.

Factors Affecting the Decision to Initiate Anticoagulation After Spine Surgery: Findings From the AOSpine Anticoagulation Global Initiative.

STUDY DESIGN: Cross-sectional, international survey. OBJECTIVES: To identify factors influencing pharmacologic anticoagulation initiation after spine surgery based on the AOSpine Anticoagulation Global Survey. METHODS: This survey was distributed to the international membership of AOSpine (n = 3805). A Likert-type scale described grade practice-specific factors on a scale from low (1) to high (5) importance, and patient-specific factors a scale from low (0) to high (3) importance. Analysis was performed to determine which factors were significant in the decision making surrounding the initiation of pharmacologic anticoagulation. RESULTS: A total of 316 spine surgeons from 64 countries completed the survey. In terms of practice-specific factors considered to initiate treatment, expert opinion was graded the highest (mean grade ± SD = 3.2 ± 1.3), followed by fellowship training (3.2 ± 1.3). Conversely, previous studies (2.7 ± 1.2) and unspecified guidelines were considered least important (2.6 ± 1.6). Patient body mass index (2.0 ± 1.0) and postoperative mobilization (2.3 ± 1.0) were deemed most important and graded highly overall. Those who rated estimated blood loss with greater importance in anticoagulation initiation decision making were more likely to administer thromboprophylaxis at later times (hazard ratio [HR] = 0.68-0.71), while those who rated drain output with greater importance were likely to administer thromboprophylaxis at earlier times (HR = 1.32-1.43). CONCLUSION: Among our global cohort of spine surgeons, certain patient factors (ie, patient mobilization and body mass index) and practice-specific factors (ie, expert opinion and fellowship training) were considered to be most important when considering anticoagulation start times.