The Effect of Transpedicular Injection of Recombinant Human Bone Morphogenetic Protein-2/Beta-Tricalcium Phosphate Carrier on the Prevention of Proximal Junctional Kyphosis in Adult Spinal Deformity Surgery: A Pilot Study.

BACKGROUND AND OBJECTIVES: Several studies have explored strategies to prevent proximal junctional kyphosis (PJK) which is the unresolved issue in adult spinal deformity (ASD) surgery. This study aimed to investigate the preventive effects of upper instrumented vertebrae (UIV) recombinant human bone morphogenetic protein-2 (rhBMP-2) with beta-tricalcium phosphate (ß-TCP) carrier injection on PJK. METHODS: This study was conducted through a retrospective analysis of data collected both prospectively and retrospectively. In the rhBMP-2 group, consisting of 25 patients with ASD, rhBMP-2 along with ß-TCP carrier was administered to the UIV through the pedicle. To minimize time-related bias, control-1 included 66 patients who had undergone ASD surgery by the same surgeon in the year preceding the commencement of the study. Control-2 consisted of 63 patients who had undergone ASD surgery by the same surgeon during the year after the end of the study. The primary outcome is the occurrence of PJK within one year postsurgery, and the secondary outcome is the change in Hounsfield unit of the UIV one year after the surgery. RESULTS: When comparing baseline characteristics with control groups, a significant difference was observed only in body mass index, with control-1 (P = .006) and control-total (control-1 + control-2, P = .026) having a higher body mass index than the study group. In the rhBMP-2 group, there were 3 cases (PJK rate, 12.0%) of PJK, whereas control-1 and control-2 had 26 cases (PJK rate, 39.4%, P = .012) and 20 cases (PJK rate, 31.7%, P = .057), respectively. In the control-total, there were 46 cases (PJK rate, 35.7%, P = .020) of PJK. The UIV that received rhBMP-2 showed a statistically significant increase in Hounsfield unit measurements compared to preoperative values 1 year after surgery (P = .001). CONCLUSION: The transpedicular injection of rhBMP-2/ß-TCP carrier at the UIV significantly contributed to the prevention of PJK and effectively increased trabecular bone density at the UIV.

Effectiveness of a protein-supplemented very-low-calorie diet program for weight loss: a randomized controlled trial in South Korea.

Introduction: Weight-loss strategies through meal replacements are effective and sustainable options. However, few studies have assessed their effects on weight loss including body composition through protein-supplemented meal replacements targeting the Asian population, including Koreans. This study aimed to assess the effectiveness and safety of a protein-supplemented very-low-calorie diet (PSVLCD) for weight reduction and changes in body composition in individuals with obesity over a 12-month long-term period. Methods: In total, 106 participants with obesity were randomly assigned to a PSVLCD or control group (food-based calorie-restricted diet). Body weight, waist circumference, body composition, and blood marker levels were measured throughout the study. Statistical analyses were performed to compare outcomes between the groups. Results: Among the 106 participants, 84 completed the 12-month follow-up. Intention-to-treat analysis showed that the mean weight loss from baseline to 12 months was -6.86 kg (8.21% of baseline weight) in the PSVLCD group and - 4.66 kg (5.47% of initial body weight) in the control group; the difference was -2.20 kg with a marginally significant interval (95% confidence interval [CI], -4.90; 0.50). Waist circumference (-8.35 cm vs. -4.85 cm; mean difference, -3.49 cm; 95% CI, -6.48 to -0.50) and visceral fat area (-28.28 cm2 vs. -13.26 cm2; mean difference, -15.03cm2; 95% CI, -29.01 to -1.04) also significantly decreased in the PSVLCD group at 12 months. Discussion: The PSVLCD group demonstrated a substantial initial reduction in waist circumference that was sustained over the study period, alongside a marginally significant decrease in weight. These findings suggest that a protein-supplemented very-low-calorie diet may be an effective strategy for long-term weight management and body composition improvement in individuals with obesity. Clinical trial registration: ClinicalTrials.gov, identififer NCT04597788.

Liver-specific Coxsackievirus and adenovirus receptor deletion develop metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD.

Efficacy and Safety of Biportal Endoscopic Decompressive Laminectomy in Octogenarians With Severe Lumbar Spinal Stenosis.

BACKGROUND: Lumbar spinal stenosis (LSS) is prevalent among octogenarians, causing significant pain and disability. Surgical intervention is often required because of the ineffectiveness of conservative treatments. This study investigates the efficacy and safety of biportal endoscopic decompressive laminectomy (BED) in octogenarians with severe LSS, evaluating its potential as a minimally invasive surgical option. METHODS: This retrospective study included 107 patients aged 80 years or older who underwent BED for LSS between March 2017 and December 2022. Data were collected from electronic medical records, including demographic information, clinical outcomes, and surgical details. Patients with fractures, infectious spondylitis, herniated discs, and follow-up less than 12 months were excluded. Clinical outcomes were assessed using the visual analog scale, Oswestry Disability Index, European Quality of Life-5 Dimensions, and painDETECT at baseline and at 3, 6, and 12 months after surgery. RESULTS: The mean age of the 107 patients was 84.1 years, with 59% being women. Significant improvements were observed in visual analog scale scores for lower back and lower extremities pain, Oswestry Disability Index, European Quality of Life-5 Dimensions, and painDETECT scores, indicating reduced pain, decreased disability, and enhanced quality of life. There were no significant differences in outcomes between patients aged 80 to 84 and those 85 or older. Surgery-related outcomes such as operation time, blood loss, and complications were similar in both age groups. CONCLUSIONS: BED is a safe and effective treatment for LSS in octogenarians, providing significant pain relief and functional improvement. This minimally invasive technique is also viable for patients older than 85 years, without increased risk of complications, supporting its broader indications in managing LSS in the elderly. CLINICAL RELEVANCE: This study highlights the efficacy and safety of BED for LSS in octogenarians, demonstrating its potential to improve quality of life and function with low risks, making it a feasible option for elderly patients.

Evolutionarily divergent Mycobacterium tuberculosis CTP synthase filaments are under selective pressure.

The final and rate-limiting enzyme in pyrimidine biosynthesis, CTP synthase (CTPS) , is essential for the viability of Mycobacterium tuberculosis and other mycobacteria. Its product, CTP, is critical for RNA, DNA, lipid and cell wall synthesis, and is involved in chromosome segregation. In various organisms across the tree of life, CTPS assembles into higher-order filaments, leading us to hypothesize that M. tuberculosis CTPS (mtCTPS) also forms higher-order structures. Here, we show that mtCTPS does assemble into filaments but with an unusual architecture not seen in other organisms. Through a combination of structural, biochemical, and cellular techniques, we show that polymerization stabilizes the active conformation of the enzyme and resists product inhibition, potentially allowing for the highly localized production of CTP within the cell. Indeed, CTPS filaments localize near the CTP-dependent complex needed for chromosome segregation, and cells expressing mutant enzymes unable to polymerize are altered in their ability to robustly form this complex. Intriguingly, mutants that alter filament formation are under positive selection in clinical isolates of M. tuberculosis, pointing to a critical role needed to withstand pressures imposed by the host and/or antibiotics. Taken together, our data reveal an unexpected mechanism for the spatially organized production of a critical nucleotide in M. tuberculosis, which may represent a vulnerability of the pathogen that can be exploited with chemotherapy.

The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease.

The metal ion transporter SLC39A8 is associated with physiological traits and diseases, including blood manganese (Mn) levels and inflammatory bowel diseases (IBD). The mechanisms by which SLC39A8 controls Mn homeostasis and epithelial integrity remain elusive. Here, we generate Slc39a8 intestinal epithelial cell-specific-knockout (Slc39a8-IEC KO) mice, which display markedly decreased Mn levels in blood and most organs. Radiotracer studies reveal impaired intestinal absorption of dietary Mn in Slc39a8-IEC KO mice. SLC39A8 is localized to the apical membrane and mediates 54Mn uptake in intestinal organoid monolayer cultures. Unbiased transcriptomic analysis identifies alkaline ceramidase 1 (ACER1), a key enzyme in sphingolipid metabolism, as a potential therapeutic target for SLC39A8-associated IBDs. Importantly, treatment with an ACER1 inhibitor attenuates colitis in Slc39a8-IEC KO mice by remedying barrier dysfunction. Our results highlight the essential roles of SLC39A8 in intestinal Mn absorption and epithelial integrity and offer a therapeutic target for IBD associated with impaired Mn homeostasis.

Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Comparative Study on the Efficacy of Pregabalin Versus Limaprost in Patients With Lumbar Spinal Stenosis: A Prospective, Randomized Controlled Trial.

BACKGROUND: Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life (QoL) and also cause sleep disturbances. This study compares pregabalin and limaprost's efficacy in LSS for pain, disability, QoL, and sleep, aiming to offer insights for medication selection. METHODS: This study was designed as a prospective, randomized, single-center, single-blinded, clinical superiority trial targeting patients with LSS. For 6 weeks, 111 patients per group were administered medication following a standard regimen, after which patient-reported outcomes were measured. The primary outcome was the Visual Analogue Scale (VAS) for back and leg pain, and the secondary outcomes included the Oswestry Disability Index (ODI), European Quality of Life 5 Dimensions (EQ-5D), and sleep quality. RESULTS: After 6 weeks of medication, there were significant improvements over time in the primary outcome, VAS for back pain and leg pain, in both groups, but no significant difference between the 2 groups. Similarly, for the secondary outcomes, ODI and EQ-5D, both groups showed significant improvements, yet there was no significant difference between them. In the subgroup analysis targeting poor sleepers (Pittsburgh sleep quality index, PSQI >5), both groups also exhibited significant improvements in sleep quality, but again, there was no significant difference between the groups. CONCLUSIONS: Efficacy of pregabalin, limaprost in back and leg pain, ODI, EQ-5D, and sleep quality, but there was no significant difference between the 2 groups. Thus, it is advisable to prescribe based on individual drug responses and potential complications.

Higher Physical Activity is Associated with Reduced Lower Urinary Tract Symptoms in Korean Men.

PURPOSE: Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS. MATERIALS AND METHODS: A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms. RESULTS: The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72-0.97) for men engaging in 15-30 MET-hours per week, 0.82 (95% CI: 0.71-0.95) for 30-60 MET-hours per week, and 0.72 (95% CI: 0.62-0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01). CONCLUSIONS: A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.

Transpedicular injection of rhBMP-2 with ß-tricalcium phosphate to reduce the proximal junctional kyphosis after adult spinal deformity correction: preliminary study.

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.

Trends in underweight and severe underweight disparities in Korean adults and older adults: a nationwide, repeated cross-sectional study.

OBJECTIVES: Little is known about the disparities in underweight prevalence among the general population in high-income countries. We investigated the trends in underweight prevalence and disparities across sociodemographic groups among Korean adults and older adults. SETTING AND PARTICIPANTS: A series of cross-sectional data on Korean national health checkups for adults aged ≥20 years were analyzed from 2005 to 2016. MEASUREMENTS: Based on body mass index (kg/m2), underweight was graded as mild (17.0-18.49), moderate (16.0-16.9), and severe (<16.0). Underweight prevalence was compared across sociodemographic subgroups in 2015-2016. Trends in underweight disparities were examined from 2005-2006 to 2015-2016. Multivariable-adjusted odds ratios (ORs; 95% confidence intervals, CIs) were calculated using logistic regression. RESULTS: Approximately 11-22 million adults were included in each wave. In 2015-2016, the overall prevalence of underweight was 3.6% (men 2.0%, women 5.2%); severe underweight was 0.2% (men 0.1%, women 0.3%). The prevalence of underweight varied by sex and age groups. In men, those aged ≥80 years had the highest prevalence (overall 7.33%, severe underweight 0.84%). In women, those aged 20-29 years had the highest prevalence of overall underweight (14.57%), whereas those aged ≥80 years had the highest prevalence of severe underweight (1.38%). Compared with individuals in the lowest income quartile, men in the highest income had lower ORs of overall (0.59, 95% CI 0.59-0.60) and severe underweight (0.46, 95% CI 0.44-0.48); women in the highest income quartile had a higher OR of overall (1.12, 95% CI 1.12-1.13) but a lower OR of severe underweight (0.89, 95% CI 0.86-0.92). From 2005-2006 to 2015-2016, severe underweight consistently declined in older men but remained constant in women aged ≥80 years, widening sex disparities among older adults. Severe underweight decreased or leveled off in the highest income quartile but steadily increased in the lowest quartile, worsening income disparities. CONCLUSION: In this nationwide study, underweight was more prevalent among women, older adults aged ≥80 years, and low-income individuals. Disparities in severe underweight widened across sociodemographic subgroups over time.

Association between Chronic Atrophic Gastritis and Bone Mineral Density among Women Older than 40 Years of Age in Korea.

BACKGROUND: Chronic atrophic gastritis causes hypochlorhydria, hypergastrinemia, and malabsorption of nutrients, leading to lower bone mineral density. The few studies that investigated the association between chronic atrophic gastritis and bone mineral density have reported inconsistent findings. As such, the present study assessed the association between chronic atrophic gastritis and bone mineral density among a large sample of women >40 years of age in Korea. METHODS: Data from 8,748 women >40 years of age who underwent esophagogastroduodenoscopy and bone densitometry were analyzed. Chronic atrophic gastritis was diagnosed using esophagogastroduodenoscopy. Bone mineral density of the lumbar vertebrae (L), femur neck, and femur total, measured using dual-energy X-ray absorptiometry, were the primary outcome variables. Low bone mineral density, which could be diagnosed as osteoporosis or osteopenia, was defined and analyzed as a secondary outcome. Linear regression was used to calculate adjusted mean values of bone mineral density. The association between low bone mineral density and chronic atrophic gastritis was analyzed using multiple logistic regression. RESULTS: The adjusted mean bone mineral density for L1-L4 was 1.063±0.003, femur neck (0.826±0.002), and femur total (0.890±0.002) were significantly lower in patients with chronic atrophic gastritis than others (1.073±0.002, 0.836±0.001, 0.898±0.002, respectively; all P<0.01). Women with chronic atrophic gastritis exhibited an increased likelihood for osteopenia or osteoporosis, even after adjusting for age and other confounding factors (odds ratio, 1.25; 95% confidence interval, 1.13-1.40; P<0.01). However, subgroup analysis revealed statistical significance only in postmenopausal women (odds ratio, 1.27; P<0.001). CONCLUSION: Chronic atrophic gastritis was associated with lower bone mineral density and a higher risk for osteopenia or osteoporosis among postmenopausal women.

Optimal fabrication of a thin-film thermocouple (TFTC) using Alumel/chromel junctions.

Thin-film thermocouple (TFTC) technology is a novel measurement method that produces a thermocouple sensor during the deposition process, even though it is a complex surface, to obtain the surface temperature. TFTC is a thin film sensor for measuring temperature by contact methods, consisting of two different metals which can generate thermoelectric forces named "Seebeck effects". In the past decade there have been many attempts to measure the cutting temperature during machining processes using TFTF sensors. However, research has not yet progressed to optimize the sensor performance or fabrication process. This paper studies a preliminary technique for the fabrication of a TFTC sensor on a cutting tool surface and optimizes the deposition conditions, TFTC design, and sensor performance. Chromel and Alumel, which are materials commonly used in K-type thermocouples, were used for the thermal evaporation process. When the Chromel has a nickel to chrome ratio of 9:1, low resistivity and minimal variation with increasing temperature were observed. When the contact area of the deposited electrode (+) and (-) poles increased, the resistivity decreased and the TFTC sensitivity improved. Data acquisition tests using a DAQ system connected to the TFTC sensor show the lowest resistivity in TFTC B and C types are able to measure temperature data. It is expected that the heat generated during the cutting process can be detected using the TFTC sensor with B-type shape and Chromel with a 9:1 nickel to chrome ratio.

BMP-2-immobilized PCL 3D printing scaffold with a leaf-stacked structure as a physically and biologically activated bone graft.

Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.

Blood urea nitrogen to albumin ratio is associated with cerebral small vessel diseases.

Blood urea nitrogen (BUN) to albumin ratio (BAR) is a comprehensive parameter that reflects renal, inflammatory, nutritional, and endothelial functions. BAR has been shown to be associated with various cancers, pneumonia, sepsis, and pulmonary and cardiovascular diseases; however, few studies have been conducted on its association with cerebrovascular diseases. In this study, we evaluated the association between BAR and cerebral small vessel disease (cSVD) in health check-up participants. We assessed consecutive health check-up participants between January 2006 and December 2013. For the cSVD subtype, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of lacune and cerebral microbleeds (CMBs). The BAR was calculated by dividing BUN by albumin as follows: BAR = BUN (mg/dl)/albumin (g/dl). A total of 3012 participants were evaluated. In multivariable linear regression analysis, BAR showed a statistically significant association with WMH volume after adjusting for confounders [ß = 0.076, 95% confidence interval (CI): 0.027-0.125]. In multivariable logistic regression analyses, BAR was significantly associated with lacunes [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.00-1.44] and CMBs (aOR = 1.28, 95% CI: 1.06-1.55). BAR was associated with all types of cSVD in the health check-up participants.

Monocyte to high-density lipoprotein cholesterol ratio is associated with cerebral small vessel diseases.

BACKGROUND: Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants. METHODS: This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 103/µL) / HDL cholesterol (mmol/L). RESULTS: In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [ß = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07-1.91], and CMB (aOR = 1.51, 95% CI = 1.03-2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH (P < 0.001), lacunes (P < 0.001), and CMBs (P < 0.001). CONCLUSIONS: High MHR was closely associated with cSVD in health check-up participants. Because these associations appear across all cSVD subtypes, inflammation appears to be a major pathological mechanism in the development of various cSVDs.

Feasibility and Effectiveness of a Ring-Type Blood Pressure Measurement Device Compared With 24-Hour Ambulatory Blood Pressure Monitoring Device.

BACKGROUNDS AND OBJECTIVES: This study aimed to evaluate the applicability and precision of a ring-type cuffless blood pressure (BP) measurement device, CART-I Plus, compared to conventional 24-hour ambulatory BP monitoring (ABPM). METHODS: Forty patients were recruited, and 33 participants were included in the final analysis. Each participant wore both CART-I Plus and ABPM devices on the same arm for approximately 24 hours. BP estimation from CART-I Plus, derived from photoplethysmography (PPG) signals, were compared with the corresponding ABPM measurements. RESULTS: The CART-I Plus recorded systolic blood pressure (SBP)/diastolic blood pressure (DBP) values of 131.4±14.1/81.1±12.0, 132.7±13.9/81.9±11.9, and 128.7±14.6/79.3±12.2 mmHg for 24-hour, daytime, and nighttime periods respectively, compared to ABPM values of 129.7±11.7/84.4±11.2, 131.9±11.6/86.3±11.1, and 124.5±13.6/80.0±12.2 mmHg. Mean differences in SBP/DBP between the two devices were 1.74±6.69/-3.24±6.51 mmHg, 0.75±7.44/-4.41±7.42 mmHg, and 4.15±6.15/-0.67±5.23 mmHg for 24-hour, daytime, and nighttime periods respectively. Strong correlations were also observed between the devices, with r=0.725 and r=0.750 for transitions in SBP and DBP from daytime to nighttime, respectively (both p<0.001). CONCLUSIONS: The CART-I Plus device, with its unique ring-type design, shows promising accuracy in BP estimation and offers a potential avenue for continuous BP monitoring in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06084065.

Comparative Study of Post-Surgical Outcomes in Pain, Disability, and Health-Related Quality of Life for Adult Spinal Deformity in Patients Aged above and below 75 Years.

(1) Background: Adult spinal deformity (ASD) surgery is known to improve clinical and radiological parameters; however, it may also cause more complications in elderly patients. The purpose of this study was to compare the outcomes of ASD surgery, specifically regarding pain, disability, and health-related quality of life (HRQOL) in patients aged 75 years and over and patients aged under 75 years; (2) Methods: A total of 151 patients who underwent ASD surgery between August 2014 and September 2020 were included. Patients were divided into two groups based on whether they are 75 years and over or under. Radiological parameters measured included sagittal vertical axis (SVA), pelvic tilt (PT), and pelvic incidence (PI)- lumbar lordosis (LL). Data were collected 3, 6, and 12 months after surgery; (3) Results: At 12 months postoperatively, visual analog scale (VAS) for low back pain (p = 0.342), Oswestry disability index (ODI) (p = 0.087), and EuroQol 5-Dimensions (EQ-5D) (p = 0.125) did not differ between patients under 75 years and those 75 and above 75 group. PT (p = 0.675), PI-LL (p = 0.948), and SVA (p = 0.108) did not differ significantly 12 months after surgery in the two groups. In the entire patient group, compared to preoperative data, significant improvements were demonstrated for clinical and radiological parameters 12 months after surgery (all p < 0.001). The rate of medical complications did not correlate with age, but the rates of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) did (p = 0.638, p < 0.001, and p = 0.001, respectively); (4) Conclusions: In terms of clinical and radiological improvements, ASD surgery should be considered for patients regardless of whether they are younger than or older than 75 years. The clinical and radiological improvements and the risk of complications and revision surgeries must be considered in ASD patients who are 75 years or older.

Effects of myeloid immune cells on the metabolic process of biomimetic bone regeneration.

AIMS: As the process of bone regeneration is preceded by an inflammatory response, the immune system has long been considered important for fracture healing. Despite many studies on the contribution of immune cells to bone-related diseases, the role of immune cells in the regeneration therapy of lost bone is not well understood. In addition, various types of cells are involved in the clinical bone regeneration environment, but most of the osteo-biology studies are conducted in an osteoblast-only environment. MATERIALS AND METHODS: Here, we investigated the effects of macrophages and dendritic cells on osteogenic differentiation in a co-culture environment involving human periosteal cell-derived osteoblasts, human monocyte-derived osteoclasts, and myeloid-derived cells. In addition, the cluster of myeloid immune cells involved in the clinical bone regeneration process was analyzed through bone defect rat modeling. KEY FINDINGS: We found that specific types of myeloid cells and related cytokines increased osteogenic differentiation. These results were confirmed in experiments using myeloid cells originating from human primitive peripheral blood mononuclear cells and by measuring the colonization of macrophages and dendritic cells in an in vivo bone defect environment. In addition, Next generation sequencing (NGS) analysis was performed through RNA sequencing for osteogenesis caused by macrophages and dendritic cells in vitro, which implemented a clinical bone regeneration environment. The results of these experiments suggest that the role of M2 macrophages or dendritic cells is markedly increased during osteogenic differentiation. Therefore, we propose that the exchange of bioactive factors between macrophages and dendritic cells during the bone formation metabolic process is a crucial step of tissue regeneration rather than limited to the initial inflammatory response. SIGNIFICANCE: This study indicates that M2 macrophages, among myeloid cells, can be mediators that play a vital role in the effective bone regeneration process and shows the potential as a useful next-generation advanced cell therapy for bone regeneration treatment.