Association of physical activity with fractures in kidney transplant recipients: A Korean nationwide cohort study.

Kidney transplant recipients are at high risk for fractures, primarily due to post-transplant bone disease. This retrospective cohort study analyzed data from the Korean National Health Insurance Service, including 10 083 kidney transplant recipients examined from 2009 to 2017. We assessed fracture incidence, emphasizing vertebral and hip fractures, and the association of physical activity and traditional risk factors with fracture risk. Kidney transplant recipients were categorized into three groups according to physical activity levels: non-activity, metabolic equivalent of task (MET) 1-499, and MET ≥500. Physical activity was associated with a decreased risk of all types of fractures: any (MET 1-499: adjusted hazard ratio (aHR) .75; 95% confidence interval (CI) .62-.92, MET ≥500: aHR .84; 95% CI .70-1.00), vertebral (MET 1-499: aHR .69; 95% CI .49-.98, MET ≥500: aHR .67; 95% CI .49-.91), and hip (MET 1-499: aHR .43; 95% CI .23-.81) fractures. Additionally, older age, female sex, and diabetes were associated with an increased fracture risk. The assessment of physical activity and traditional risk factors could improve fracture risk prediction. Our findings emphasize the need for further research to establish optimal physical activity recommendations for fracture prevention in kidney transplant recipients.

Role of quorum sensing and quorum quenching in anaerobic digestion: A scoping review.

Anaerobic digestion (AD) is a biological process that employs anaerobic microorganisms to degrade organic material, yielding biogas and biofertilizers. Understanding quorum sensing (QS) signaling in mixed microbial systems provides valuable insights into microbial behavior and functions. This review aims to examine recent studies on the roles of QS and QQ in the AD processes. A QS signal molecule, N-acyl homoserine lactone (AHL), induce the production of extraceluller polymers, promoting biofilm formation and bacterial aggregation, thereby the efficiency of AD process. QS-assisted granule formation fosters syntrophy between acetogens and methanogens, leading to increased organic removal and methane production. Specific AHLs were shown to be correlated with the abundance of hydrolytic bacteria and acidogens, further benefiting methane production. QQ was shown to effectively control membrane fouling in anaerobic membrane bioreactors, yet its impact on methane productivity remains unclear. This review shed lights on the existing literature gaps regarding the mechanisms of QS and QQ in AD systems, which will play a vital role in advancing AD applications in the future.

Complete Genome Sequence of Ralstonia solanacearum WR-1, a Virulent Strain on Solanum lycopersicum.

Ralstonia solanacearum is a bacterial wilt pathogen of Solanum lycopersicum. Its pathogenicity is the result of coevolution during continuous interaction with its host plants under given biotic and abiotic environments. To elucidate clues for pathogenicity of our WR-1 strain, its genome sequence was analyzed.

Complete Genome Sequence of Ralstonia pseudosolanacearum Strain Sw698, Isolated from Solanum lycopersicum.

Ralstonia pseudosolanacearum is a member of the Ralstonia solanacearum species complex (RSSC), which is composed of three species and diverse subspecific groups. Some strains cause bacterial wilt in Solanum lycopersicum; others are beneficial for their hosts. Herein, we present the complete genome sequence of an RSSC strain, Sw698, beneficial for S. lycopersicum growth.

Complete Genome Sequence of Ralstonia solanacearum Strain Bs715, a Member of Biovar 4 and a Strong Pathogen of Bacterial Wilt on Solanum lycopersicum.

Ralstonia solanacearum is a notorious pathogen of bacterial wilt on Solanum lycopersicum. Most isolates from diseased tomato tissues are biovar 3, and their genomes are publicly available; however, information on biovar 4 strains is limited. Here, the complete genome sequence of R. solanacearum Bs715, a biovar 4 strain, is presented.

Enhancement of biomethane recovery from batch anaerobic digestion by exogenously adding an N-acyl homoserine lactone cocktail.

Biomethane recovered through anaerobic digestion (AD) is a renewable, sustainable, and cost-effective alternative energy source that has the potential to help address rising energy demands. Efficient bioconversion during AD depends on the symbiotic relationship between hydrolytic bacteria and methanogenic archaea. Interactions between microorganisms occur in every biological system via a phenomenon known as quorum sensing (QS), in which signaling molecules are simultaneously transmitted and detected as a mode of cell-to-cell communication. However, there's still a lack of understanding on how QS works in the AD system, where diverse bacteria and archaea interact in a complex manner. In this study, different concentrations (0.5 and 5 µM) of signaling molecules in the form of an N-acyl homoserine lactone cocktail (C6-, C8-, C10-, and 3-oxo-C6-HSL) were prepared and introduced into anaerobic batch reactors to clearly assess how QS affects AD systems. It was observed that the methane yield increased with the addition of AHLs: a 5 µM AHL cocktail improved the methane yield (341.9 mL/g-COD) compared to the control without AHLs addition (285.9 mL/g-COD). Meanwhile, evidence of improved microbial growth and cell aggregation was noticed in AHLs-supplemented systems. Our findings also show that exogenously adding AHLs alters the microbial community structure by increasing the overall bacterial and archaeal population counts while favoring the growth of the methanogenic archaea group, which is essential in biomethane synthesis.

Maintenance of the critical care system during the pandemic in non-COVID-19 patients requiring continuous renal replacement therapy: a single center experience.

BACKGROUND: During the COVID-19 pandemic, maintenance of essential healthcare systems became very challenging. We describe the triage system of our institute, and assess the quality of care provided to critically ill non-COVID-19 patients requiring continuous renal replacement therapy (CRRT) during the pandemic. METHODS: We introduced an emergency triage pathway early in the pandemic. We retrospectively reviewed the medical records of patients who received CRRT in our hospital from January 2016 to March 2021. We excluded end-stage kidney disease patients on maintenance dialysis. Patients were stratified as medical and surgical patients. The time from hospital arrival to intensive care unit (ICU) admission, the time from hospital arrival to intervention/operation, and the in-hospital mortality rate were compared before (January 2016 to December 2019) and during (January 2021 to March 2021) the pandemic. RESULTS: The mean number of critically ill patients who received CRRT annually in the surgical department significantly decreased during the pandemic in (2016-2019: 76.5 ± 3.1; 2020: 56; p < 0.010). Age, sex, and the severity of disease at admission did not change, whereas the proportions of medical patients with diabetes (before: 44.4%; after: 56.5; p < 0.005) and cancer (before: 19.4%; after: 32.3%; p < 0.001) increased during the pandemic. The time from hospital arrival to ICU admission and the time from hospital arrival to intervention/operation did not change. During the pandemic, 59.6% of surgical patients received interventions/operations within 6 hours of hospital arrival. In Cox's proportional hazard modeling, the hazard ratio associated with the pandemic was 1.002 (0.778-1.292) for medical patients and 1.178 (0.783-1.772) for surgical patients. CONCLUSION: Our triage system maintained the care required by critically ill non-COVID-19 patients undergoing CRRT at our institution.

Efficacy of a Tibia Counter Rotator System for the Treatment of Internal Tibial Torsion in Children.

Internal tibial torsion is more common in the Asian population than in Western populations. Generally, surgery should be considered for the treatment of severe internal tibial torsion. As an alternative approach, the usefulness of a tibia counter rotator (TCR), a corrective orthosis based on the theory of the tibia torsional transformer, has been demonstrated, but the evidence is limited. In the present study, the efficacy and safety of TCR treatment were investigated in pediatric patients with internal tibial torsion. The subjects were 124 pediatric patients with internal tibial torsion who were between 3 and 15 years of age and had no underlying diseases. The severity of tibial intorsion was evaluated by the tibial transmalleolar angle (TMA). A TMA less than 5° was defined as internal tibial torsion, and less than −20° was defined as severe in this study. The median duration of TCR use was 11 (9, 12) (median (IQR: interquartile range)) months, and the treatment completion rate was 94.4% (117/124). The TMA at 12 months from the start of treatment in patients who completed treatment was 5° (0°, 10°) on the right (n = 66) (p < 0.01 vs. pretreatment) and 0° (−5°, 8°) on the left (n = 71) (p < 0.01 vs. pretreatment). The tibial torsional transformer used in this study is effective in the initial treatment of mild to severe internal tibial torsion, with no adverse effects. Although internal tibial torsion is generally expected to resolve spontaneously, TCR treatment may be an effective alternative to surgical therapy in the Asian pediatric population.

Worsening or improving hypoalbuminemia during continuous renal replacement therapy is predictive of patient outcome: a single-center retrospective study.

BACKGROUND: Hypoalbuminemia at the initiation of continuous renal replacement therapy (CRRT) is a risk factor for poor patient outcomes. However, it is unknown whether the patterns of changes in serum albumin levels during CRRT can be used to predict patient outcomes. METHODS: This retrospective study analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital. We included patients with acute kidney injury who received CRRT for ≥ 72 h. We divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.0 g/dL) at the initiation and termination of CRRT. RESULTS: The 793 patients in this study were categorized into the following albumin groups: persistently low, 299 patients (37.7%); increasing, 85 patients (10.4%); decreasing, 195 patients (24.6%); and persistently high, 214 patients (27.1%). In-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups. The hazard ratio for in-hospital mortality was 0.481 (0.340-0.680) in the increasing group compared to the persistently low group; it was 1.911 (1.394-2.620) in the decreasing group compared to the persistently high group. The length of ICU stay was 3.55 days longer in the persistently low group than in the persistently high group. CONCLUSIONS: Serum albumin levels changed during CRRT, and monitoring of patterns of change in serum albumin levels is useful for predicting in-hospital mortality and the length of ICU stay.

Immunoglobulin A nephropathy in a patient with neurofibromatosis type 1: A case report and literature review.

RATIONALE: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). PATIENT CONCERNS: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. DIAGNOSIS: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. INTERVENTION: The patient was advised to take 4 mg of perindopril. OUTCOME: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). LESSONS: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.

Pembrolizumab-induced focal segmental glomerulosclerosis: A case report.

RATIONALE: Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder that leads to end-stage kidney disease. Pembrolizumab, an immune checkpoint inhibitor, is an anti-programmed death 1 (PD-1) immunoglobulin G4 antibody approved for the treatment of advanced melanoma and can cause various renal immune-related adverse events (AEs), including acute kidney injury. Several cases of anti PD-1 therapy-induced glomerulonephritis have been reported so far, but FSGS has seldom been reported. PATIENT CONCERNS: 46-year old woman presented to our hospital with generalized edema. DIAGNOSES: Laboratory examination revealed features of nephrotic syndrome, and kidney biopsy confirmed FSGS. After other etiological factors of secondary FSGS were ruled out, she was diagnosed with FSGS caused by pembrolizumab. INTERVENTIONS: She did not resume treatment with pembrolizumab and was treated with irbesartan and furosemide according to the American Society of Clinical Oncology Practice guidelines. OUTCOMES: After 2 months, the features of nephrotic syndrome resolved. LESSONS: This case provides valuable insight into the etiology of FSGS that can occur as a renal immune-related AE of PD-1 inhibitor therapy. Therefore, patients should undergo evaluation for renal function and urinalysis at baseline and after treatment. If patients treated with PD-1 inhibitors present with renal injury and/or unexplained proteinuria >1 g/day, we would recommend a kidney biopsy to determine the underlying cause and establish an appropriate therapeutic plan.

Characterization of the structural determinants of the ubiquitin-dependent proteasomal degradation of human hepatic tryptophan 2,3-dioxygenase.

Human hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ∼2.3 h, relative to an average t1/2 of ∼2-3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation pathway. Additionally, we identified 15 ubiquitination K-sites and demonstrated that Trp-binding to an exosite impeded its proteolytic degradation. Here, we further established autophagic-lysosomal degradation as an alternative back-up pathway for cellular hTDO degradation. In addition, with protein kinases A and C, we identified 13 phosphorylated Ser/Thr (pS/pT) sites. Mapping these pS/pT sites on the hTDO surface revealed their propinquity to acidic Asp/Glu (D/E) residues engendering negatively charged DEpSpT clusters vicinal to the ubiquitination K-sites over the entire protein surface. Through site-directed mutagenesis of positively charged patches of gp78, previously documented to interact with the DEpSpT clusters in other target proteins, we uncovered the likely role of the DEpSpT clusters in the molecular recognition of hTDO by gp78 and plausibly other E3 Ub-ligases. Furthermore, cycloheximide-chase analyses revealed the critical structural relevance of the disordered N- and C-termini not only in the Ub-ligase recognition, but also in the proteasome engagement. Together, the surface DEpSpT clusters and the N- and C-termini constitute an intrinsic bipartite degron for hTDO physiological turnover.

Effect of Timing of Intravenous Fentanyl Administration on the Incidence of Posttonsillectomy Nausea and Vomiting.

OBJECTIVE/HYPOTHESIS: Fentanyl is commonly administered toward the end of tonsillectomy to prevent emergence delirium and reduce postoperative pain. However, it can delay emergence from anesthesia and increase the risk of postoperative nausea and vomiting (PONV). The goal of our study was to compare the risk of PONV based on the timing of fentanyl administration at the end of tonsillectomy in children. STUDY DESIGN: Prospective, double-blind, randomized controlled trial. METHODS: One hundred forty patients aged 3 to 7 years undergoing tonsillectomy were divided into two groups. Fentanyl (1 µg/kg) was administered at the end of surgery in group 1 (n = 70) and at 10 to 15 minutes before the end of surgery in group 2 (n = 70). Time to regular breathing and time to emergence from anesthesia were measured from the end of surgery. PONV and pediatric anesthesia emergence delirium scale scores were assessed every 10 minutes after admission to the postanesthesia care unit. RESULTS: Incidences of PONV (2.9% vs. 2.9%, P > .99) and emergence delirium (11.4% vs. 5.7%, P = .23) were not significantly different between the two groups. Time to regular breathing (mean difference = 2.3 minutes; 95% confidence interval [CI]: 0.9 to 3.7 minutes) and time to emergence (median difference = 6.5 minutes; 95% CI, 2.5 to 10.5 minutes) were significantly longer in group 1 than in group 2. CONCLUSIONS: Although there was no beneficial effect on PONV, recovery of regular breathing and consciousness was quicker with earlier fentanyl administration. Emergence delirium was well-controlled, similar to that with fentanyl administration at the end of surgery. LEVEL OF EVIDENCE: 1b Laryngoscope, 2020.

Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of in vitro as well as in vivo experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions.

Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance.

The hepatic endoplasmic reticulum (ER)-anchored monotopic proteins, cytochromes P450 (P450s), are enzymes that metabolize endobiotics (physiologically active steroids and fatty acids), as well as xenobiotics including therapeutic/chemotherapeutic drugs, nutrients, carcinogens, and toxins. Alterations of hepatic P450 content through synthesis, inactivation, or proteolytic turnover influence their metabolic function. P450 proteolytic turnover occurs via ER-associated degradation (ERAD) involving ubiquitin (Ub)-dependent proteasomal degradation (UPD) as a major pathway. UPD critically involves P450 protein ubiquitination by E2/E3 Ub-ligase complexes. We have previously identified the ER-polytopic gp78/AMFR (autocrine motility factor receptor) as a relevant E3 in CYP3A4, CYP3A23, and CYP2E1 UPD. We now document that liver-conditional genetic ablation of gp78/AMFR in male mice disrupts P450 ERAD, resulting in statistically significant stabilization of Cyp2a5 and Cyp2c, in addition to that of Cyp3a and Cyp2e1. More importantly, we establish that such stabilization is of the functionally active P450 proteins, leading to corresponding statistically significant enhancement of their drug-metabolizing capacities. Our findings, with clinically relevant therapeutic drugs (nicotine, coumarin, chlorzoxazone, and acetaminophen) and the prodrug (tamoxifen) as P450 substrates, reveal that P450 ERAD disruption could influence therapeutic drug response and/or toxicity, warranting serious consideration as a potential source of clinically relevant drug-drug interactions (DDIs). Because gp78/AMFR is not only an E3 Ub-ligase, but also a cell-surface prometastatic oncogene that is upregulated in various malignant cancers, our finding that hepatic gp78/AMFR knockout can enhance P450-dependent bioactivation of relevant cancer chemotherapeutic prodrugs is of therapeutic relevance and noteworthy in prospective drug design and development. SIGNIFICANCE STATEMENT: The cell-surface and ER transmembrane protein gp78/AMFR, a receptor for the prometastatic autocrine motility factor (AMF), as well as an E3 ubiquitin-ligase involved in the ER-associated degradation (ERAD) of not only the tumor metastatic suppressor KAI1 but also of hepatic cytochromes P450, is upregulated in various human cancers, enhancing their invasiveness, metastatic potential, and poor prognosis. Liver-specific gp78/AMFR genetic ablation results in functional protein stabilization of several hepatic P450s and consequently enhanced drug and prodrug metabolism, a feature that could be therapeutically exploited in the bioactivation of chemotherapeutic prodrugs through design and development of novel short-term gp78/AMFR chemical inhibitors.

Comparison of Cervical Sagittal Alignment and Kinematics after Posterior Full-endoscopic Cervical Foraminotomy and Discectomy According to Preoperative Cervical Alignment.

BACKGROUND: The progression of cervical kyphosis due to injury to the facet joints and musculature is a major concern for posterior foraminotomy especially for patients with cervical lordosis of less than 10°. However, cervical hypo-lordosis (cervical lordosis < 10°) may be improved with the alleviation of pain and muscle spasms, which corresponds with the disappearance of a positive Spurling's test. When surgery is necessary, the spontaneous recovery of cervical curvature may be minimally offset using minimally invasive surgical techniques, such as posterior percutaneous endoscopic cervical foraminotomy (P-PECF). OBJECTIVES: The primary objective was to compare the changes in cervical kinematics between patients with cervical lordosis (≥ 10°, group I) and hypo-lordosis (< 10°, group II) after P-PECF. STUDY DESIGN: This study was a retrospective nested case-control study with the IRB No. H-1210-078-434. SETTING: University Medical Center, Seoul, Korea. METHODS: P-PECFs were performed for patients with a radiculopathy due to single-level unilateral cervical foraminal soft-disc herniations or foraminal stenosis with minimal degeneration of the disc/facet joints and a positive Spurling's test. A retrospective nested case-control study was performed for 23 patients with cervical lordosis of ≥ 10° (group I; M:F = 15:8; age, 52.3 ± 9.8 years) and 23 patients with cervical lordosis of < 10°(group II; M:F = 15:8; age, 46.3 ± 12.7 years). P-PECFs were performed using the methods previously reported, and all patients were discharged the next day without limitations on neck motion. The patients were followed at one, 3, 6, and 12 months postoperatively and yearly thereafter. The follow-up period was 25.8 ± 19.6 months. Clinical outcomes were assessed using the visual analogue pain score of arms. The cervical angles (C2-7, tangential method) were measured on neutral (CA), flexion (CAF), and extension (CAE) lateral radiographs, and range of motion (C-ROM) was calculated by conducting a radiological analysis. A linear mixed model was used to assess the linearity of the changes in cervical curvatures during the postoperative 12 months between the groups. RESULTS: Significant reductions in arm pain and negative results on Spurling's test were initially achieved in 21/23 patients in group I and in 23/23 patients in group II with means of 1.7 ± 0.31 months and 1.09 ± 0.09 months, respectively. Using the mixed effect models, the interactions between group and time were significant for the CA (P = 0.004), CAE (P < 0.001), and C-ROM (P < 0.001) but not the CAF (P = 0.392). The CA (adjusted-P < 0.001), CAE (adjusted-P < 0.001), and C-ROM (adjusted-P = 0.046) exhibited significant between-group differences at the pre-operation. However, during the follow-up, these parameters were significantly changed in group II, especially during the postoperative 3 months. The CA, CAE, and C-ROM changed by -11.73°, -19.87°, and 20.32°, respectively. Postoperatively, 17/23 patients in group II and 22/23 patients in group I exhibited cervical lordosis of ≥ 10°. LIMITATIONS: This study was retrospective in design, and the inherent selection bias and limited statistical power should be considered. CONCLUSIONS: Cervical hypo-lordosis less than 10° may not be a contra-indication for P-PECF when the change of cervical curvature is not a structural change. A larger study is necessary to identify prognostic factors. Key words: Alignment, cervical vertebrae, disc, percutaneous, endoscopes, biomechanical phenomena, surgery, lordosis, kyphosis.

Sagittal imbalance in patients with lumbar spinal stenosis and outcomes after simple decompression surgery.

BACKGROUND CONTEXT: Lumbar spinal stenosis (LSS) is the most common lumbar degenerative disease, and sagittal imbalance is uncommon. Forward-bending posture, which is primarily caused by buckling of the ligamentum flavum, may be improved via simple decompression surgery. PURPOSE: The objectives of this study were to identify the risk factors for sagittal imbalance and to describe the outcomes of simple decompression surgery. STUDY DESIGN: This is a retrospective nested case-control study PATIENT SAMPLE: This was a retrospective study that included 83 consecutive patients (M:F=46:37; mean age, 68.5±7.7 years) who underwent decompression surgery and a minimum of 12 months of follow-up. OUTCOME MEASURES: The primary end point was normalization of sagittal imbalance after decompression surgery. METHODS: Sagittal imbalance was defined as a C7 sagittal vertical axis (SVA) ≥40 mm on a 36-inch-long lateral whole spine radiograph. Logistic regression analysis was used to identify the risk factors for sagittal imbalance. Bilateral decompression was performed via a unilateral approach with a tubular retractor. The SVA was measured on serial radiographs performed 1, 3, 6, and 12 months postoperatively. The prognostic factors for sagittal balance recovery were determined based on various clinical and radiological parameters. RESULTS: Sagittal imbalance was observed in 54% (45/83) of patients, and its risk factors were old age and a large mismatch between pelvic incidence and lumbar lordosis. The 1-year normalization rate was 73% after decompression surgery, and the median time to normalization was 1 to 3 months. Patients who did not experience SVA normalization exhibited low thoracic kyphosis (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02-1.10) (p<.01) and spondylolisthesis (HR, 0.33; 95% CI, 0.17-0.61) before surgery. CONCLUSIONS: Sagittal imbalance was observed in more than 50% of LSS patients, but this imbalance was correctable via simple decompression surgery in 70% of patients.

The patient-reported outcome of chronic pain after the harvest of anterior iliac bone for anterior cervical arthrodesis.

BACKGROUND: Anterior cervical fusion (ACF) with autologous iliac bone graft is a traditional surgical method, but high rate of chronic pain (30%) at the anterior iliac crest presents a considerable hindrance to harvesting iliac bone. The memory of acute pain may become fainter as time progresses, and the incidence of chronic pain may not be as high as previously reported. The primary objective was to show the patient-reported outcome of chronic pain in the anterior iliac crest. METHODS: Telephone surveys were conducted for patients with single-level ACF (group-S; n=72; M:F=52:20; median age, 53years), multiple-level ACF (group-M; n=61; M:F=40:21; 56years) using autologous iliac bone, and single-level ACF with a stand-alone cage (group-C; n=53; M:F=38:15; 51years). Logistic regression analysis was performed to determine the risk factors, and the variables included group, age, gender, postoperative period and satisfaction with the surgical outcome. RESULTS: There was no chronic pain in 87% of the patients, with no difference among the groups (p=0.52). During the acute postoperative period, patients remembered no pain in 38/72 (53%) patients of group-S, 25/61 (41%) of group-M and 42/53 (79%) of group-C (p<0.001). Female gender (p=0.027; OR, 2.68; 95% CI, 1.12-6.41) was the risk factor for chronic pain. CONCLUSIONS: Iliac bone harvest may not cause chronic pain in 87% of patients, and the memory of acute pain was faded in 40-50% of patients. Female gender was a risk factor for chronic pain. This information should be considered before harvesting iliac bone.

Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase.

Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) play a central role in tryptophan metabolism and are involved in many cellular and disease processes. Here we report the crystal structure of human TDO (hTDO) in a ternary complex with the substrates L-Trp and O2 and in a binary complex with the product N-formylkynurenine (NFK), defining for the first time the binding modes of both substrates and the product of this enzyme. The structure indicates that the dioxygenation reaction is initiated by a direct attack of O2 on the C2 atom of the L-Trp indole ring. The structure also reveals an exo binding site for L-Trp, located ~42 Å from the active site and formed by residues conserved among tryptophan-auxotrophic TDOs. Biochemical and cellular studies indicate that Trp binding at this exo site does not affect enzyme catalysis but instead it retards the degradation of hTDO through the ubiquitin-dependent proteasomal pathway. This exo site may therefore provide a novel L-Trp-mediated regulation mechanism for cellular degradation of hTDO, which may have important implications in human diseases.

CHIP(-/-)-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications.

Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP(-/-)-mice over the first 8-9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5'-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP(-/-)-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models.