Truncated GPNMB, a microglial transmembrane protein, serves as a scavenger receptor for oligomeric ß-amyloid peptide1-42 in primary type 1 microglia.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is up-regulated in one subtype of microglia (MG) surrounding senile plaque depositions of amyloid-beta (Aß) peptides. However, whether the microglial GPNMB can recognize the fibrous Aß peptides as ligands remains unknown. In this study, we report that the truncated form of GPNMB, the antigen for 9F5, serves as a scavenger receptor for oligomeric Aß1-42 (o-Aß1-42 ) in rat primary type 1 MG. 125 I-labeled o-Aß1-42 exhibited specific and saturable endosomal/lysosomal degradation in primary-cultured type 1 MG from GPNMB-expressing wild-type mice, whereas the degradation activity was markedly reduced in cells from Gpnmb-knockout mice. The Gpnmb-siRNA significantly inhibits the degradation of 125 I-o-Aß1-42 by murine microglial MG5 cells. Therefore, GPNMB contributes to mouse MG's o-Aß1-42 clearance. In rat primary type 1 MG, the cell surface expression of truncated GPNMB was confirmed by a flow cytometric analysis using a previously established 9F5 antibody. 125 I-labeled o-Aß1-42 underwent endosomal/lysosomal degradation by rat primary type 1 MG in a dose-dependent fashion, while the 9F5 antibody inhibited the degradation. The binding of 125 I-o-Aß1-42 to the rat primary type 1 MG was inhibited by 42% by excess unlabeled o-Aß1-42 , and by 52% by the 9F5 antibody. Interestingly, the 125 I-o-Aß1-42 degradations by MG-like cells from human-induced pluripotent stem cells was inhibited by the 9F5 antibody, suggesting that truncated GPNMB also serve as a scavenger receptor for o-Aß1-42 in human MG. Our study demonstrates that the truncated GPNMB (the antigen for 9F5) binds to oligomeric form of Aß1-42 and functions as a scavenger receptor on MG, and 9F5 antibody can act as a blocking antibody for the truncated GPNMB.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

MRI characteristics of disc degeneration after condoliase injection in young patients: A consecutive case series.

BACKGROUND: Lumbar disc herniation (LDH) results in low back pain due to nerve root compression caused by nucleus pulposus degeneration. Chemonucleolysis of the nucleus pulposus by injection of condoliase is less invasive than surgery, but may cause disc degeneration. The purpose of the study was to examine outcomes of condoliase injection in patients in their teens and twenties using Pfirrmann criteria on MRI. METHODS: A single-center retrospective study was performed in 26 consecutive patients (19 men, 7 women) who underwent condoliase injection (1 mL, 1.25 U/mL) for LDH and had MRI scans at 3 and 6 months. Cases with and without an increase in Pfirrmann grade at 3 months post-injection were included in groups D (disc degeneration, n = 16) and N (no degeneration, n = 10). Pain was measured on a visual analogue scale (VAS). MRI findings were evaluated using the % change in disc height index (ΔDHI). RESULTS: The mean age of the patients was 21.1 ± 4.1 years and 12 were <20 years old. At baseline, 4, 21 and 1 were in Pfirrmann grades II, III and IV. In group D, no case had a further increase in Pfirrmann grade from 3 to 6 months. Pain significantly decreased in both groups. There were no adverse events. MRI showed a significant decrease in ΔDHI from 100% pre-injection to 89.4 ± 9.7% at 3 months in all cases (p < 0.05). There was a significant recovery in ΔDHI in group D from 3 to 6 months (85.4 ± 9.3% vs. 86.7 ± 9.1%, p < 0.05). CONCLUSIONS: These results suggest that chemonucleolysis with condoliase is effective and safe for LDH in young patients. Progression of Pfirrmann criteria at 3 months post-injection occurred in 61.5% of cases, but disc degeneration showed recovery in these patients. A longer-term study of the clinical symptoms related to these changes is required.

Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.

To maintain the oxygen supply, the production of red blood cells (erythrocytes) is promoted under low-oxygen conditions (hypoxia). Oxygen is carried by hemoglobin in erythrocytes, in which the majority of the essential element iron in the body is contained. Because iron metabolism is strictly controlled in a semi-closed recycling system to protect cells from oxidative stress caused by iron, hypoxia-inducible erythropoiesis is closely coordinated by regulatory systems that mobilize stored iron for hemoglobin synthesis. The erythroid growth factor erythropoietin (EPO) is mainly secreted by interstitial fibroblasts in the renal cortex, which are known as renal EPO-producing (REP) cells, and promotes erythropoiesis and iron mobilization. Intriguingly, EPO production is strongly induced by hypoxia through iron-dependent pathways in REP cells. Here, we summarize recent studies on the network mechanisms linking hypoxia-inducible EPO production, erythropoiesis and iron metabolism. Additionally, we introduce disease mechanisms related to disorders in the network mediated by REP cell functions. Furthermore, we propose future studies regarding the application of renal cells derived from the urine of kidney disease patients to investigate the molecular pathology of chronic kidney disease and develop precise and personalized medicine for kidney disease.

Structural model for ligand binding and channel opening of an insect gustatory receptor.

Insect gustatory receptors play roles in sensing tastants, such as sugars and bitter substances. We previously demonstrated that the BmGr9 silkworm gustatory receptor is a d-fructose-gated ion channel receptor. However, the molecular mechanism of how d-fructose could initiate channel opening were unclear. Herein, we present a structural model for a channel pore and a d-fructose-binding site in BmGr9. Since the membrane topology and oligomeric state of BmGr9 appeared to be similar to those of an insect odorant receptor coreceptor, Orco, we constructed a structural model of BmGr9 based on the cryo-EM Orco structure. Our site-directed mutagenesis data suggested that the transmembrane region 7 forms channel pore and controls channel gating. This model also suggested that a pocket formed by transmembrane helices 2 to 4 and 6 binds d-fructose. Using mutagenesis experiments in combination with docking simulations, we were able to determine the potent binding mode of d-fructose. Finally, based on these data, we propose a conformational change that leads to channel opening upon d-fructose binding. Taken together, these findings detail the molecular mechanism by which an insect gustatory receptor can be activated by its ligand molecule.

Association between misoprostol and nonsteroidal anti-inflammatory drug-induced kidney injury: A systematic review and meta-analysis.

AIMS: Misoprostol is a prostaglandin E1 analogue that is used to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal disorders. The aim of this systematic review and meta-analysis was to evaluate whether use of misoprostol also decreases the risk of NSAID-induced kidney injury. METHODS: Randomized controlled trials that compared misoprostol vs. placebo in an adult patient population were selected. The primary outcome was kidney injury and the secondary outcome was severe adverse events. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twelve studies were eligible for inclusion. Although the rates of kidney injury and severe adverse events did not differ significantly between misoprostol and placebo, a posthoc subgroup analysis that excluded studies in which different NSAIDs were used in the misoprostol and placebo groups suggested that misoprostol may reduce the risk of NSAID-induced kidney injury (risk difference -0.09, 95% confidence interval -0.15 to -0.03, P < .01, I2  = 87%; evidence of very low certainty). CONCLUSION: There is limited evidence that misoprostol reduces the risk of NSAID-induced kidney injury. Misoprostol possibly contributes to reducing the risk of kidney injury associated with chronic NSAID use. The findings of this meta-analysis suggest further high-quality clinical trials are warranted.

Factors associated with disc degeneration based on Pfirrmann criteria after condoliase treatment for lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) is a common cause of low back pain and is associated with degeneration of the nucleus pulposus causing nerve root compression. Chemonucleolysis of the nucleus pulposus with condoliase is a low-invasive treatment for LDH. The purpose of this study was to investigate changes in Pfirrmann criteria, which are used to evaluate disc degeneration, after injection of condoliase into a herniated intervertebral disc, and to identify factors associated with disc degeneration at 3 months post-injection. METHODS: Medical records and radiographic findings were reviewed retrospectively for 127 patients with LDH (88 male, 39 female, mean age: 46.6 ± 17.1 years, mean follow-up: 9.8 ± 7.8 months) who underwent chemonucleolysis with intradiscal condoliase injection at our center since September 2018. Condoliase (1.25 U/mL; 1 mL volume) was injected toward the middle of the affected intervertebral nucleus pulposus using a 21-gauge disc-puncture needle. RESULTS: Cases in which the Pfirrmann grade did and did not progress in the 3 months after the injection were included in groups P (progression, n = 49) and NP (non-progression, n = 78), respectively. Logistic regression analysis of progression of Pfirrmann grade post-injection showed significant associations with age <40 years (p = 0.013, odds ratio (OR): 3.69, 95% confidence interval (CI): 1.32-10.31), Pfirrmann Grade II or III at baseline (p = 0.021, OR: 3.51, 95% CI: 1.24-9.64), and a high-intensity MRI signal in the herniation (p = 0.047, OR: 2.97, 95% CI: 1.03-8.87). Patients in group P had significantly higher rates of disc height decrease ≥20%, reduced herniated disc size, and improved VAS for pain, but both groups had significant decreases in pain. No cases had anaphylactic shock or neurologic sequelae. CONCLUSIONS: These results show the safety and efficacy of chemonucleolysis with condoliase for treatment of painful LDH. Progression of Pfirrmann criteria on MRI at 3 months after injection was significantly associated with an improved clinical outcome.

Laterality of lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) is most common in men aged 20-40 at the L4/5 level; however, left-right differences have not been reported. Improving our understanding of left- and right-side LDH may facilitate the estimation of mechanical load on intervertebral discs. Here, we assessed left-right differences in LDH via a retrospective analysis of LDH cases. METHODS: Among 10,972 surgical cases of LDH identified in the Nagoya Spine Group database, 2899 in which right- and left-LDH sides were observable in a single vertebral segment were identified (mean age 46.3 ± 16.6 years, 2028 males). The following characteristics of patients with right- and left-LDH were compared: age, LDH level, surgical technique, operative time, blood loss, length of hospital stay, preoperative Japan Orthopaedic Association (JOA) score, and JOA recovery rate. RESULTS: LDH occurred on the right and left sides in 1358 and 1541 patients, respectively, with patients with right-side LDH significantly older than those with left (47.9 ± 16.6 versus 45.0 ± 16.5, respectively; p < 0.001). No between-group differences in sex, age, LDH level, surgical technique, operative time, blood loss, length of hospital stay, preoperative JOA score, or JOA recovery rate were observed. The occurrence of right-side LDH increased with age, occurring in 42.7%, 45.1%, 49.9%, and 54.7% of patients aged 10-29, 30-49, 50-69, and 70-89 years, respectively. CONCLUSION: Left-side LDH was observed more frequently than right; however, right-side LDH incidence increased with age. No significant between-group differences regarding symptoms, treatments, or outcomes were observed.

Validation of the obesity paradox by body mass index and waist circumference in patients undergoing percutaneous coronary intervention.

BACKGROUND: The paradoxical association of obesity with mortality, named the "obesity paradox", has been inconsistent, possibly due to a difference between body mass index (BMI) and central obesity, estimated by waist circumference (WC) as patterns of adiposity. SUBJECTS/METHODS: We enrolled 8513 participants from the Kumamoto Intervention Conference Study, a multicenter registry that included consecutive patients undergoing percutaneous coronary intervention (PCI) at 18 centers between 2008 and 2017 in Japan. Patients were divided into quartiles in ascending order of the BMI or WC. The primary endpoints were all-cause mortality and cardiovascular death within a year. RESULTS: There were 186 deaths (case fatality rate, 22.1/1000 person-years) during the follow-up period. The lowest group (1st quartile) of BMI or WC had the worst prognosis among the quartiles (1st quartile, 4.2%; 2nd quartile, 1.9%; 3rd quartile, 1.5%; 4th quartile, 1.1%; P < 0.001 (χ2) and 1st quartile, 4.1%; 2nd quartile, 2.3%; 3rd quartile, 1.2%; 4th quartile, 1.5%; P < 0.001 (χ2), respectively). Similar results were obtained for cardiovascular death. In a multivariable analysis adjusted by nine conventional factors, the lowest group (1st quartile) of BMI (hazards ratio, 2.748; 95% confidence interval [CI], 1.712-4.411) and WC (hazards ratio, 2.340; 95% CI, 1.525-3.589) were independent prognostic factors for all-cause mortality. By dividing the participants into two groups according to either the BMI or WC based on the National Cholesterol Education Program Adult Treatment Panel III and World Health Organization classification, the highest mortality was observed in the lower group. However, the C-statistic after adding BMI (quartile) to conventional factors was found to be slightly higher than BMI (two categories) and WC (two categories) (0.735 vs. 0.734). CONCLUSIONS: The obesity paradox was observed in patients after PCI, and single-use of BMI (or WC) was sufficient to predict the prognosis of patients after PCI.

Risk factors for subchondral insufficiency fracture of the femoral head in renal transplant patients.

INTRODUCTION: Risk factors associated with subchondral insufficiency fracture (SIF) of the femoral head have not been established. The aim of the present study was to determine the incidence and risk factors for SIF of the femoral head following renal transplantation (RT). MATERIALS AND METHODS: We analyzed the cases of 681 RT patients (mean age at surgery: 49.5 ± 13.6 years, 249 women, 432 men) to determine the incidence of SIF. Hip magnetic resonance imaging (MRI) was performed 6 months post-RT. The following potential predictors of SIF were evaluated: (1) patient's condition at RT: bone mineral density (BMD), pre-RT laboratory values including calcium (Ca), phosphorus (P), calcium-phosphorus product (Ca × P), and intact parathyroid hormone; the patient and donor's blood relationship; and mismatching number of human leukocyte antigens (HLAs), and (2) post-RT dosage(s) of steroid(s), the immunosuppressive regimen, and the incidence of acute rejection. RESULTS: SIF was observed in 15 hips (13 patients, 1.9%). We successfully matched 39 patients without SIF. A multivariate logistic regression analysis adjusted for cumulative dosages of steroids, revealed the following were risk factors for SIF: osteoporosis (OR: 11.4, p = 0.046), lumbar BMD (OR: 0.003, p = 0.038), pre-RT serum P (OR 2.68, p = 0.004), and pre-RT serum Ca × P (OR: 1.11, p = 0.005). CONCLUSION: Since osteoporosis, the lumbar BMD, serum P, and serum Ca × P were identified as risk factors for a post-RT SIF, these factors should be evaluated before RT for the prediction of the SIF risk.

Emotional valence of self-defining memories in older adults: A longitudinal study.

The present study aimed to evaluate the pleasantness bias and fading affect bias in self-defining memories (SDMs) and to examine the relationship between their emotional valence of SDMs and cognitive function and serotonin transporter polymorphisms (5-HTTLPR) with a prospective longitudinal method. Ninety-two older adults recalled SDMs twice at an interval of one year (T1 and T2). The results showed a pleasantness bias and a fading affect bias in SDMs. The higher the working memory was, the higher the vividness of SDMs and the higher the concordance rate of SDMs between T1 and T2. Meanwhile, cognitive performance had no effect on the emotional valence of SDMs. Additionally, the repeatedly recalled SDMs in the S/S allele carriers of the 5-HTTLPR polymorphism changed with a lower negative valence at T2 than at T1. The 5-HTTLPR polymorphism may be a plasticity factor that predicts positive outcomes in positive situations.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

Prognostic factors for acute ischemic stroke in patients undergoing hemodialysis.

BACKGROUND: Acute ischemic stroke (AIS) is a critical complication in patients undergoing dialysis. Although the improvement of AIS management is an urgent requirement, few studies have evaluated the prognostic factors of AIS in these patients. This study aimed to assess the relationship between clinical factors in patients undergoing dialysis and the prognosis of AIS. METHODS: Among 1267 patients who were hospitalized for AIS in Sendai City Hospital from January 2015 to June 2020, 81 patients undergoing hemodialysis were retrospectively enrolled. Multivariate analysis was performed to evaluate the effect of baseline characteristics, dialysis factors, and neurological severity of patients at admission [National Institutes of Health Stroke Scale (NIHSS) score] on in-hospital mortality, physical disability, and the need for rehabilitation transfer. RESULTS: A higher NIHSS score was a critical risk factor for each outcome and the only significant factor for in-hospital mortality [odds ratio (OR)/point 1.156, 95% confidence interval (CI) 1.054-1.267]. The risk factors of physical disability were NIHSS score (OR/point 1.458, 95% CI 1.064-1.998), older age (OR/year 1.141, 95% CI 1.022-1.274), diabetic nephropathy (OR 7.096, 95% CI 1.066-47.218), and higher premorbid modified Rankin scale (mRS) score (OR/grade 2.144, 95% CI 1.155-3.978); while those of rehabilitation transfer were a higher NIHSS score (OR/point 1.253, 95% CI 1.080-1.455), dialysis vintage (OR/year 1.175, 95% CI 1.024-1.349), and intradialytic hypotension before onset (OR 5.430, 95% CI 1.320-22.338). CONCLUSIONS: Along with neurological severity, dialysis vintage, intradialytic hypotension, and diabetic nephropathy could worsen the prognosis of patients with AIS undergoing hemodialysis.

The effect of Dioscorea esculenta powder on prostaglandin E2 and cytochrome c oxidase subunit 2 levels, menstrual pain, and premenstrual syndrome in young women: A randomized double-blind controlled trial.

Background Diosgenin, extracted from Dioscorea esculenta, has been reported to decrease prostaglandin E2 (PGE2) levels and any other inflammatory cytokine in rodents. However, it is still unclear whether D. esculenta intake suppressed PGE2 production and menstrual pain and premenstrual syndrome (PMS) in younger female. Aim This study aims to investigate the effect of D. esculenta intake on PGE2 and cytochrome c oxidase subunit 2 (COX-2) levels and on menstrual pain and PMS in young women. This is a randomized, double-blind, placebo-controlled, crossover study. Methods Ten healthy young females were administered either a placebo or D. esculenta (300 mg/day) for 4 weeks, followed by a 4-week washout period. Fasting blood sample was taken from the fingertips on the second day of menstrual cycle began and obtained 24h before the last D. esculenta to avoid acute effects. Participants then switched treatments for 4 weeks as a second trial. Plasma PGE2 and COX-2 levels were measured before and after each trial. The visual analogue scale (VAS), McGill pain questionnaire (MPQ), and Daily Record of Severity of Problems (DRSP) were also evaluated. The study was set and conducted from 2019 to 2020. Results PGE2 and COX-2 levels significantly decreased after D. esculenta intake compared to placebo (p = 0.038, p = 0.042 each). The VAS and DRSP scores were also significantly lower after D. esculenta intake (p = 0.046, p = 0.035 each). Conclusion Four-week D. esculenta intake suppressed PGE2 and COX-2 levels resulting in an improvement in PMS symptoms and menstrual pain in young women.

Recurrent Syncope in a Case with Mediastinal Lymphoma.

An 83-year-old man suddenly lost consciousness, and his blood pressure dropped. Results of blood analysis were within normal range. A chest radiograph showed enlargement of the left mediastinum. Computed tomographic scan of the chest showed a large mass surrounding the left common carotid artery in the left upper mediastinum. Histology revealed a large B-cell lymphoma. A Holter ECG showed transient sinus bradycardia and atrioventricular block. The power spectrum revealed increase in power of high frequency, suggesting that general vagal activity might be related to bradycardia. Evaluation of autonomic system from high frequency and low frequency components may be useful in examining the mechanisms of sudden bradycardia and/or hypotension of unknown origin.

The History and Development of the Percutaneous Pedicle Screw (PPS) System.

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using the SEXTANT® system (Medtronic) featured the first generation of commercially available percutaneous pedicle screw (PPS) system in 2001. The innovative system has since become standard instrumentation used worldwide, and PPS is now used for long-segment minimally invasive surgery (MIS) spinal fixation from the thoracic spine to the pelvis for pathological conditions. PPS systems have been developed for approximately 20 years for the purpose of improving minimally invasive techniques, safety of instrumentation, and ease of use. The third-generation PPS systems established the insertion technique, and the development of the fourth-generation PPS systems have made great strides in minimizing the number of steps in the operative procedure. In the future, PPS systems are expected to continue making use of the latest technological advancements and to develop further with the aim of ensuring greater safety, reducing operator stress, and preventing complications such as insertion errors and infection. In this review article, we describe the historical evolution from the first-generation PPS system to the current PPS systems used today.

Efficacy of Minimally Invasive Trans-Sacral Canal Plasty between Patients with and without Failed Back Surgery Syndrome.

Background and Objectives: Clinicians are required to manage a growing number of elderly patients with several medical comorbidities, and invasive surgical treatments are sometimes not advisable for these patients. The aim of this study was to evaluate the efficacy of minimally invasive intraspinal canal treatment, trans-sacral canal plasty (TSCP), for patients with and without failed back surgery syndrome (FBSS). Materials and Methods: A multicenter analysis was conducted. TSCP was performed in patients with chronic low back pain and leg pain due to lumbar spinal disorders. An adhesiolysis by TSCP was carried out, then a mixture of steroid and local anesthesia was injected. Visual Analog Scales (VAS) for low back pain and leg pain, and complications were evaluated. Results: A total of 271 patients with a minimum 6-month follow-up were enrolled. There were 80 patients who had a history of previous lumbar spinal surgery (F group), and 191 patients without previous lumbar spinal surgery (N group). There were no significant differences in sex and age between the two groups. VAS scores for low back pain (N group/F group) preoperatively, immediately postoperatively, and 1 month, 3 months and 6 months postoperatively, were 51/52 mm, 24/26 mm, 33/34 mm, 30/36 mm, and 30/36 mm, respectively. VAS scores for leg pain were 69/67 mm, 28/27 mm, 39/41 mm, 36/43 mm, and 32/40 mm, respectively. Both VAS scores for low back pain and leg pain were significantly decreased from baseline to final follow-up in both groups (p < 0.01). However, VAS scores for leg pain at 3 months and 6 months postoperatively were significantly higher in F group (p < 0.05). There were three catheter breakages (2/3 in F group), and one dural tear in F group. Conclusions: TSCP significantly reduced both VAS scores for low back and leg pain in patients with and without FBSS. However, co-existence of intractable epidural adhesion might be associated with less improvement in FBSS.

Minimally Invasive Spinal Treatment (MIST)-A New Concept in the Treatment of Spinal Diseases: A Narrative Review.

In the past two decades, minimally invasive spine surgery (MISS) techniques have been developed for spinal surgery. Historically, minimizing invasiveness in decompression surgery was initially reported as a MISS technique. In recent years, MISS techniques have also been applied for spinal stabilization techniques, which were defined as minimally invasive spine stabilization (MISt), including percutaneous pedicle screws (PPS) fixation, lateral lumbar interbody fusion, balloon kyphoplasty, percutaneous vertebroplasty, cortical bone trajectory, and cervical total disc replacement. These MISS techniques typically provide many advantages such as preservation of paraspinal musculature, less blood loss, a shorter operative time, less postoperative pain, and a lower infection rate as well as being more cost-effective compared to traditional open techniques. However, even MISS techniques are associated with several limitations including technical difficulty, training opportunities, surgical cost, equipment cost, and radiation exposure. These downsides of surgical treatments make conservative treatments more feasible option. In the future, medicine must become "minimally invasive" in the broadest sense-for all patients, conventional surgeries, medical personnel, hospital management, nursing care, and the medical economy. As a new framework for the treatment of spinal diseases, the concept of minimally invasive spinal treatment (MIST) has been proposed.

Seasonal variation in incidence and causal organism of surgical site infection after PLIF/TLIF surgery: A multicenter study.

BACKGROUND: Postoperative SSI is a common and potentially serious complication in spine surgery. Seasonal variation occurs in rates of nosocomial infection, with higher rates found in the summer, during which hot, humid conditions may be optimal for proliferation of bacteria. This might also influence the rate of SSI. The purpose of the study was to examine seasonal variation in SSI after PLIF/TLIF surgery, including relationships with experience of surgeons and causal organisms. METHODS: Cases with SSI after PLIF/TLIF surgery at 10 facilities between January 1, 2012, and December 31, 2014 were retrieved from a database. Infection was defined based on CDC guidelines for SSIs. Patients were followed for at least two years after surgery. Surgeries were examined in spring (April-June), summer (July-September), autumn (October-December), and winter (January-March). Seasonal variation and other factors with a potential association with SSIs were evaluated. RESULTS: A total of 1174 patients (607 males, 567 females) who underwent PLIF/TLIF surgery were identified. The operations were PLIF (n = 667), TLIF (n = 443), MIS-PLIF (n = 27), and MIS-TLIF (n = 37). The total SSI rate for the 2-year period was 2.5% (29/1174), and the 2-year average SSI rates for surgeries in each season were spring, 2.6% (7/266); summer, 3.9% (13/335); fall, 1.3% (4/302); winter, 1.8% (5/271). The SSI rate was significantly higher in summer than non-summer (3.9% vs. 1.9%, p < 0.05). SSIs were caused by a variety of pathogens, including Gram-positive cocci, and Staphylococcus aureus was the most common pathogenic organism to cause SSI. CONCLUSION: Seasonality should be taken into account in strategies for SSI prevention, with particular attention on mitigation of increased temperature and humidity in the summer and on infection caused by Gram-positive cocci and S. aureus.

Dehydroepiandrosterone activates 5'-adenosine monophosphate-activated protein kinase and suppresses lipid accumulation and adipocyte differentiation in 3T3-L1 cells.

Substantial evidence has linked dehydroepiandrosterone (DHEA) levels to the anti-obesity and anti-diabetic effects of exercise. While 5'-adenosine monophosphate-activated protein kinase (AMPK) is a negative regulator of adipocyte differentiation and lipid accumulation, activation of mammalian target of rapamycin complex 1 (mTORC1), which is inhibited by AMPK, is required for adipocyte differentiation and positively regulates lipid accumulation. DHEA treatment activates the AMPK pathway in C2C12 myotubes. Hence, DHEA addition to preadipocytes and adipocytes might activate AMPK and inhibit mTORC1, resulting in the inhibition of adipogenesis and lipid accumulation. Therefore, we investigated the effect of DHEA on the AMPK pathway, mTORC1 activity, adipocyte differentiation, and lipid accumulation in 3T3-L1 cells. DHEA suppressed lipid accumulation and adipogenic marker expression during differentiation. It also activated AMPK signaling in preadipocytes and adipocytes and suppressed mTORC1 activity during differentiation. These results suggest that the activation of the AMPK pathway and inhibition of mTORC1 activity may mediate the anti-obesity effect of DHEA, providing novel molecular-level insights into its physiological functions.