Osteoporosis, spinal degenerative disorders, and their association with low back pain, activities of daily living, and physical performance in a general population.

Osteoporosis, vertebral fractures, and spinal degenerative diseases are common conditions that often coexist in older adults. This study aimed to determine the factors influencing low back pain and its impact on activities of daily living (ADL) and physical performance in older individuals with multiple comorbidities. This cross-sectional study was part of a large-scale population-based cohort study in Japan, involving 1009 participants who underwent spinal magnetic resonance imaging (MRI) to assess cervical cord compression, radiographic lumbar spinal stenosis, and lumbar disc degeneration. Vertebral fractures in the thoracolumbar spine were evaluated using sagittal MRI with a semi-quantitative method. Bone mineral density was measured using dual-energy X-ray absorptiometry. Low back pain, Oswestry Disability Index (ODI), and physical performance tests, such as one-leg standing time, five times chair-stand time, maximum walking speed, and maximum step length, were assessed. Using clinical conditions as objective variables and image evaluation parameters as explanatory variables, multiple regression analysis showed that vertebral fractures were significantly associated with low back pain and ODI. Vertebral fractures and osteoporosis significantly impacted physical performance, whereas osteoporosis alone did not affect low back pain or ODI. Our findings contribute to new insights into low back pain and its impact on ADL and physical performance.

A method for evaluating hunger and thirst in monkeys by measuring blood ghrelin and osmolality levels.

Hunger and thirst drive animals' consumption behavior and regulate their decision-making concerning rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and examined how these thirst states influenced their risk-taking behaviour in decisions involving fluid rewards. However, hunger assessment in monkeys remains poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate performance, it remains unclear how these two physiological needs are satisfied in captive monkeys. Here, we measured blood ghrelin and osmolality levels to respectively assess hunger and thirst in four captive macaques. Using an enzyme-linked immunosorbent assay, we identified that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access (with ad libitum water). This reflects a typical controlled food access condition. One hour after consuming a regular dry meal, the blood ghrelin levels in three out of four monkeys decreased to within their baseline range. Additionally, blood osmolality measured from the same blood sample, the standard hematological index of hydration status, increased after consuming the regular dry meal with no water access. Thus, ghrelin and osmolality may reflect the physiological states of individual monkeys regarding hunger and thirst, suggesting that these indices can be used as tools for monitoring hunger and thirst levels that mediate an animal's decision to consume rewards.Significance statement Standard methods for behavioral and neurophysiological experiments in non-human primates rely on controlled access to food or fluid rewards to motivate their performance. We previously assessed the thirst state of monkeys by measuring blood osmolality, the most widely used hematological index of hydration status. Here, we assessed the hunger state of monkeys by measuring blood ghrelin levels, a widely measured hunger-related peptide hormone in humans, using an enzyme-linked immunosorbent assay. We measured these indices and found that they reflected the hunger and thirst states of the monkeys before and after consuming dry meals, with no relation to each other. Thus, these two physical indices can be utilized to monitor hunger and thirst in primates.

Low pre-infection levels of neutralizing antibody in breakthrough infections after bivalent BA.4-5 vaccine and practical application of dried blood spots.

The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4-5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50 % using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4-5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation.

A longitudinal population-based study identifies THBS2 as a susceptibility gene for intervertebral disc degeneration.

PURPOSE: Intervertebral disc degeneration (IDD) is a common degenerative disease associated with ageing. Additionally, IDD is recognized as one of the leading causes of low back pain and disability in the working-age population and is the first step in the process leading to degenerative spinal changes. However, the genetic factors and regulatory mechanisms of IDD remain unknown. Therefore, we selected eight single nucleotide polymorphisms of genes to reveal the progression of IDD in a 7-year longitudinal study of the general population in Japan. METHODS: IDD was evaluated in the Wakayama Spine Study (WSS), which is a population-based cohort study. Overall, 574 participants from the general population cohort who underwent whole spine magnetic resonance imaging and provided clinical information were included in this longitudinal survey. RESULTS: The progression of IDD was affected only by THBS2 at the lumbar region, T12-L1 (p = 0.0044) and L3-4 (p = 0.0045). The significant interaction between THBS2 and age with IDD negatively affected the thoracic spines and passively influenced both the thoracolumbar junction and thoracic spines. The higher progression per year of Pfirrmann's score was rapid in young people with age; however, this decelerated the IDD progression per year in different ages. CONCLUSION: Our longitudinal study found the genes associated with IDD progression and that genetic factors' impact on IDD differs depending on disc level and age.

The microtubule-dynamin binding inhibitor peptide PHDP5 rescues spatial learning and memory deficits in Alzheimer's disease model mice.

Dynamin is a microtubule (MT) binding protein playing a key role in vesicle endocytosis. In a brain slice model, tau loaded in presynaptic terminals assembles MTs, thereby impairing vesicle endocytosis via depletion of cytosolic dynamin. The peptide PHDP5, derived from the pleckstrin homology domain of dynamin 1, inhibits dynamin-MT interaction and rescues endocytosis and synaptic transmission impaired by tau when co-loaded in presynaptic terminals. We tested whether in vivo administration of PHDP5 could rescue the learning/memory deficits observed in Alzheimer's disease (AD) model mice. A modified PHDP5 incorporating a cell-penetrating peptide (CPP) and a FITC fluorescent marker was delivered intranasally to Tau609 transgenic (Tg) and 3xTg-AD mice. FITC-positive puncta were observed in the hippocampus of mice infused with PHDP5 or scrambled (SPHDP5) peptide, but not in saline-infused controls. In the Morris water maze (MWM) test for spatial learning/memory, AD model mice treated with FITC-PHDP5-CPP showed prominent improvements in learning and memory, performing close to the level of saline-infused WT mice control. In contrast, mice treated with a scrambled construct (FITC-SPHDP5-CPP) showed no significant improvement. We conclude that PHDP5 can be a candidate for human AD therapy.

High interleukin-6 levels induced by COVID-19 pneumonia correlate with increased circulating follicular helper T cell frequency and strong neutralization antibody response in the acute phase of Omicron breakthrough infection.

Background: Acute immune responses to coronavirus disease 2019 (COVID-19) are influenced by variants, vaccination, and clinical severity. Thus, the outcome of these responses may differ between vaccinated and unvaccinated patients and those with and without COVID-19-related pneumonia. In this study, these differences during infection with the Omicron variant were investigated. Methods: A total of 67 patients (including 47 vaccinated and 20 unvaccinated patients) who were hospitalized within 5 days after COVID-19 symptom onset were enrolled in this prospective observational study. Serum neutralizing activity was evaluated using a pseudotyped virus assay and serum cytokines and chemokines were measured. Circulating follicular helper T cell (cTfh) frequencies were evaluated using flow cytometry. Results: Twenty-five patients developed COVID-19 pneumonia on hospitalization. Although the neutralizing activities against wild-type and Delta variants were higher in the vaccinated group, those against the Omicron variant as well as the frequency of developing pneumonia were comparable between the vaccinated and unvaccinated groups. IL-6 and CXCL10 levels were higher in patients with pneumonia than in those without it, regardless of their vaccination status. Neutralizing activity against the Omicron variant were higher in vaccinated patients with pneumonia than in those without it. Moreover, a distinctive correlation between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions was observed only in vaccinated patients. Conclusions: The present study demonstrates the existence of a characteristic relationship between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions in Omicron breakthrough infection.

Accurate fall risk classification in elderly using one gait cycle data and machine learning.

BACKGROUND: Falls among the elderly are a major societal problem. While observations of medium-distance walking using inertial sensors identified potential fall predictors, classifying individuals at risk based on single gait cycles remains elusive. This challenge stems from individual variability and step-to-step fluctuations, making accurate classification difficult. METHODS: We recruited 44 participants, equally divided into high and low fall-risk groups. A smartphone secured on their second sacral spinous process recorded data during indoor walking. Features were extracted at each gait cycle from a 6-dimensional time series (tri-axial angular velocity and tri-axial acceleration) and classified using the gradient boosting decision tree algorithm. FINDINGS: Mean accuracy across five-fold cross-validation was 0.936. "Age" was the most influential individual feature, while features related to acceleration in the gait direction held the highest total relative importance when aggregated by axis (0.5365). INTERPRETATION: Combining acceleration, angular velocity data, and the gradient boosting decision tree algorithm enabled accurate fall risk classification in the elderly, previously challenging due to lack of discernible features. We reveal the first-ever identification of three-dimensional pelvic motion characteristics during single gait cycles in the high-risk group. This novel method, requiring only one gait cycle, is valuable for individuals with physical limitations hindering repetitive or long-distance walking or for use in spaces with limited walking areas. Additionally, utilizing readily available smartphones instead of dedicated equipment has potential to improve gait analysis accessibility.

Long-term efficacy of microendoscopic laminotomy for lumbar spinal stenosis in advanced degenerative spondylolisthesis with or without dynamic spinal instability: a propensity score-matching analysis.

OBJECTIVE: In this study, the authors aimed to determine the mid- to long-term outcomes of microendoscopic laminotomy (MEL) for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) and identify preoperative predictors of poor mid- to long-term outcomes. METHODS: The authors retrospectively reviewed the medical records of 274 patients who underwent spinal MEL for symptomatic LSS. The minimum postoperative follow-up duration was 5 years. Patients were classified into two groups according to DS: those with DS (the DS+ group) and those without DS (the DS- group). The patients were subjected to propensity score matching based on sex, age, BMI, surgical segments, and preoperative leg pain visual analog scale scores. Clinical outcomes were evaluated 1 year and > 5 years after surgery. RESULTS: Surgical outcomes of MEL for LSS were not significantly different between the DS+ and DS- groups at the final follow-up (mean 7.8 years) in terms of Oswestry Disability Index (p = 0.498), satisfaction (p = 0.913), and reoperation rate (p = 0.154). In the multivariate analysis, female sex (standard ß -0.260), patients with slip angle > 5° in the forward bending position (standard ß -0.313), and those with dynamic progression of Meyerding grade (standard ß -0.325) were at a high risk of poor long-term outcomes. CONCLUSIONS: MEL may have good long-term results in patients with DS without dynamic instability. Women with dynamic instability may require additional fusion surgery in approximately 25% of cases for a period of ≥ 5 years.

Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method.

Mitochondrial toxicity has been implicated in the development of various toxicities, including hepatotoxicity. Therefore, mitochondrial toxicity has become a major screening factor in the early discovery phase of drug development. Several models have been developed to predict mitochondrial toxicity based on chemical structures. However, they only provide a binary classification of positive or negative results and do not provide the substructures that contribute to a positive decision. Therefore, we developed an artificial intelligence (AI) model to predict mitochondrial toxicity and visualize structural alerts. To construct the model, we used the open-source software library kMoL, which employs a graph neural network approach that allows learning from chemical structure data. We also utilized the integrated gradient method, which enables the visualization of substructures that contribute to positive results. The dataset used to construct the AI model exhibited a significant imbalance, with significantly more negative than positive data. To address this, we employed the bagging method, which resulted in a model with high predictive performance, as evidenced by an F1 score of 0.839. This model can also be used to visualize substructures that contribute to mitochondrial toxicity using the integrated gradient method. Our AI model predicts mitochondrial toxicity based on chemical structures and may contribute to screening mitochondrial toxicity in the early stages of drug discovery.

Influence of Orthodontic Treatment on Changes in the Maxillary Sinus Dimensions.

Objective This study aimed to investigate the correlation of craniofacial morphology with maxillary sinus morphology and to evaluate whether orthodontic treatment facilitates maxillary sinus enlargement in adults. Materials and methods A total of 45 adult women underwent cephalography and computed tomography before and after orthodontic treatment. All participants were classified into three groups: skeletal class I, II, and III. The average dimensions and volume of the maxillary sinus were calculated in each subgroup. Furthermore, multiple regression analysis was used to analyze the correlations of maxillary sinus dimensions with 20 cephalometric variables. Results Before treatment, the maxillary sinus width, height, depth, and volume were 32.2 ± 3.9 mm, 39.5 ± 3.8 mm, 38.6 ± 1.8 mm, and 36,179.3 ± 5,454.0 mm3 in skeletal class I, 33.9 ± 6.2 mm, 37.3 ± 3.5 mm, 38.6 ± 2.4 mm, and 34,729.8 ± 6,686.6 mm3 in skeletal class II, and 32.0 ± 4.3 mm, 41.8 ± 5.0 mm, 38.0 ± 2.8 mm, and 35,592.3 ± 10,334.3 mm3 in skeletal class III, respectively. Despite no significant differences in maxillary sinus width, depth, or volume, the height was significantly lower in the skeletal class II than in the other two. Regardless of the skeletal pattern, maxillary sinus height and volume increased considerably after treatment. Moreover, the maxillary sinus width was substantially involved in pretreatment U1 to SN and overbite and posttreatment U1 to NA and overjet. Conclusion Except for the height, the maxillary sinus dimensions were almost similar, irrespective of the skeletal classification. The posttreatment sinus height and volume were significantly greater than the pretreatment values, although the sinus width and length showed no significant changes during orthodontic treatment. This implies that orthodontic treatment may facilitate the enlargement of the maxillary sinus even after physical growth.

Benefits of surgical treatment within 48†h of proximal femoral fracture in centenarians: a retrospective cohort study.

Introduction: Proximal femoral fractures in aging populations represent a significant concern, with an increasing prevalence among individuals aged ≥100 years. The existing research does not provide robust guidance for clinicians managing older patients aged ≥100 years with proximal femoral fractures. We investigated the safety and efficacy of surgical treatment in patients aged ≥100 years with proximal femoral fractures and evaluated the impact of early surgery on their outcomes. Methods: This retrospective cohort study involved 15 patients aged ≥100 years who underwent surgical treatment of proximal femoral fractures; the control group included 137 patients in their 90s. Data were collected between January 2010 and December 2017. Evaluation items included patient characteristics, surgical details, perioperative complication rates, length of hospital stay, the proportion of patients discharged to the same facility or home, rate of regaining walking ability, and 1-year survival rate. Results: The patients aged ≥100 years and those in their 90s had comparable outcomes. Thus, age alone does not dictate surgical success. Early surgery (≤48 h) was associated with trends toward improved perioperative complications, ambulatory ability, and return to original living environment. Discussion: This study underscores the potential benefits of surgical intervention for proximal femoral fractures in patients aged ≥100 years, indicating the relevance of early surgery (≤48 h). Our findings emphasized the importance of timely intervention and evidence-based decision-making for this demographic. Clinicians, policymakers, and patients could benefit from our insights to enhance fracture management strategies, along with future research endeavors to validate and expand our results in larger multicenter cohorts.

Conjoined lumbosacral nerve root: a case report.

BACKGROUND: In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. CASE PRESENTATION: We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5-S disc degeneration. L5-S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. CONCLUSIONS: This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root.

The fatal case of "Pigmentibacter" bacteremia following aspiration pneumonia in elderly patient.

"Pigmentibacter ruber" was first reported in 2021, a novel bacterium of the family Silvanigrellaceae, isolated from human blood of the patient with aspiration pneumonia after the drowning accident in Republic of China. However, until now, there is only one report describing "P. ruber" infection, and no case of isolation from natural environment has been reported so far. Thus, the infectivity and pathogenicity of "Pigmentibacter" spp. has not been clearly understood. In this report, we described the fatal case of "Pigmentibacter" bacteremia subsequently occurred after aspiration pneumonia probably due to accidental ingestion of irrigation water in the elderly patient. Despite administration of broad-spectrum antibiotic, the patient dramatically deteriorated and eventually deceased. Whole-genome sequencing showed the strain isolated from the patient was identified as "Pigmentibacter" sp. (designated as strain Takaoka) and antimicrobial sensitivity testing showed it displayed high minimum inhibitory concentrations against various antibiotics including ß-lactam. Further studies are needed to clarify the clinical characteristics of "Pigmentibacter" and its relative's infections and their antimicrobial sensitivity; however, the present case supported the clinical characteristics of "Pigmentibacter" infection, which can lead to bacteremia following aspiration pneumonia caused by mis-swallowing contaminated water, and poor outcome potentially due to multidrug resistances.

High-Fat Diet Induced PPARδ Promotes Self-renewal of Preleukemic Progenitors in Development of Acute Promyelocytic Leukemia.

From risk association between acute promyelocytic leukemia (APL) and obese-overweight individuals, Mazzarella and colleagues hypothesized that a high-fat diet (HFD) promotes development of APL. Using mouse APL model (PML-RARα knock-in), the authors demonstrated that linoleic acid drives activation of PPARδ in hematopoietic progenitors, and that activation of PPARδ increases proliferation of progenitor cells with PML-RARA expression toward APL. Involvements of PPARδ on regulation of stem cell renewal and proliferation were shown in colorectal cancers earlier, but this study newly demonstrates in hematopoietic progenitors, while suggesting use of diet rich in linoleic acid with caution. See related article by Mazzarella et al., p. 59.

Methylglyoxal activates transient receptor potential A1/V1 via reactive oxygen species in the spinal dorsal horn.

Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.

Long-term Outcomes After Adult Spinal Deformity Surgery Using Lateral Interbody Fusion: Short Versus Long Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate long-term outcomes after short or long fusion for adult spinal deformity using lateral interbody fusion. SUMMARY OF BACKGROUND DATA: Lateral interbody fusion is commonly used in adult spinal deformity surgery. Favorable short-term outcomes have been reported, but not long-term outcomes. Lateral interbody fusion with strong ability to correct deformity may allow the selection of short fusion techniques. MATERIALS AND METHODS: We retrospectively reviewed adults who underwent this surgery with a minimum of 5 years of follow-up. Short fusion with the uppermost instrumented vertebra in the lumbar spine was performed in patients without degenerative changes at the thoracolumbar junction (S-group); others underwent long fusion with the uppermost instrumented vertebra in the thoracic spine (L-group). We assessed radiographic and clinical outcomes. RESULTS: Short fusion was performed in 29 of 54 patients. One patient per group required revision surgery. Of the remainder, with similar preoperative characteristics and deformity correction between groups, correction loss (pelvic incidence-lumbar lordosis, P=0.003; pelvic tilt, P=0.005; sagittal vertical axis, P˂0.001) occurred within 2 years postoperatively in the S-group, and sagittal vertical axis continued to increase until the 5-year follow-up (P=0.021). Although there was a significant change in Oswestry disability index in the S-group (P=0.031) and self-image of Scoliosis Research Society 22r score in both groups (P=0.045 and 0.02) from 2- to 5-year follow-up, minimum clinically important differences were not reached. At 5-year follow-up, there was a significant difference in Oswestry Disability Index (P=0.013) and Scoliosis Research Society 22r scores (function: P=0.028; pain: P=0.003; subtotal: P=0.006) between the groups, but satisfaction scores were comparable and Oswestry Disability Index score (29.8%) in the S-group indicated moderate disability. CONCLUSIONS: Health-related quality of life was maintained between 2- and 5-year follow-up in both groups. Short fusion may be an option for patients without degenerative changes at the thoracolumbar junction. LEVEL OF EVIDENCE: III.

Factors associated with cam deformity in Japanese local residents.

Femoroacetabular impingement has increasingly been recognized as a cause of primary hip osteoarthritis; however, its epidemiological indications remain unclear. We aimed to clarify the epidemiological indications and factors associated with cam deformity in a large-scale population-based cohort in Japan. Overall, 1480 participants (2960 hips) (491 men, 989 women; mean age, 65.3 years) analyzed in the third survey of the Research on Osteoarthritis/Osteoporosis Against Disability study were included. The α angle and spinopelvic parameters (lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence) were radiographically measured. Cam deformity was defined as α angle ≥ 60°. Overall, the cam deformity prevalence was 147/2960 (5.0%). Cam deformity prevalence tended to increase with age; in the univariate analysis, a higher percentage of men was observed in the group with cam deformity than in the group without it. No relationship was observed between cam deformity and hip pain. Factors associated with α angle were examined via multiple regression analysis for each gender; α angle was significantly associated with age and BMI in each gender. The α angle and PT were correlated in women. Thus, α angle and cam deformity prevalence increase with age in Japanese individuals. Accordingly, cam deformity can be considered a developmental disease.

Outcomes and Vertebral Osteophytes and Bulging Intervertebral Discs Occupancy as a Decision-Making Tool for Surgical Success in Patients Undergoing Microendoscopic Foraminotomy for Lumbar Foraminal Stenosis.

OBJECTIVE: The objective of this study was to determine the long-term outcomes of microendoscopic foraminotomy in treating lumbar foraminal stenosis and identify the optimal extent of decompression that yields improved results and fewer complications. METHODS: A retrospective cohort study reviewed the medical records of 95 consecutive patients who underwent microendoscopic foraminotomy for lumbar foraminal stenosis. Clinical outcomes were assessed using the Japanese Orthopaedic Association scoring system and visual analog scale for low back and leg pain. Surgical success was determined by meeting significant improvement thresholds for back and leg pain at 2 years postoperatively. Multiple regression analysis identified factors associated with improved pain scores. Receiver operating characteristic curve analysis determined the cut-off values for successful surgeries. RESULTS: Significant improvements were observed in Japanese Orthopaedic Association and visual analog scale scores for back and leg pain 2 years postoperatively compared with preoperative scores (P < 0.0001) and sustained over a ≥5-year follow-up period. Reoperation rates were low and did not significantly increase over time. Multiple regression analysis identified occupancy of the vertebral osteophytes and bulging intervertebral discs (O/D complex) as surgical success predictors. A 45.0% O/D complex occupancy cutoff value was determined, displaying high sensitivity and specificity for predicting surgical success. CONCLUSIONS: This study provides evidence supporting the long-term efficacy of microendoscopic foraminotomy for lumbar foraminal stenosis and predicting surgical success. The 45.0% O/D complex occupancy cut-off value can guide patient selection and outcome prediction. These insights contribute to informed surgical decision-making and underscore the importance of evaluating the O/D complex in preoperative planning and predicting outcomes.

Prevalence and distribution of Schmorl node and endplate signal change, and correlation with disc degeneration in a population-based cohort: the Wakayama Spine Study.

PURPOSE: Degenerative spinal conditions, including disc degeneration (DD), Schmorl nodes (SN), and endplate signal changes (ESC), are pervasive age-associated phenomena that critically affect spinal health. Despite their prevalence, a comprehensive exploration of their distribution and correlations is lacking. This study examined the prevalence, distribution, and correlation of DD, SN, and ESC across the entire spine in a population-based cohort. METHODS: The Wakayama Spine Study included 975 participants (324 men, mean age 67.2 years; 651 women, mean age 66.0 years). Magnetic resonance imaging (MRI) was used to evaluate the intervertebral space from C2/3 to L5/S1. DD was classified using Pfirrmann's system, ESC was identified by diffuse high-intensity signal changes on the endplates, and SN was defined as a herniation pit with a hypointense signal. We assessed the prevalence and distribution of SN, ESC, and DD across the entire spine. The correlations among these factors were examined. RESULTS: Prevalence of ≥ 1 SN over the entire spine was 71% in men and 77% in women, while prevalence of ≥ 1 ESC was 57.9% in men and 56.3% in women. The prevalence of ESC and SN in the thoracic region was the highest among the three regions in both sexes. Positive linear correlations were observed between the number of SN and DD (r = 0.41, p < 0.001) and the number of ESC and DD (r = 0.40, p < 0.001), but weak correlations were found between the number of SN and ESC (r = 0.29, p < 0.001). CONCLUSION: The prevalence and distribution of SN and ESC over the entire spine were observed, and correlations between SN, ESC, and DD were established. This population-based cohort study provides a comprehensive analysis of these factors.

Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.

Irgb6 is a priming immune-related GTPase (IRG) that counteracts Toxoplasma gondii. It is known to be recruited to the low virulent type II T. gondii parasitophorous vacuole (PV), initiating cell-autonomous immunity. However, the molecular mechanism by which immunity-related GTPases become inactivated after the parasite infection remains obscure. Here, we found that Thr95 of Irgb6 is prominently phosphorylated in response to low virulent type II T. gondii infection. We observed that a phosphomimetic T95D mutation in Irgb6 impaired its localization to the PV and exhibited reduced GTPase activity in vitro. Structural analysis unveiled an atypical conformation of nucleotide-free Irgb6-T95D, resulting from a conformational change in the G-domain that allosterically modified the PV membrane-binding interface. In silico docking corroborated the disruption of the physiological membrane binding site. These findings provide novel insights into a T. gondii-induced allosteric inactivation mechanism of Irgb6.