Imeglimin modulates mitochondria biology and facilitates mitokine secretion in 3T3-L1 adipocytes.

AIMS: Imeglimin, a novel antidiabetic drug, has recently been reported to affect pancreatic ß-cells and hepatocytes. Adipose tissue plays a crucial role in systemic metabolism. However, its effect on adipocytes remains unexplored. Herein, we investigated the effects of imeglimin on adipocytes, particularly in the mitochondria. MAIN METHODS: The 3T3-L1 adipocytes were treated with imeglimin. Mitochondrial respiratory complex I activity and NAD+, NADH, and AMP levels were measured. Protein expression levels were determined by western blotting, mitochondrial DNA and mRNA expression levels were determined using quantitative polymerase chain reaction, and secreted adipocytokine and mitokine levels were determined using adipokine array and enzyme-linked immunosorbent assay. KEY FINDINGS: Imeglimin inhibited complex I activity, decreased the NAD+/NADH ratio, and increased AMP levels, which were associated with the enhanced phosphorylation of AMP-activated protein kinase. In addition, imeglimin increased the mitochondrial DNA content and levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-γ coactivator 1-α mRNA, which were abolished by Ly294002, a phosphoinositide 3-kinase inhibitor. Furthermore, imeglimin facilitated the expression levels of markers of the mitochondrial unfolded protein response, and the gene expression and secretion of two mitokines, fibroblast growth factor 21 and growth differentiation factor 15. The production of both mitokines was transcriptionally regulated and abolished by phosphoinositide 3-kinase and Akt inhibitors. SIGNIFICANCE: Imeglimin modulates mitochondrial biology in adipocytes and may exert a mitohormetic effect through mitokine secretion.

Serum bta-miRNA-375 as a potential biomarker for the early diagnosis of enzootic bovine leukosis.

To identify a biomarker for the early diagnosis of enzootic bovine leukosis (EBL) caused by bovine leukemia virus (BLV), we investigated the expression of a microRNA, bta-miR-375, in cattle serum. Using quantitative reverse-transcriptase PCR analysis, we measured bta-miR-375 levels in 27 samples from cattle with EBL (EBL cattle), 45 samples from animals infected with BLV but showing no clinical signs (NS cattle), and 30 samples from cattle uninfected with BLV (BLV negative cattle). In this study, we also compared the kinetics of bta-miR-375 with those of the conventional biomarkers of proviral load (PVL), lactate dehydrogenase (LDH), and thymidine kinase (TK) from the no-clinical-sign phase until EBL onset in three BLV-infected Japanese black (JB) cattle. Bta-miR-375 expression was higher in NS cattle than in BLV negative cattle (P < 0.05) and greater in EBL cattle than in BLV negative and NS cattle (P < 0.0001 for both comparisons). Receiver operating characteristic curves demonstrated that bta-miR-375 levels distinguished EBL cattle from NS cattle with high sensitivity and specificity. In NS cattle, bta-miR-375 expression was increased as early as at 2 months before EBL onset-earlier than the expression of PVL, TK, or LDH isoenzymes 2 and 3. These results suggest that serum miR-375 is a promising biomarker for the early diagnosis of EBL.

Conditional deletion of IκBζ in hematopoietic cells promotes functional recovery after spinal cord injury in mice.

BACKGROUND: Transcription factor protein IκBζ (encoded by the Nfkbiz gene) regulates nuclear factor-κB (NF-κB) and is involved in the pathophysiology of various inflammatory diseases. However, the role of IκBζ in secondary damage following spinal cord injury (SCI) remains to be determined. Here, we investigated the effect of IκBζ expressed in hematopoietic cells on the progression of secondary damage and functional recovery after SCI. METHODS: We used conditional IκBζ-knockout mice (Mx1-Cre;Nfkbizfl/f) to examine the role of IκBζ in hematopoietic cells after SCI. Contusion SCI was induced using a force of 60 kdyn. The recovery of locomotor performance was evaluated using the nine-point Basso Mouse Scale (BMS) until 42 days post-injury. Expression patterns of inflammatory cytokines and chemokines were examined by quantitative real-time PCR or proteome array analysis. Bone marrow transplantation (BMT) was performed to eliminate the effect of IκBζ deletion in non-hematopoietic cells. RESULTS: Mx1-Cre;Nfkbizfl/fl mice had significantly improved locomotor function compared with wild-type (WT) mice. The mRNA expression of Nfkbiz in WT mice peaked at 12 h after SCI and then decreased slowly in both the spinal cord and white blood cells. In situ hybridization showed that Nfkbiz mRNA was localized in cell nuclei, including macrophage-like cells, in the injured spinal cord of WT mice at 1 day after SCI. Compared with WT mice, Mx1-Cre;Nfkbizfl/fl mice had significantly increased mRNA expressions of interleukin (Il)-4 and Il-10 in the injured spinal cord. In addition, Mx1-Cre;Nfkbizfl/fl mice had significantly higher protein levels of granulocyte-macrophage colony-stimulating factor and C-C motif chemokine 11 compared with WT mice. BMT from Mx1-Cre;Nfkbizfl/fl mice into WT mice improved functional recovery after SCI compared with control mice (WT cells into WT mice). CONCLUSIONS: IκBζ deletion in hematopoietic cells improved functional recovery after SCI, possibly by shifting the inflammatory balance towards anti-inflammatory and pro-regenerative directions.

Cerebrospinal Fluid Lysophosphatidylcholine Species for Distinguishing Narrowing of the Lumbar Spine.

BACKGROUND: Reoperation, sometimes multiple, is common with progressively worse outcomes in patients with degenerative lumbar spine diseases. Lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acid, in the cerebrospinal fluid (CSF) is a possible biomarker for neuropathic pain and discriminating neuropathic pain caused by lumbar spinal canal stenosis (LSCS) from other etiologies. This study aimed to explore this possible use of LPC species in the CSF. METHODS: Patients with LSCS (n = 137) and persistent spinal pain syndrome (n = 22) were subjected in this multi-site observational study. The CSF was collected by lumbar puncture. Using liquid chromatography-tandem mass spectrometry, we measured 6 LPC species, (16:0), (18:0), (18:1), (18:2), (20:4), and (22:6), in the CSF. We compared the LPC values between the groups and determined the cutoff levels that could efficiently discriminate the groups with high accuracy. RESULTS: The levels of all measured LPC species were significantly higher in the LSCS group than the persistent spinal pain syndrome group. Four LPC species demonstrated more than 0.80 area under the curve obtained from the receiver operating characteristic curve analysis. Although the specificity of cutoff levels for the 6 LPC species was low to moderate, their sensitivity was consistently high. CONCLUSIONS: The existing diagnostic protocols combining physical examinations and morphological imaging studies for lumbar spinal pain have limited sensitivity. Measuring LPC species in the CSF is a promising objective laboratory test and could be suitable for detecting the presence of lumbar spinal stenosis and can help indications for surgery.

Effectiveness of a two-stage posterior-anterior-posterior surgery using subcutaneously preserved autologous bone grafts for adult spinal deformity: a retrospective observational study.

BACKGROUND: To achieve optimal correction of rigid kyphoscoliosis, we developed a novel two-stage posterior-anterior-posterior (PAP) surgery using subcutaneously preserved autologous bone grafts. This study aimed to investigate the effectiveness of two-stage PAP surgery versus single-stage anterior-posterior (AP) surgery. METHODS: This was a retrospective analysis of patients undergoing combined anterior-posterior long-level fusion for adult spinal deformity (ASD) with a minimum 2-year follow-up. The indications for two-stage PAP surgery were rigid thoracolumbar deformity associated with hypertrophic facet arthritis and/or a large pelvic incidence-lumbar lordosis mismatch of > 25°. In the first stage of PAP surgery, pedicle screw insertion and multilevel Ponte osteotomies were performed. The resected local bone was embedded under sutured fascia. One week later, the embedded bone was retrieved in the right lateral position and used as an autograft for lateral lumbar interbody fusion. Final deformity correction was performed in the prone position. RESULTS: From January 2018 to April 2021, 12 and 16 patients with ASD underwent two-stage PAP surgery (PAP group) and single-stage AP surgery (AP group), respectively. Although PAP surgery was associated with a significantly longer operation time, the total blood loss volume was significantly less in the PAP group than the AP group. Compared with the AP group, the PAP group showed significantly larger postoperative changes in radiological parameters in the sagittal and coronal planes. The overall complication rate did not differ significantly between the two groups. CONCLUSION: Two-stage PAP surgery provided effective correction of rigid kyphoscoliosis without increasing blood loss and postoperative complication rates.

A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists.

STUDY OBJECTIVES: Although novel hypnotics have recently emerged, there are currently no data comparing the clinical potency of benzodiazepine receptor agonists (BZRAs) and novel hypnotics, or the effectiveness of different methods of switching between them. This study examined how novel hypnotics might help reduce BZRA use in real-world practice. METHODS: 289 patients with psychiatric disorders who took BZRAs for over 1 year before switching to either of 2 dual-orexin receptor antagonists (DORAs; suvorexant [SUV] or lemborexant [LEM]) or a melatonin receptor agonist (ramelteon [RMT]) were enrolled. We collected data on BZRAs at baseline and 3 months after commencement of SUV/LEM/RMT. RESULTS: Significant reductions in BZRAs were observed for all 3 agents: -4.10, -2.80, and -1.65 mg in diazepam-equivalent doses in the SUV, LEM, and RMT groups, respectively. Dose reduction was significantly greater in the DORA than the RMT group (F = 15.053, P < .001). Within the DORA group, dose reduction was significantly greater in patients taking SUV than those taking LEM (F = 4.337, P = .043). The switching success rate did not differ among the switching methods for any of the hypnotics. CONCLUSIONS: The reduction rate of BZRAs achieved by the switch fell into their equivalent-potency range estimated from clinical trials. The results suggest that DORAs can replace approximately 1 tablet of a BZRA. The difference in dose reduction between DORAs and RMT reflected the greater sleeping potency of the DORAs, whereas that between SUV and LEM might have reflected patient backgrounds: patients taking LEM may have been more strongly dependent on BZRAs. CITATION: Tachibana M, Kanahara N, Oda Y, Hasegawa T, Kimura A, Iyo M. A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists. J Clin Sleep Med. 2024;20(4):603-613.

PTBP2 binds to a testis-specific long noncoding RNA, Tesra, and activates transcription of the Prss42/Tessp-2 gene.

Long noncoding RNAs (lncRNAs) have recently been proved to be functional in the testis. Tesra, a testis-specific lncRNA, was suggested to activate the transcription of Prss42/Tessp-2, a gene that is involved in meiotic progression, in mouse spermatocytes. To reveal the molecular mechanism underlying the activation, we searched for Tesra-binding proteins by a Ribotrap assay followed by LC-MS/MS analysis and identified polypyrimidine tract binding protein 2 (PTBP2) as a candidate. Analysis of public RNA-seq data and our qRT-PCR results indicated that Ptbp2 mRNA showed an expression pattern similar to the expression patterns of Tesra and Prss42/Tessp-2 during testis development. Moreover, PTBP2 was found to be associated with Tesra in testicular germ cells by RNA immunoprecipitation. To evaluate the effect of PTBP2 on the Prss42/Tessp-2 promoter, we established an in vitro reporter gene assay system in which Tesra expression could be induced by the Tet-on system and thereby Prss42/Tessp-2 promoter activity could be increased. In this system, the Prss42/Tessp-2 promoter activity was significantly decreased by the knockdown of PTBP2. These results suggest that PTBP2 contributes to Prss42/Tessp-2 transcriptional activation by Tesra in spermatocytes. The finding provides a precious example of a molecular mechanism of testis lncRNA functioning in spermatogenesis.

Corticobasal syndrome mimicking Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET.

BACKGROUND: Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy. CASE PRESENTATION: A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months. CONCLUSION: We hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

Geospatial intelligence system for evaluating the work environment and physical load of factory workers.

This study aimed to assess the effectiveness of methods for evaluating the environmental and physical loads on workers in manufacturing plants, considering their locations. Participants were employees of DENSO CORPORATION's manufacturing facilities, and environmental sensors (for temperature and humidity) and BLE beacons were installed to cover the work area. Questionnaires were completed by the participants twice to assess their thermal comfort and fatigue in the work environment. The results showed that a regression prediction model with an adjusted R-squared of 0.418 for fixed-point temperature and 0.495 for perceived temperature was developed for thermal comfort. No linear relationship was found between environmental factors and fatigue, and a decision tree analysis was conducted. Relative humidity and activity level, along with temperature, were selected as predictor variables. The findings suggest that it is possible to estimate the work environment and workload without adding additional measurement-related burdens or challenges. This highlights the usefulness of the proposed method, which takes into account the environmental distribution throughout the work area rather than relying solely on conventional fixed-point observation data, for assessing workers' exposure to the environment and preventing occupational accidents.Clinical Relevance- The proposed approach, combining indoor localization with environmental status, can estimate the condition of workers and is expected to be a good solution for preventing occupational accidents and enhancing workers' health.

Extracellular high molecular weight α-synuclein oligomers induce cell death by disrupting the plasma membrane.

α-Synuclein (αS), the causative protein of Parkinson's disease and other α-synucleinopathies, aggregates from a low molecular weight form (LMW-αS) to a high molecular weight αS oligomer (HMW-αSo). Aggregated αS accumulates intracellularly, induces intrinsic apoptosis, is released extracellularly, and appears to propagate disease through prion-like spreading. Whether extracellular αS aggregates are cytotoxic, damage cell wall, or induce cell death is unclear. We investigated cytotoxicity and cell death caused by HMW-αSo or LMW-αS. Extracellular HMW-αSo was more cytotoxic than LMW-αS and was a crucial factor for inducing plasma membrane damage and cell death. HMW-αSo induced reactive oxygen species production and phospholipid peroxidation in the membrane, thereby impairing calcium homeostasis and disrupting plasma membrane integrity. HMW-αSo also induced extrinsic apoptosis and cell death by activating acidic sphingomyelinase. Thus, as extracellular HMW-αSo causes neuronal injury and death via cellular transmission and direct plasma membrane damage, we propose an additional disease progression pathway for α-synucleinopathies.

Exploring Whether Weight-Related Cues Affect Food Intake in Older Adults with Dementia.

Purpose: Past research has shown that exposure to the image of a slim person reduces food consumption among young adults. However, it remains unknown whether this paradigm could be adapted and applied to increase food intake among older adults with dementia by exposing them to the image of a higher-weight person to mitigate weight loss and malnutrition. The present study explored whether weight-related visual cues affect the amount of food consumed by older adults with dementia. Participants and Methods: In the experiment, twenty-one elderly people with dementia living in a nursing home were visually exposed to one of four conditions (a cartoon image of a normal-weight chef, a higher-weight chef, a flower or no image) during real-life daily lunch situations over the course of four weeks, during which each condition was presented for one week. Results: Results demonstrate that participants finished their meals more frequently when they were exposed to the image of the higher-weight chef than when they were not exposed to any images. Conclusion: These results suggest that exposure to a cartoon chef character representing a stereotyped social group related to body weight activates the stereotype and increases stereotype-consistent behavior in older adults with dementia. The present findings will contribute to understanding the effect of visual information on eating behavior and to designing eating environments which facilitate sufficient nutrition intake among older adults with dementia.

Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.

PURPOSE: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. METHODS: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. RESULTS: Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). CONCLUSIONS: From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.

A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen.

Tissue kallikrein 1 (Klk1) is a serine protease that degrades several proteins including insulin-like growth factor binding protein-3 and extracellular matrix molecules. Klk1 mRNA expression in the mouse uterus was increased by estradiol-17ß (E2). The present study aimed to clarify the regulatory mechanism for Klk1 expression by estrogen. The promoter analysis of the 5'-flanking region of Klk1 showed that the minimal promoter of Klk1 existed in the -136/+24 region, and the estrogen-responsive region in the -433/-136 region. Tamoxifen increased Klk1 mRNA expression and the promoter activity, suggesting the involvement of AP-1 sites. Site-directed mutagenesis for the putative AP-1 sites in the -433/-136 region showed that the two putative AP-1 sites were involved in the regulation of Klk1 expression. Binding of estrogen receptor α (ERα) to the -433/-136 region was revealed by Chip assay. These results indicated that ERα bound the two putative AP-1 sites and transactivated Klk1 in the mouse uterus.

Preoperative Symptom Duration Influences Neurological Recovery and Patient-Reported Outcome Measures After Surgical Treatment of Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: To investigate the effect of preoperative symptom duration on neurological recovery for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The optimal timing to perform surgery in the setting of cervical OPLL remains unknown. It is important to know the influence of symptom duration on postoperative outcomes to facilitate discussions regarding the timing of surgery. PATIENTS AND METHODS: The study included 395 patients (291 men and 104 women; mean age, 63.7 ± 11.4 yr): 204 were treated with laminoplasty, 90 with posterior decompression and fusion, 85 with anterior decompression and fusion, and 16 with other procedures. The Japanese Orthopedic Association (JOA) score and patient-reported outcomes of the JOA Cervical Myelopathy Evaluation Questionnaire were used to assess clinical outcomes preoperatively and 2 years after surgery. Logistic regression analysis was used to identify factors associated with the achievement of minimum clinically important difference (MCID) after surgery. RESULTS: The recovery rate was significantly lower in the group with symptom duration of ≥5 years compared with the groups with durations of <0.5 years, 0.5 to 1 year, and 1 to 2 years. Improvement of JOA Cervical Myelopathy Evaluation Questionnaire in the upper extremity function score ( P < 0.001), lower extremity function ( P = 0.039), quality of life ( P = 0.053), and bladder function ( P = 0.034) were all decreased when the symptom duration exceeded 2 years. Duration of symptoms ( P = 0.001), age ( P < 0.001), and body mass index ( P < 0.001) were significantly associated with the achievement of MCID. The cutoff value we established for symptom duration was 23 months (area under the curve, 0.616; sensitivity, 67.4%; specificity, 53.5%). CONCLUSIONS: Symptom duration had a significant impact on neurological recovery and patient-reported outcome measures in this series of patients undergoing surgery for cervical OPLL. Patients with symptom duration exceeding 23 months may be at greater risk of failing to achieve MCID after surgery. LEVEL OF EVIDENCE: 3.

Factors Associated With Loss of Cervical Lordosis After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: Data From a Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: The objective of this study was to investigate the incidence of loss of cervical lordosis after laminoplasty for cervical ossification of the posterior longitudinal ligament (OPLL). We also sought to determine associated risk factors and the relationship with patient-reported outcomes. SUMMARY OF BACKGROUND DATA: Loss of cervical lordosis is a sequelae often observed after laminoplasty, which may adversely impact surgical outcomes. Cervical kyphosis, especially in OPLL, is associated with reoperation, but risk factors and relationship to postoperative outcomes remain understudied at this time. MATERIALS AND METHODS: This study was conducted by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. We included 165 patients who underwent laminoplasty and completed Japanese Orthopaedic Association (JOA) score or Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaires (JOACMEQ), as well as Visual Analog Scales (VAS) for pain, with imaging. The participants were divided into two groups: those with loss of cervical lordosis of >10° or 20° after surgery and those without loss of cervical lordosis. A paired t test was applied to evaluate the association between changes in cervical spinal angles, range of motion, and cervical JOA and VAS scores before and at 2 years postoperatively. Mann-Whitney U test was used for JOACMEQ. RESULTS: Postoperative loss of cervical lordosis >10° and >20° was observed in 32 (19.4%) and 7 (4.2%), respectively. JOA, JOACMEQ, and VAS scores were not significantly different between those with, and without, loss of cervical lordosis. Preoperative small extension range of motion (eROM) was significantly associated with postoperative loss of cervical lordosis, and the cutoff values of eROM were 7.4° [area under the curve (AUC): 0.76] and 8.2° (AUC: 0.92) for loss of cervical lordosis >10° and >20°, respectively. A large occupation ratio of OPLL was also associated with loss of cervical lordosis, with a cutoff value of 39.9% (AUC: 0.94). Laminoplasty resulted in functional improvement in most patient-reported outcomes; however, neck pain and bladder function tended to become worse postoperatively in cases with postoperative loss of cervical lordosis >20°. CONCLUSIONS: JOA, JOACMEQ, and VAS scores were not significantly different between those with, and without, loss of cervical lordosis. Preoperative small eROM and large OPLL may represent factors associated with loss of cervical lordosis after laminoplasty in patients with OPLL.

Predicted functional analysis of rumen microbiota suggested the underlying mechanisms of the postpartum subacute ruminal acidosis in Holstein cows.

BACKGROUND: The relationships between the postpartum subacute ruminal acidosis (SARA) occurrence and predicted bacterial functions during the periparturient period are still not clear in Holstein cows. OBJECTIVES: The present study was performed to investigate the alterations of rumen fermentation, bacterial community structure, and predicted bacterial functional pathways in Holstein cows. METHODS: Holstein cows were divided into the SARA (n = 6) or non-SARA (n = 4) groups, depending on whether they developed SARA during the first 2 weeks after parturition. Reticulo-ruminal pH was measured continuously during the study period. Reticulo-ruminal fluid samples were collected 3 weeks prepartum, and 2 and 6 weeks postpartum, and blood samples were collected 3 weeks before, 0, 2, 4 and 6 weeks postpartum. RESULTS: The postpartum decline in 7-day mean reticulo-ruminal pH was more severe and longer-lasting in the SARA group compared with the non-SARA group. Changes in predicted functional pathways were identified in the SARA group. A significant upregulation of pathway "PWY-6383" associated with Mycobacteriaceae species was identified at 3 weeks after parturition in the SARA group. Significantly identified pathways involved in denitrification (DENITRIFICATION-PWY and PWY-7084), detoxification of reactive oxygen and nitrogen species (PWY1G-0), and starch degradation (PWY-622) in the SARA group were downregulated. CONCLUSIONS: The postpartum SARA occurrence is likely related to the predicted functions of rumen bacterial community rather than the alterations of rumen fermentation or fluid bacterial community structure. Therefore, our result suggests the underlying mechanisms, namely functional adaptation of bacterial community, causing postpartum SARA in Holstein cows during the periparturient period.

Effects of oral ß-cryptoxanthin administration on the transcriptomes of peripheral neutrophil and liver tissue using microarray analysis in post-weaned Holstein calves.

We investigated the effects of oral administration of ß-cryptoxanthin (ß-CRX), a precursor of vitamin A synthesis, on the transcriptomes of peripheral neutrophils and liver tissue in post-weaned Holstein calves with immature immunity. A single oral administration of ß-CRX (0.2 mg/kg body weight) was performed in eight Holstein calves (4.0 ± 0.8 months of age; 117 ± 10 kg) on Day 0. Peripheral neutrophils (n = 4) and liver tissue (n = 4) were collected on Days 0 and 7. Neutrophils were isolated by density gradient centrifugation and treated with the TRIzol reagent. mRNA expression profiles were examined by microarray and differentially expressed genes were investigated using the Ingenuity Pathway Analysis software. The differentially expressed candidate genes identified in neutrophils (COL3A1, DCN, and CCL2) and liver tissue (ACTA1) were involved in enhanced bacterial killing and maintenance of cellular homoeostasis respectively. The changes in the expression of six of the eight common genes encoding enzymes (ADH5 and SQLE) and transcription regulators (RARRES1, COBLL1, RTKN, and HES1) were in the same direction in neutrophils and liver tissue. ADH5 and SQLE are involved in the maintenance of cellular homoeostasis by increasing the availability of substrates, and RARRES1, COBLL1, RTKN, and HES1 are associated with the suppression of apoptosis and carcinogenesis. An in silico analysis revealed that MYC, which is related to the regulation of cellular differentiation and apoptosis, was the most significant upstream regulator in neutrophils and liver tissue. Transcription regulators such as CDKN2A (cell growth suppressor) and SP1 (cell apoptosis enhancer) were significantly inhibited and activated, respectively, in neutrophils and liver tissue. These results suggest that oral administration of ß-CRX promotes the expression of candidate genes related to bactericidal ability and regulation of cellular processes in peripheral neutrophils and liver cells in response to the immune-enhancing function of ß-CRX in post-weaned Holstein calves.

Handgrip strength is correlated with activities of daily living, balance, and body composition in patients with thoracolumbar compression fracture.

This study assessed the relationship between handgrip strength (HGS) and activities of daily living, balance, walking speed, calf circumference, body muscle, and body composition in elderly patients with thoracolumbar vertebral compression fracture (VCF). A cross-sectional study in a single hospital was performed with elderly patients diagnosed with VCF. After admission, we evaluated HGS, 10-meter walk test (speed), Barthel Index, Berg Balance Scale (BBS), numerical rating scale of body pain, and calf circumference. We examined skeletal muscle mass, skeletal muscle mass index, total body water (TBW), intracellular water, extracellular water (ECW), and phase angle (PhA) in patients with VCF using multi-frequency direct segmental bioelectrical impedance analysis after admission. A total of 112 patients admitted for VCF were enrolled (26 males, 86 females; mean age 83.3 years). The prevalence of sarcopenia according to the 2019 Asian Working Group for Sarcopenia guideline was 61.6%. HGS was significantly correlated with walking speed (P < .001, R = 0.485), Barthel Index (P < .001, R = 0.430), BBS (P < .001, R = 0.511), calf circumference (P < .001, R = 0.491), skeletal muscle mass index (P < .001, R = 0.629), ECW/TBW (P < .001, r = -0.498), and PhA (P < .001, R = 0.550). HGS was more strongly correlated with walking speed, Barthel Index, BBS, ECW/TBW ratio, and PhA in men than women. In patients with thoracolumbar VCF, HGS is associated with walking speed, muscle mass, activities of daily living measured using the Barthel Index, and balance measured using BBS. The findings suggest that HGS is an important indicator of activities of daily living, balance, and whole-body muscle strength. Furthermore, HGS is related to PhA and ECW/TBW.