Epiphytic Bacterial Community Analysis of Ulva prolifera in Garorim and Muan Bays, Republic of Korea.

The bacterial communities related to seaweed can vary considerably across different locations, and these variations influence the seaweed's nutrition, growth, and development. To study this further, we evaluated the bacteria found on the green marine seaweed Ulva prolifera from Garorim Bay and Muan Bay, two key locations on Republic of Korea's west coast. Our analysis found notable differences in the bacterial communities between the two locations. Garorim Bay hosted a more diverse bacterial population, with the highest number of ASVs (871) compared to Muan Bay's 156 ASVs. In Muan Bay, more than 50% of the bacterial community was dominated by Pseudomonadota. On the other hand, Garorim Bay had a more balanced distribution between Bacteroidota and Pseudomonadota (37% and 35.5%, respectively). Additionally, Cyanobacteria, particularly Cyanothece aeruginosa, were found in significant numbers in Garorim Bay, making up 8% of the community. Mineral analysis indicated that Garorim Bay had higher levels of S, Na, Mg, Ca, and Fe. Function-wise, both locations exhibited bacterial enrichment in amino acid production, nucleosides, and nucleotide pathways. In conclusion, this study broadens our understanding of the bacterial communities associated with Ulva prolifera in Korean waters and provides a foundation for future research on the relationships between U. prolifera and its bacteria.

Repeated Infusions of Bone-Marrow-Derived Mesenchymal Stem Cells over 8 Weeks for Steroid-Refractory Chronic Graft-versus-Host Disease: A Prospective, Phase I/II Clinical Study.

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.

Disaggregation-Activated pan-COX Imaging Agents for Human Soft tissue Sarcoma.

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD-IMC-1, BD-IMC-2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD-IMC-1 showcased higher susceptibility to disaggregation compared to BD-IMC-2, consistent with their selective interaction with COX. Notably, the BD-IMC-1 revealed positive cooperativity binding to COX-2 at sub-micromolar ranges. Both probes showed significant fluorescence turn-on upon LPS or PMA triggered COX-2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos-LM2) up to 2-fold increase with negligible toxicity. More importantly, the BD-IMC-1 demonstrated their practical imaging for COX-2 positive cells in paraffin-fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications.

Robotic-Assisted Spine Surgery: Role in Training the Next Generation of Spine Surgeons.

OBJECTIVE: This study aimed to assess the degree of interest in robot-assisted spine surgery (RASS) among residents and to investigate the learning curve for beginners performing robotic surgery. METHODS: We conducted a survey to assess awareness and interest in RASS among young neurosurgery residents. Subsequently, we offered a hands-on training program using a dummy to educate one resident. After completing the program, the trained resident performed spinal fusion surgery with robotic assistance under the supervision of a mentor. The clinical outcomes and learning curve associated with robotic surgery were then analyzed. RESULTS: Neurosurgical residents had limited opportunities to participate in spinal surgery during their training. Despite this, there was a significant interest in the emerging field of robotic surgery. A trained resident performed RASS under the supervision of a senior surgeon. A total of 166 screw insertions were attempted in 28 patients, with 2 screws failing due to skiving. According to the Gertzbein-Robbins classification, 85.54% of the screws were rated as grade A, 11.58% as grade B, 0.6% as grade C, and 1.2% as grade D. The clinical acceptance rate was approximately 96.99%, which is comparable to the results reported by senior experts and time per screw statistically significantly decreased as experience was gained. CONCLUSION: RASS can be performed with high accuracy within a relatively short timeframe, if residents receive adequate training.

Effectiveness of Live-Streaming Tele-Exercise Intervention in Patients With Parkinson's Disease: A Pilot Study.

OBJECTIVE: Exercise can improve both motor and nonmotor symptoms in people with Parkinson's disease (PwP), but there is an unmet need for accessible and sustainable exercise options. This study aimed to evaluate the effect, feasibility, and safety of a regularly performed live-streaming tele-exercise intervention for PwP. METHODS: A live-streaming exercise intervention for PwP was implemented twice a week for 12 weeks. We measured the motor and nonmotor symptom scores of the included patients before and after the intervention. Changes in clinical scores from baseline to postintervention were analyzed using paired t-tests. Factors associated with improvements in clinical scores and compliance were analyzed using Pearson's correlation analysis. RESULTS: Fifty-six participants were enrolled in the study. There were significant improvements in Hospital Anxiety and Depression Scale (HADS)-anxiety (p = 0.007), HADS-depression (p < 0.001), Unified Parkinson's Disease Rating Scale (UPDRS) part III (p < 0.001), UPDRS total (p = 0.015), Hoehn and Yahr stage (p = 0.027), and Parkinson's Disease Fatigue Scale-16 (p = 0.026) scores after the intervention. Improvements in motor symptoms were associated with improvements in mood symptoms and fatigue. Higher motor impairment at baseline was associated with a greater compliance rate and better postintervention composite motor and nonmotor outcomes (ΔUPDRS total score). Overall, the 12-week tele-exercise program was feasible and safe for PwP. No adverse events were reported. The overall adherence rate was 60.0% in our cohort, and 83.4% of the participants were able to participate in more than half of the exercise routines. CONCLUSION: The live-streaming tele-exercise intervention is a safe, feasible, and effective nonpharmacological treatment option that can alleviate fatigue and improve mood and motor symptoms in PwP.

A Comprehensive Analysis of Potential Complications after OLIF : A Review of Postoperative Magnetic Resonance Scans in Over 400 Cases.

Objective: This study focuses on identifying potential complications following oblique lumbar interbody fusion (OLIF) through routine magnetic resonance (MR) scans. Methods: From 650 patients who underwent OLIF from April 2018 to April 2022, this study included those with MR scans taken one-week post-operatively, and only for indirect decompression patients. The analysis evaluated postoperative MR images for hematoma, cage insertion angles, and indirect decompression efficiency. Patient demographics, post-operatively symptoms, and complications were also evaluated. Results: Out of 401 patients enrolled, most underwent 1- or 2-level OLIF. Common findings included approach site hematoma (65.3%) and contralateral psoas hematoma (19%). The caudal level OLIF was related with less orthogonality and deep insertion of cage. Incomplete indirect decompression occurred in 4.66% of cases but did not require additional surgery. Rare but symptomatic complications included remnant disc rupture (4 cases, 1%) and synovial cyst rupture (4 cases, 1%). Conclusion: This study has identified potential complications associated with OLIF, including approach site hematoma, contralateral psoas hematoma, cage malposition risk at caudal levels, and radiologically insufficient indirect decompression. Additionally, it highlights rare, yet symptomatic complications such as remnant disc rupture and synovial cyst rupture. These findings contribute insights into the relatively under-explored area of OLIF complications.

A Single-Center Experience of Robotic-Assisted Spine Surgery in Korea : Analysis of Screw Accuracy, Potential Risk Factor of Screw Malposition and Learning Curve.

OBJECTIVE: Recently, robotic-assisted spine surgery (RASS) has been considered a minimally invasive and relatively accurate method. In total, 495 robotic-assisted pedicle screw fixation (RAPSF) procedures were attempted on 100 patients during a 14-month period. The current study aimed to analyze the accuracy, potential risk factors, and learning curve of RAPSF. METHODS: This retrospective study evaluated the position of RAPSF using the Gertzbein and Robbins scale (GRS). The accuracy was analyzed using the ratio of the clinically acceptable group (GRS grades A and B), the dissatisfying group (GRS grades C, D, and E), and the Surgical Evaluation Assistant program. The RAPSF was divided into the no-breached group (GRS grade A) and breached group (GRS grades B, C, D, and E), and the potential risk factors of RAPSF were evaluated. The learning curve was analyzed by changes in robot-used time per screw and the occurrence tendency of breached and failed screws according to case accumulation. RESULTS: The clinically acceptable group in RAPSF was 98.12%. In the analysis using the Surgical Evaluation Assistant program, the tip offset was 2.37±1.89 mm, the tail offset was 3.09±1.90 mm, and the angular offset was 3.72°±2.72°. In the analysis of potential risk factors, the difference in screw fixation level (p=0.009) and segmental distance between the tracker and the instrumented level (p=0.001) between the no-breached and breached group were statistically significant, but not for the other factors. The mean difference between the no-breach and breach groups was statistically significant in terms of pedicle width (p<0.001) and tail offset (p=0.042). In the learning curve analysis, the occurrence of breached and failed screws and the robot-used time per screw screws showed a significant decreasing trend. CONCLUSION: In the current study, RAPSF was highly accurate and the specific potential risk factors were not identified. However, pedicle width was presumed to be related to breached screw. Meanwhile, the robot-used time per screw and the incidence of breached and failed screws decreased with the learning curve.

NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons.

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.

Fluorescent Phenotyping of Blood Cells Using a Differential Sensing Strategy: Differentiating Physiological Aging Stages and Neuro-Degenerative Disease Drugs.

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs.

Ankle and toe weakness caused by calcified ligamentum flavum cyst: A case report.

BACKGROUND: Ligamentum flavum cysts, which are most common in mobile junctional levels of the spine, can be a rare cause of spinal stenosis. There have been several case reports of ligamentum flavum cysts. However, there is yet to be a documented case report of a calcified ligamentum flavum cyst. Herein, we report the first case of a calcified ligamentum flavum cyst causing ankle and toe weakness. CASE SUMMARY: A 66-year-old male visited our hospital complaining of claudication as well as thigh and calf pain in his left leg, all beginning two weeks prior. Physical examination revealed motor weakness of the left ankle dorsiflexion and great toe dorsiflexion. Lumbar spinal computed tomography scans showed spinal stenosis combined with a calcified mass at the left side of the L4-5 level. Magnetic resonance imaging showed dural sac compression caused by the calcified mass at the left ligamentum flavum of the L4-5 level. We performed decompressive laminectomy and excision of the calcified mass combined with posterior lumbar interbody fusion at the L4-5 level. Intra-operatively, we found a firm and nodule like mass originating from the ventral surface of ligamentum flavum. Pathological examination suggested a calcified pseudocyst without a capsular lining. After the operation, the patient's motor weakness in the ankle and great toe improved gradually. CONCLUSION: The patient's ankle and great toe weakness were improved successfully after surgical removal of the calcified cyst.

Subjective cognitive complaints in patients with progressive supranuclear palsy.

Introduction: Subjective cognitive complaints (SCC) refer to self-reported cognitive decline that may or may not be reflected in objective neuropsychological evaluations. Such SCC are prevalent in neurodegenerative diseases, including Parkinson's disease (PD), but the prevalence and clinical features in patients with progressive supranuclear palsy (PSP) have not been investigated. Methods: We recruited 83 PSP patients without dementia and investigated their SCC using a semi-structured interview. Comprehensive neuropsychological test results and patient clinical features were compared according to presence of SCC and underlying cognitive state. Results: Among the 83 patients, 16 had normal cognition (NC), 67 had mild cognitive impairment (MCI), and 36 (43.4%) reported SCC. Among NC patients, 37.5% (6/16) had SCC, while 44.8% (30/67) of MCI patients reported SCC. There were no differences between the neuropsychological test results or demographic and clinical characteristics of PSP patients with or without SCC in the NC group. The demographic and clinical characteristics of the MCI+SCC (MCI with SCC)and MCI-SCC (MCI without SCC) groups were comparable, but the MCI+SCC group had significantly worse neuropsychological scores than the MCI-SCC group, particularly in tests assessing attention, language, visual memory, and fronto-executive function domains. Discussion: While SCC are commonly reported by PSP patients, patients with PSP and MCI+SCC had worse cognitive function than those who did not report SCC. These findings suggest that SCC in PSP patients with MCI could be a worsening sign of cognitive function. Therefore, it is crucial for physicians to assess SCC in PSP patients and to provide timely diagnosis and management of cognitive decline.

Application of Escherichia coli-Derived Recombinant Human Bone Morphogenic Protein-2 to Unstable Spinal Fractures.

(1) Background: Recently, Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E. coli-derived rhBMP-2) has been increasingly applied to different types of spinal surgeries and reported to achieve successful fusion. This pilot study aimed to evaluate the clinical efficacy and safety of rhBMP-2 in patients undergoing posterior instrumented fusions for unstable spinal fractures. (2) Methods: This study included ten consecutive patients undergoing spinal surgery using E. coli-derived rhBMP-2 with more than one year of follow-up. Radiologic outcomes were compared, including the average fracture healing period, local kyphosis correction, and clinical outcomes between preoperative and the last follow-up. (3) Results: The average time of radiographic union was 99.9 ± 45.4 (62-192) days, with an average use of 5.2 ± 3.9 months of anabolic agents. Radiologic parameters such as anterior vertebral height and vertebral wedge angle were significantly corrected postoperatively and at the last follow-up. Clinical outcomes other than leg pain were significantly improved after the surgery. In addition, four patients with preoperative neurologic deficits showed improved neurologic status. (4) Conclusions: Combined with the anabolic agents, applying E. coli-derived rhBMP-2 to the fractured vertebral body could be an effective surgical treatment for unstable spinal fractures. Further trials are needed to validate this result.

Inhibition of adipose tissue angiogenesis prevents rebound weight gain after caloric restriction in mice fed a high-fat diet.

AIMS: We investigated whether modulation of white adipose tissue (WAT) vasculature regulates rebound weight gain (RWG) after caloric restriction (CR) in mice fed a high-fat diet (HFD). MAIN METHODS: We compared changes in energy balance, hypothalamic neuropeptide gene expression, and characteristics of WAT by RT-qPCR, ELISA, immunohistochemistry, and adipose-derived stromal vascular fraction spheroid sprouting assay in obese mice fed a HFD ad libitum (HFD-AL), mice under 40 % CR for 3 or 4 weeks, mice fed HFD-AL for 3 days after CR (CRAL), and CRAL mice treated with TNP-470, an angiogenic inhibitor. KEY FINDINGS: WAT angiogenic genes were expressed at low levels, but WAT vascular density was maintained in the CR group compared to that in the HFD-AL group. The CRAL group showed RWG, fat regain, and hyperphagia with higher expression of angiogenic genes and reduced pericyte coverage of the endothelium in WAT on day 3 after CR compared to the CR group, indicating rapidly increased angiogenic activity after CR. Administration of TNP-470 suppressed RWG, fat regain, and hyperphagia only after CR compared to the CRAL group. Changes in circulating leptin levels and hypothalamic neuropeptide gene expression were correlated with changes in weight and fat mass, suggesting that TNP-470 suppressed hyperphagia independently of the hypothalamic melanocortin system. Additionally, TNP-470 increased gene expression related to thermogenesis, fuel utilization, and browning in brown adipose tissue (BAT) and WAT, indicating TNP-470-induced increase in thermogenesis. SIGNIFICANCE: Modulation of the WAT vasculature attenuates RWG after CR by suppressing hyperphagia and increasing BAT thermogenesis and WAT browning.

Evaluation of novel pyrazol-4-yl pyridine derivatives possessing arylsulfonamide tethers as c-Jun N-terminal kinase (JNK) inhibitors in leukemia cells.

A series of 36 pyrazol-4-yl pyridine derivatives (8a-i, 9a-i, 10a-i, and 11a-i) was designed, synthesized, and evaluated for its antiproliferative activity over NCI-60 cancer cell line panel and inhibitory effect against JNK isoforms (JNK1, JNK2, and JNK3). All the synthesized compounds were tested against the NCI-60 cancer cell line panel. Compounds 11b, 11c, 11g, and 11i were selected to determine their GI50s and exerted a superior potency over the reference standard SP600125 against the tested cell lines. 11c showed a GI50 of 1.28 µM against K562 leukemic cells. Vero cells were used to assess 11c cytotoxicity compared to the tested cancer cells. The target compounds were tested against hJNK isoforms in which compound 11e exhibited the highest potency against JNK isoforms with IC50 values of 1.81, 12.7, and 10.5 nM against JNK1, JNK2, and JNK3, respectively. Kinase profiling of 11e showed higher JNK selectivity in 50 kinase panels. Compounds 11c and 11e showed cell population arrest at the G2/M phase, induced early apoptosis, and slightly inhibited beclin-1 production at higher concentrations in K562 leukemia cells relative to SP600125. NanoBRET assay of 11e showed intracellular JNK1 inhibition with an IC50 of 2.81 µM. Also, it inhibited CYP2D6 and 3A4 with different extent and its hERG activity showed little cardiac toxicity with an IC50 of 4.82 µM. hJNK3 was used as a template to generate the hJNK1 crystal structure to explore the binding mode of 11e (PDB ID: 8ENJ) with a resolution of 2.8 °A and showed a typical type I kinase inhibition against hJNK1. Binding energy scores showed that selectivity of 11e towards JNK1 could be attributed to additional hydrophobic interactions relative to JNK3.

Incidental Ureteral Complication in Single-Center Consecutive Oblique Lateral Interbody Fusion Cases.

Oblique lateral interbody fusion (OLIF) has recently gained widespread use as a minimally invasive surgical procedure for degenerative lumbar disease. OLIF has several advantages but can also lead to several possible complications. For example, although less common, access through the retroperitoneal cavity can cause ureteral injury. Here, we report two cases of ureteral complications that occurred during consecutive OLIF procedures. One involved a 77-year-old female patient who had a double-J catheter inserted due to ureteral injury during surgery, and the other involved a 69-year-old male patient suspected of having a ureteral stricture due to retractor compression. To prevent ureteral complications in OLIF, it is necessary to accurately identify the anatomy of the ureter through preoperative imaging and to pay special attention during surgery.

Risk Factors for the Occurrence and Severity of Vertebral Fractures in Inflammatory Bowel Disease Patients: A Nationwide Population-Based Cohort Study.

BACKGROUND: The risk of vertebral fractures is increased in inflammatory bowel disease (IBD) patients. However, whether the severity of vertebral fractures differs between IBD patients and the general population, or between patients with Crohn's disease (CD) and ulcerative colitis (UC), is unknown. METHODS: We investigated risk factors associated with the occurrence and severity of vertebral fractures in IBD patients using The National Healthcare Insurance Service (NHIS) database. We defined the patients who underwent vertebroplasty or kyphoplasty after being diagnosed with a vertebral fracture as having a severe vertebral fracture than those with only diagnosis codes. RESULTS: From 2008 to 2018, there were 33,778 patients with IBD (24,370 UC patients and 9,408 CD patients) and 101,265 patients in the reference population. The incidence rate ratio of vertebral fractures in the IBD patients was 1.27 per 1,000 person-years (95% confidence interval [CI], 1.26-1.27). The risk of vertebral fracture was higher in CD and UC patients than in the matched reference group (hazard ratio [HR], 1.59; 95% CI, 1.31-1.92; P < 0.001 and HR, 1.26; 95% CI, 1.14-1.41; P < 0.001, respectively). In a multivariate analysis, the occurrence of vertebral fracture was associated with CD (HR, 1.31; 95% CI, 1.08-1.59; P = 0.006), older age (CD: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001 and UC: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001), female sex (CD: HR, 1.81; 95% CI, 1.63-2.01; P < 0.001 and UC: HR, 2.02; 95% CI, 1.83-2.22; P < 0.001), high Charlson Comorbidity Index (CCI) score (CD: HR, 1.42; 95% CI, 1.23-1.63; P < 0.001 and UC: HR, 1.46; 95% CI, 1.29-1.65, P < 0.001), and long-term steroid use (CD: HR, 3.71; 95% CI, 2.84-3.37; P < 0.001 and UC: HR, 3.88; 95% CI, 3.07-4.91; P < 0.001). The severity of vertebral fractures was associated with IBD (CD: HR, 1.82; 95% CI, 1.17-2.83; P = 0.008 and UC: HR, 1.49; 95% CI, 1.17-1.89; P < 0.001) and older age (HR, 1.06; 95% CI, 1.05-1.07; P < 0.001). CONCLUSION: Vertebral fractures occur frequently and more severely in IBD patients, particularly those with CD. Therefore, we suggest monitoring of bone density, regular vitamin D supply, and reducing the use of corticosteroids to prevent vertebral fractures in IBD patients who are older, female, or have comorbidities.

Mini-Open Intercostal Retroperitoneal Approach for Upper Lumbar Spine Lateral Interbody Fusion.

OBJECTIVE: Conventional oblique lumbar interbody fusion (OLIF) approach is possible from the L2/3 to L4/5 levels. However, obstruction of the lower ribs (10th-12th) makes it difficult to maintain disc parallel maneuvers or orthogonal maneuvers. To overcome these limitations, we proposed an intercostal retroperitoneal (ICRP) approach to access the upper lumbar spine. This method does not expose the parietal pleura or require rib resection and employs a small incision. METHODS: We enrolled patients who underwent a lateral interbody procedure on the upper lumbar spine (L1/2/3). We compared the incidence of endplate injury between conventional OLIF and ICRP approaches. In addition, by measuring the rib line, the difference in endplate injury according to rib location and approach was analyzed. We also analyzed the previous period (2018-2021) and the year 2022, when the ICRP has been actively applied. RESULTS: A total of 121 patients underwent lateral interbody fusion to the upper lumbar spine (OLIF approach, 99 patients; ICRP approach, 22 patients). Endplate injuries occurred in 34 of 99 (34.3%) and 2 of 22 patients (9.1%) during the conventional and ICRP approaches, respectively (p = 0.037; odds ratio, 5.23). When the rib line was located at the L2/3 disc or L3 body, the endplate injury rate was 52.6% (20 of 38) for the OLIF approach but 15.4% (2 of 13) for the ICRP approach. Since 2022, the proportion of OLIF including L1/2/3 levels has increased 2.9-fold. CONCLUSION: The ICRP approach is effective in reducing the incidence of endplate injury in patients with a relatively lower rib line, without pleural exposure or rib resection.

Metformin acts as a dual glucose regulator in mouse brain.

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain. Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed. Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption. Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis.