Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Non-Synonymous Substitutions in Cadherin 13, Solute Carrier Family 6 Member 4, and Monoamine Oxidase A Genes are Associated with Personality Traits in Thoroughbred Horses.

Retraining retired racehorses for various purposes can help correct behavioral issues. However, ensuring efficiency and preventing accidents present global challenges. Based on the hypothesis that a simple personality assessment could help address these challenges, the present study aimed to identify genetic markers associated with personality. Eight genes were selected from 18 personality-related candidate genes that are orthologs of human personality genes, and their association with personality was verified based on actual behavior. A total of 169 Thoroughbred horses were assessed for their tractability (questionnaire concerning tractability in 14 types of situations and 3 types of impressions) during the training process. Personality factors were extracted from the data using principal component analysis and analyzed for their association with single nucleotide variants as non-synonymous substitutions in the target genes. Three genes, CDH13, SLC6A4, and MAOA, demonstrated significant associations based on simple linear regression, marking the identification of these genes for the first time as contributors to temperament in Thoroughbred horses. All these genes, as well as the previously identified HTR1A, are involved in the serotonin neurotransmitter system, suggesting that the tractability of horses may be correlated with their social personality. Assessing the genotypes of these genes before retraining is expected to prevent problems in the development of a racehorse's second career and shorten the training period through individual customization of training methods, thereby improving racehorse welfare.

Do Pedicle Screws That Terminate in the Costovertebral Joint Compromise Proximal Anchor Fixation in a Dual Growing Rod Construct?

INTRODUCTION: Growing rods (GRs) are used to treat early-onset scoliosis (EOS) recalcitrant to bracing and casting. Proximal anchor pullout, a known complication of GR constructs, can result in spinal cord injury if pedicle screw anchors are placed with a lateral-to-medial trajectory. To mitigate this risk, a more straightforward and potentially safer trajectory may result in screws that terminate within the costovertebral joint (CVJ). We asked, how often does CVJ placement occur and does this technique increase the rate of failure in GR constructs? METHODS: We retrospectively reviewed 35 patients with EOS treated with dual GR with >2-year follow-up excluding patients with skeletal dysplasia or history of previous posterior instrumentation. Patient demographics, radiographic parameters, and implant constructs were assessed. RESULTS: Of patients meeting the inclusion criteria, 18/35 (51%) were females with an average age of 7.96 (range: 4.0 to 15.2) years at surgery with a follow-up of 3.7 (range: 2.0 to 7.7) years. Five (14%) patients had idiopathic EOS, 5 (14%) had congenital EOS, 12 (34%) had neuromuscular EOS, 10 (29%) had syndromic scoliosis, and 3 (9%) had another etiology for EOS. Among 195 proximal pedicle screws placed, 19 (10%) terminated within the CVJ, and 13 patients (37%) had at least 1 CVJ screw. Two patients (6%) experienced unilateral proximal pullout. In both patients, the anchors on the affected side included 1 of 2 screws within the CVJ. Both patients had constructs that included 2 screws on the side that pulled out and 3 screws on the side that did not. None of the remaining 17 CVJ screws led to implant failure. CONCLUSION: Pedicle screw placement within the CVJ is common and does not appear to significantly contribute to proximal screw pullout; however, it may contribute to unilateral implant failure in constructs employing only 2 proximal screws, where 1 of those 2 screws terminates within the CVJ. Construct modifications should be considered in this scenario. LEVEL OF EVIDENCE: Level III.

Inverse association between DPP-4 inhibitor use and fracture in older adults: A disproportionality analysis of the FAERS and JADER.

OBJECTIVE: Fractures are significantly associated with increased morbidity and mortality in older individuals; additionally, patients with diabetes mellitus are highly prone to fractures. The aim of the present study was to examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and the risk of fracture in older patients by analyzing data obtained from spontaneous adverse event reporting databases from the United States and Japan. MATERIALS AND METHODS: Data on older patients registered in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the end of 2019 and data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to December 2019 were used. Reporting odds ratio (ROR) and information component (IC) values were used for disproportionality analysis. RESULTS: Significant inverse associations between DPP-4 inhibitor use and fracture were found for DPP-4 inhibitors as a whole (ROR = 0.80; 95% CI = 0.73 - 0.88; IC = -0.31, 95% CI = -0.46 to -0.17); linagliptin (ROR = 0.74; 95% CI = 0.59 - 0.94; IC = -0.42, 95% CI = -0.75 to -0.08); and sitagliptin (ROR = 0.77; 95% CI = 0.68 - 0.88; IC = -0.36, 95% CI = -0.55 to -0.17) in the analyses of FAERS data. Similarly, significant inverse associations were also found for DPP-4 inhibitors as whole (ROR = 0.71; 95% CI = 0.59 to 0.86; IC = -0.46, 95% CI = -0.74 to -0.18); sitagliptin (ROR = 0.70; 95% CI = 0.52 - 0.95; IC = -0.49, 95% CI = -0.93 to -0.05); and vildagliptin (ROR = 0.54; 95% CI = 0.35 - 0.83; IC = -0.85, 95% CI = -1.49 to -0.22) in the analyses of JADER data. CONCLUSION: Our analysis of adverse event databases using different algorithms revealed that DPP-4 inhibitor use was inversely associated with fracture in older patients.

Relationship between body mass index and spinal pathology in community-dwelling older adults.

PURPOSE: To clarify the relationship between body mass index (BMI) and spinal pathologies including spinal sagittal balance, back extensor strength (BES), paraspinal muscle mass, prevalent vertebral fracture, disc degeneration, Modic changes, low back pain, and quality of life (QOL) in community-dwelling older adults. METHODS: This study included 380 participants (age: ≥ 65 years, male/female: 152/228) from the Shiraniwa Study. Multivariate nonlinear regression analysis was used to investigate the relationship between BMI and sagittal vertical axis (SVA), BES, paraspinal muscle mass, visual analog scale (VAS) for low back pain, Oswestry Disability Index (ODI), and EuroQoL-5 Dimension (EQ5D) score after adjusting for sex, age, Hospital Anxiety and Depression Scale score, and Charlson Comorbidity Index. In addition, multiple logistic regression analysis was used to investigate the association between BMI and prevalent vertebral fracture, disc degeneration, and Modic changes. RESULTS: BMI was significantly correlated with SVA, BES, paraspinal muscle mass, VAS, ODI, and EQ5D score. The increase in BMI was associated with the deterioration of all outcomes, which accelerated when the BMI increased from approximately 22-23 kg/m2. Moreover, overweight/obesity was significantly correlated with disc degeneration and Modic changes. CONCLUSION: Increased BMI is significantly associated with spinal pathologies such as SVA, BES, paraspinal muscle mass, VAS, QOL, disc degeneration, and Modic changes. The findings suggest that measures for controlling overweight and obesity among older adults can play an important role in the prevention and treatment of spinal pathologies.

Development of locomotive syndrome in elderly population after COVID-19 outbreak: A population-based cross-sectional study with over 12,000 participants.

BACKGROUND: Restrictions during the coronavirus disease 2019 (COVID-19) pandemic have decreased physical activity levels, which may result in locomotive syndrome. This study evaluated the change in locomotive syndrome prevalence and associated risk factors among an elderly population before and after a coronavirus outbreak. METHODS: This written self-administered cross-sectional survey was conducted in conjunction with the coronavirus disease vaccination program in Habikino City, Japan. Participants who were aged ≥65 years completed the five-question Geriatric Locomotive Function Scale before and during the pandemic. The diagnosis of locomotive syndrome and its stage was based on the Geriatric Locomotive Function Scale score: stage 1 (2-3 points), 2 (4-5 points), and 3 (≥6 points). Data on lifestyle changes, including regular exercise, during the pandemic were collected. RESULTS: This study included 12,197 participants (36.7% of the city's total elderly residents). The prevalence of locomotive syndrome increased from 41.3% to 47.1% after the outbreak. In total, 765 (6.3% of overall population) and 295 (9.5% of the participants who had stages 1-2 before the pandemic) participants developed locomotive syndrome and stage 3 locomotive syndrome, respectively. The multivariate logistic regression analysis indicated that a decrease in exercise was significantly associated with the onset of locomotive syndrome (all stages) (odds ratio = 2.5, p < 0.001) and locomotive syndrome stage 3 (odds ratio = 2.6, p < 0.001). CONCLUSIONS: Extrapolation of the study's findings to the entire population of Japan suggests that approximately 2 million elderly individuals might develop locomotive syndrome after the coronavirus outbreak. Additionally, 10% of the participants with mild-moderate locomotive syndrome before the pandemic may develop severe locomotive syndrome after the outbreak. The greatest risk factor for new-onset or worsening locomotive syndrome was a decrease in daily exercise. Thus, there is an urgent need for adequate exercise guidelines during the coronavirus pandemic, especially for the elderly population.

Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (cSRS) as treatment for brain metastasis that recurred locally after initial radiosurgery (BMRS): a multi-institutional experience.

INTRODUCTION: The optimal treatment paradigm for brain metastasis that recurs locally after initial radiosurgery remains an area of active investigation. Here, we report outcomes for patients with BMRS treated with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy, LITT) followed by consolidation radiosurgery. METHODS: Clinical outcomes of 20 patients with 21 histologically confirmed BMRS treated with SLA followed by consolidation SRS and > 6 months follow-up were collected retrospectively across three participating institutions. RESULTS: Consolidation SRS (5 Gy × 5 or 6 Gy × 5) was carried out 16-73 days (median of 26 days) post-SLA in patients with BMRS. There were no new neurological deficits after SLA/cSRS. While 3/21 (14.3%) patients suffered temporary Karnofsky Performance Score (KPS) decline after SLA, no KPS decline was observed after cSRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of cSRS (severe headache that resolved with steroid therapy (n = 1) and new onset seizure (n = 1)). With a median follow-up of 228 days (range: 178-1367 days), the local control rate at 6 and 12 months (LC6, LC12) was 100%. All showed diminished FLAIR volume surrounding the SLA/cSRS treated BMRS at the six-month follow-up; none of the patients required steroid for symptoms attributable to these BMRS. These results compare favorably to the available literature for repeat SRS or SLA-only treatment of BMRS. CONCLUSIONS: This multi-institutional experience supports further investigations of SLA/cSRS as a treatment strategy for BMRS.

Incidence of and risk factors for spondylolisthesis, scoliosis, and vertebral fracture in rheumatoid arthritis.

INTRODUCTION: Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study. MATERIALS AND METHODS: The study cohort comprised 110 patients with RA from the 'analysis of factors for RA spinal disorders (AFFORD)' study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey. RESULTS: The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio [aOR] 4.81, p = 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87, p = 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without. CONCLUSION: The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.

Effect of Concomitant Drug Use on the Onset and Exacerbation of Diabetes Mellitus in Everolimus-Treated Cancer.

PURPOSE: Everolimus-induced diabetes mellitus (DM) outcomes include everolimus-resistant tumors and poor hyperglycemia outcomes, which lead to various other negative clinical outcomes. This study aimed to evaluate the effect of associations between concomitant drug treatment and time to DM event occurrence (onset or exacerbation) on the outcomes of everolimus-induced DM in patients with cancer. METHODS: Data from the Japanese Adverse Drug Event Report database (JADER) were used, and patient drug use, time of DM event occurrence, and DM outcomes were determined from patient records. Associations between concomitant drug groups with everolimus and DM event occurrence were then evaluated for patients with both good and poor DM outcomes. RESULTS: Top ten groups used concomitantly were drugs for the treatment of hypertension (HT), controlled DM, constipation, hypothyroidism, kidney disease, insomnia, hyperlipidemia, hyperuricemia, anemia, and gastritis. Among them, only HT, controlled DM, and hyperlipidemia were associated with DM event occurrence. These three drug groups were examined by the outcome of everolimus concomitant usage and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes (p = 0.015) among patients without a concomitant drug for DM. Each of these three drug groups was analyzed on patients who were concomitantly administered with one of each drug group with everolimus and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes in patients who received concomitant HT drugs (p = 0.006). Moreover, among the four HT drug categories, calcium channel blockers were significantly associated with poor outcomes (odds ratio, 2.18 [1.09-4.34], p = 0.028). CONCLUSION: To prevent everolimus-induced poor DM outcomes, early DM detection and treatment are necessary, and the effect of the concomitant drug should be considered before initiating everolimus treatment.

Association of gynecomastia with antidiabetic medications in older adults: Data mining from different national pharmacovigilance databases.

OBJECTIVE: Gynecomastia is a benign proliferation of the glandular breast tissue in men and is generally caused by a decrease in androgen and an increase in estrogen. Diabetes has been reported to be a risk factor for lowering androgen levels. Moreover, lowered androgen levels are more common in older men. In the present study, we aimed to evaluate the signals for gynecomastia in older men on antidiabetic medications. MATERIALS AND METHODS: A disproportionality analysis was performed to detect the signals for antidiabetic drug-associated gynecomastia in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER), using the reporting odds ratio (ROR) and information component (IC). RESULTS: Among 8 classes of medications for diabetes, a signal was detected only for dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR: 1.90, 95% confidence interval (CI): 1.27 - 2.83; IC: 0.84, 95% CI: 0.26 - 1.42) in the FAERS. Regarding individual drugs, ROR and IC signals were detected for sitagliptin (ROR: 2.37, 95% CI: 1.48 - 3.79; IC: 1.12, 95% CI: 0.44 - 1.79) and vildagliptin (ROR: 3.34, 95% CI: 1.39 - 8.08; IC: 1.26, 95% CI: 0.07 - 2.44) in the FAERS and only for sitagliptin (ROR: 4.84, 95% CI: 1.92 - 12.2; IC: 1.48, 95% CI: 0.24 - 2.73) in the JADER. CONCLUSION: This study showed an association between DPP-4 inhibitor use and gynecomastia in older men with diabetes. Further pharmacoepidemiological studies are warranted to verify this finding.

Decreased muscle mass and strength affected spinal sagittal malalignment.

PURPOSE: Correction surgeries for spinal malalignment showed good clinical outcomes; however, there were concerns including increased invasiveness, complications, and impact on medico-economics. Ideally, an early intervention is needed. To better understand the patho-mechanism and natural course of spinal alignment, the effect of factors such as muscle mass and strength on spinal sagittal imbalance were determined in a multicenter cross-sectional study. METHODS: After excluding metal implant recipients, 1823 of 2551 patients (mean age: 69.2 ± 13.8 years; men 768, women 1055) were enrolled. Age, sex, past medical history (Charlson comorbidity index), body mass index (BMI), grip strength (GS), and trunk muscle mass (TM) were reviewed. Spinal sagittal imbalance was determined by the SRS-Schwab classification. Multiple comparison analysis among four groups (Normal, Mild, Moderate, Severe) and multinomial logistic regression analysis were performed. RESULTS: On multiple comparison analysis, with progressing spinal malalignment, age in both sexes tended to be higher; further, TM in women and GS in both sexes tended to be low. On multinomial logistic regression analysis, age and BMI were positively associated with spinal sagittal malalignment in Mild, Moderate, and Severe groups. TM in Moderate and Severe groups and GS in the Moderate group were negatively associated with spinal sagittal malalignment. CONCLUSION: Aging, obesity, low TM, and low GS are potential risk factors for spinal sagittal malalignment. Especially, low TM and low GS are potentially associated with more progressed spinal sagittal malalignment. Thus, early intervention for muscles, such as exercise therapy, is needed, while the spinal sagittal alignment is normal or mildly affected.

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis.

BACKGROUND: Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures. METHODS: We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-ß1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-ß1-induced myofibroblast differentiation and fibrosis. RESULTS: Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-ß1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-ß1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells. CONCLUSION: FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-ß1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.

The health-related quality of life of patients with musculoskeletal disorders after the COVID-19 pandemic.

PURPOSE: To verify changes in the health-related quality of life (HRQOL) of patients with musculoskeletal disorders after the coronavirus disease 2019 (COVID-19) pandemic and to assess the relationship between the patients' change in several activities of daily living and in the HRQOL to discover factors related to the deterioration in HRQOL. METHODS: A multi-centre cross-sectional questionnaire survey was administered between November 1, 2020, and December 31, 2020, in Japan. The participants included those who visited the orthopaedics clinic within the survey period and had experienced the first and second waves of COVID-19 in Japan and the first stay-at-home order issued by the government. Patients' HRQOL at the two different time points (pre-outbreak and post-second wave of COVID-19) was assessed with the EuroQoL-5 dimensions 5-level (EQ-5D). RESULTS: The survey was completed by 1254 patients (average age: 52.5 ± 21.9 years; 644 women). Among them, 431 patients (34.3%) reported a decrease in the EQ-5D index after the pandemic. The largest decrease was in the pain domain followed by the mobility domain. Multivariate logistic regression analysis revealed that the patients with decreased regular exercise habits were significantly related to deterioration in HRQOL compared with those with stable regular exercise (adjusted odds ratio = 1.76, p < 0.001) independently from age, sex, and change of symptoms. CONCLUSIONS: Up to 35% of patients with musculoskeletal disorders reported deterioration of HRQOL after the COVID-19 pandemic. Pain and mobility rather than anxiety were the two leading factors of the HRQOL decrease. The decrease in regular exercise was related to the HRQOL decrease.

Impact of Door-to-Balloon Time Reduction Depending on the Killip Classification in Patients with ST-Segment Elevation Myocardial Infarction Transported by Emergency Medical Services.

The coronavirus disease 2019 pandemic occurred in several countries, making the conventional medical system difficult to maintain. Recent recommendations aim to prevent nosocomial infections and infections among health care workers. Therefore, establishing a cardiovascular medical system under an emergency for patients with ST-segment elevation myocardial infarction (STEMI) is desired. This study aimed to determine the relationship between prognosis and door-to-balloon time (DBT) shortening based on the severity on arrival.This retrospective, multi-center, observational study included 1,127 consecutive patients with STEMI. These patients were transported by emergency medical services and underwent primary percutaneous coronary intervention. Patients were stratified according to the Killip classification: Killip 1 (n = 738) and Killip ≥ 2 (n = 389) groups.Patients in the Killip ≥ 2 group were older, with more females, and more severity on arrival than those in the Killip 1 group. The 30-day mortality rate in the Killip 1 and Killip ≥ 2 groups was 2.2% and 18.0%, respectively. The Killip ≥ 2 group had a significant difference in the 30-day mortality between patients with DBT ≤ 90 minutes and those with DBT > 90 minutes; however, this did not occur in the Killip 1 group. Furthermore, multivariate analysis revealed that DBT ≤ 90 minutes was not a significant predictive factor in the Killip 1 group; however, it was an independent predictive factor in the Killip ≥ 2 group.DBT shortening affected the 30-day mortality in STEMI patients with Killip ≥ 2, although not those with Killip 1.

Risk factors for low back pain increase in rheumatoid arthritis: Analysis of a 7-year follow-up study.

OBJECTIVE: Several studies have demonstrated that low back pain (LBP) is related to disease activity in patients with rheumatoid arthritis (RA). However, there is no longitudinal research. This study aimed to determine the impacts and risk factors for LBP increase in RA in a longitudinal cohort study. METHODS: The study evaluated 113 patients with RA who completed the secondary survey. LBP increase was defined as ≥1 standard deviation of mean change in visual analogue scale (VAS) between the baseline and secondary surveys. The impacts of LBP increase on quality of life (QOL) and psychological status were evaluated. Risk factors were assessed among patient demographic characteristics and radiological changes. RESULTS: Mean change in VAS for LBP was -0.8 ± 30.4 mm during a mean 7-year follow-up. LBP increase was defined as ≥30-mm increase in VAS for LBP. Patients with LBP increase had significantly lower QOL and worse mental status than patients without it. Poor control of RA was identified as an independent risk factor for LBP increase (odds ratio, 9.82, p = .001). CONCLUSION: Patients with poor control of RA were likely to experience LBP increase in the long term. Control of RA disease activity is important for control of LBP, QOL, and mental status.

Dogs and cats prioritize human action: choosing a now-empty instead of a still-baited container.

Dogs and cats are sensitive to human social signals such as pointing, gazing and facial expressions. Previous studies have demonstrated that dogs show over-reliance on human actions in the presence of conflicting physical cues. However, it is still unclear whether this tendency is specific to dogs, or shared with other domesticated animals. Here, we compared the behavior of dogs and cats in a two-choice task after they saw a person taking and pretending to eat food from a baited container. After one experimenter showed the dogs (Experiment 1) or cats (Experiment 2) two opaque containers, each containing a piece of the food, another (the demonstrator) removed food from one container and ate it (Eating condition), or simply picked up the food and returned it to the container (Showing condition). We recorded which container the subjects approached first after the demonstration. Both dogs and cats were less likely to choose the container associated with the human in the Eating than the Showing condition, although choice for this container was above chance in both conditions. In Experiment 3, we confirmed that dogs and cats naturally chose a baited over an empty container. These results suggest that both species' reasoning abilities might be influenced by a bias for prioritizing specific human actions. Although dogs and cats have different domestication histories, their social awareness of humans appears similar, possibly because they both share their environment with humans.

Xerostomia aggravates ligation-induced peri-implantitis: A preclinical in vivo study.

OBJECTIVES: Previous studies have indicated that xerostomia is a critical factor affecting periodontitis; nonetheless, it is controversial whether xerostomia impairs peri-implant tissue. The objective of this experimental study was to evaluate the effect of xerostomia on the peri-implant hard and soft tissues in the rat model. MATERIALS AND METHODS: Implants were placed in bilateral maxillae of male Wistar rats. The animals underwent submandibular and sublingual gland resection on both sides (DRY group) or sham operation (CTR group). Silk ligatures were placed around one side of abutments, which were randomly selected in each animal. The effects of xerostomia were assessed using micro-CT, histological analysis, real-time PCR, and 16S rRNA-based metagenomic analysis. RESULTS: Ligation with silk thread caused bone resorption around implants. Although xerostomia itself did not induce bone resorption, it significantly enhanced silk ligature-mediated bone resorption around implants. Histological analysis and real-time PCR indicated that xerostomia induced inflammation and osteoclastogenesis around implants with silk ligatures. Furthermore, it altered the microbiota of the plaque on the silk thread around implants. CONCLUSION: Xerostomia accelerates mucosal inflammation and osteoclastogenesis, which aggravates bone resorption around implants.

Classification and prognostic factors of residual symptoms after minimally invasive lumbar decompression surgery using a cluster analysis: a 5-year follow-up cohort study.

PURPOSE: Residual symptoms indicating incomplete remission of lower leg numbness or low back pain may occur after spine surgery. The purpose was to elucidate the pattern of residual symptoms 5 years after minimally invasive lumbar decompression surgery using a cluster analysis. METHODS: The study comprised 193 patients with lumbar spinal stenosis (LSS) (108 men, 85 women) ranging in age from 40 to 86 years (mean, 67.9 years). Each patient underwent 5-year follow-up. The Japanese Orthopedic Association score and visual analog scale scores for low back pain, leg pain, and leg numbness at 5 years were entered into the cluster analysis to characterize postoperative residual symptoms. Other clinical data were analyzed to detect the factors significantly related to each cluster. RESULTS: The analysis yielded four clusters representing different patterns of residual symptoms. Patients in cluster 1 (57.0%) were substantially improved and had few residual symptoms of LSS. Patients in cluster 2 (11.4%) were poorly improved and had major residual symptoms. Patients in cluster 3 (17.6%) were greatly improved but had mild residual low back pain. Patients in cluster 4 (14.0%) were improved but had severe residual leg numbness. Prognostic factors of cluster 2 were a short maximum walking distance, motor weakness, resting lower leg numbness, cofounding scoliosis, and high sagittal vertical axis. CONCLUSIONS: This is the first study to identify specific patterns of residual symptoms of LSS after decompression surgery. Our results will contribute to acquisition of preoperative informed consent and identification of patients with the best chance of postoperative improvement.

Predictors of dropout from cohort study due to deterioration in health status, with focus on sarcopenia, locomotive syndrome, and frailty: From the Shiraniwa Elderly Cohort (Shiraniwa) study.

BACKGROUND: Conditions of the elderly like sarcopenia, locomotive syndrome, and frailty have been attracting attention recently. However, the relationship of these 3 conditions and the difference in the magnitude of influence each has on deterioration in health status remain unclear. The purpose of this study was to investigate the prevalence and relationship of sarcopenia, locomotive syndrome, and frailty, and to clarify their influence on the dropout from cohort study due to deterioration in health status. METHODS: The 1st survey of the Shiraniwa Elderly Cohort (Shiraniwa) study was conducted in 2016. We examined 409 participants (aged ≥ 65 years; 164 males, 245 females) and assessed sarcopenia, locomotive syndrome, and frailty. Those who could not attend the 2nd survey (2017) due to deterioration in health status were defined as the Dropout group. We investigated the predictors of Dropout using multiple logistic regression analysis. RESULTS: The prevalence of sarcopenia, locomotive syndrome stage 2, and frailty were 4.4%, 40.1%, and 14.2%, respectively; 89.7% of participants with frailty were also diagnosed with locomotive syndrome stage 2. From the results of the 2nd survey, 46 people were classified into the Dropout group. Independent predictors of the Dropout were locomotive syndrome stage 2 (adjusted odds ratio [OR]: 2.42, 95% confidence interval [CI]: 1.11-5.31) and frailty (adjusted OR: 3.37, 95%CI: 1.56-7.30). CONCLUSIONS: Locomotive syndrome stage 2 was the most common condition in the elderly, and most people with frailty also had locomotive syndrome stage 2. Locomotive syndrome stage 2 and frailty independently influenced the dropout from cohort study due to deterioration in health status. These results suggest that screening for locomotive syndrome is useful for early detection of the elderly with a risk of deterioration in health status, and screening for frailty may contribute to detecting the elderly with higher risk of deterioration in health status.

Fatal Embolic ST-Elevation Myocardial Infarction Secondary to Healed-Phase Mitral Valve Infective Endocarditis.

Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.