Impact of incidental dural tears on postoperative outcomes in patients undergoing cervical spine surgery: a multicenter retrospective cohort study.

BACKGROUND CONTEXT: Incidental dural tear (DT) during cervical spine surgery is a feared complication. However, its impact on patient-reported outcomes (PROs) remains unclear. PURPOSE: To determine the influence of DTs on PROs 1 year after cervical spine surgery. STUDY DESIGN: Retrospective cohort. PATIENT SAMPLE: Patients undergoing elective cervical spine surgery for cervical spondylosis, ossification of the posterior longitudinal ligament (OPLL), and cervical disc herniation. OUTCOME MEASURES: Analysis included patients' characteristics, perioperative complications, and PROs both preoperatively and at 1 year postoperatively. METHODS: This study enrolled consecutive patients who underwent elective cervical spine surgery at 13 high-volume spine centers. All patients were required to complete questionnaires both preoperatively and 1 year postoperatively, which included PROs such as numerical rating scales of pain or dysesthesia for each part of the body, Neck Disability Index NDI, and Core Outcome Measures Index. Patients were divided into 2 groups based on the presence (DT+) or absence (DT-) of dural injury. Comparisons were made regarding patient background, perioperative complications, and pre and postoperative PROs. Propensity score matching was also utilized to adjust for patient background, and further comparisons were made regarding complication rates and PROs. RESULTS: Out of 2,704 patients, dural tears were identified in 97 (3.6%) cases. The DT+ group had a significantly higher proportion of fixation surgeries, upper cervical surgeries, OPLL, and revision surgeries. Perioperative complications were significantly higher in the DT+ group, including intraoperative nerve damage, postoperative paralysis, surgical site infections (SSI), and cerebrovascular complications. Outcomes collected from 2,163 patients (79.9%) revealed significantly more severe neck and upper limb pain in the DT+ group. After propensity score matching, significant differences persisted in postoperative paralysis and SSI in the DT+ group, but no significant differences were observed in PROs. CONCLUSIONS: Patients with dural tears showed nearly equivalent postoperative outcomes at 1 year following cervical spine surgery compared to those without dural tears. However, the incidence of perioperative complications was higher, emphasizing the need for careful management.

Patient-Reported Outcomes and Patient Satisfaction Following Surgery for Thoracic Myelopathy.

Introduction: The association between postoperative patient-reported outcomes (PROs) and patient satisfaction remains poorly defined in patients undergoing surgery for thoracic myelopathy. This study aimed to investigate PROs and patient satisfaction following surgical intervention for thoracic myelopathy. Methods: A prospective cohort of 133 patients who underwent surgery for thoracic myelopathy at 13 hospitals between April 2017 and August 2021 was enrolled. Patient demographics and perioperative complications were recorded. PROs were assessed using questionnaires administered preoperatively and 1 year postoperatively, including the EuroQol-5 dimension, physical and mental component summaries of the 12-item Short-Form Health Survey, Oswestry Disability Index, and numerical rating scales for low back, lower extremity, and plantar pain. Patients were categorized into two groups: satisfied (very satisfied, satisfied, and slightly satisfied) and dissatisfied (neither satisfied nor dissatisfied, slightly dissatisfied, dissatisfied, and very dissatisfied). Results: The mean age of the patients was 66.5 years, comprising 87 men and 46 women. The most common diagnoses were ossification of the ligamentum flavum (48.8%) and thoracic spondylotic myelopathy (26.3%). Seventy-four (55.6%) and 59 (44.3%) patients underwent decompression surgery and underwent decompression with fusion, respectively. Eight patients required reoperation due to postoperative surgical site infection, hematoma, and insufficient decompression in four, three, and one patient. Ninety (67.7%) patients completed both the preoperative and postoperative PRO questionnaires, all of which demonstrated significant improvement. Among them, 58 (64.4%) and 32 (35.6%) reported satisfaction and dissatisfaction with their treatment, respectively. The satisfied group showed superior improvement in PROs than the dissatisfied group, although there were no significant differences in complication rates between the two groups. Conclusions: The 64.4% satisfaction rate observed in patients undergoing surgery for thoracic myelopathy was lower than that reported in previous studies on cervical or lumbar spine surgery. The dissatisfied group exhibited significantly poorer quality of life (QOL) and higher pain scores than the satisfied group.

Asciminib, a novel allosteric inhibitor of BCR-ABL1, shows synergistic effects when used in combination with imatinib with or without drug resistance.

In the treatment of chronic myeloid leukemia (CML), resistance to BCR-ABL inhibitors makes it difficult to continue treatment and is directly related to life expectancy. Therefore, asciminib was introduced to the market as a useful drug for overcoming drug resistance. While combining molecular targeted drugs is useful to avoid drug resistance, the new BCR-ABL inhibitor asciminib and conventional BCR-ABL inhibitors should be used as monotherapy in principle. Therefore, we investigated the synergistic effect and mechanism of the combination of asciminib and imatinib. We generated imatinib-resistant cells using the human CML cell line K562, examined the effects of imatinib and asciminib exposure on cell survival using the WST-8 assay, and comprehensively analyzed genetic variation related to drug resistance using RNA-seq and real-time PCR. A synergistic effect was observed when imatinib and asciminib were combined with or without imatinib resistance. Three genes, GRRP1, ESPN, and NOXA1, were extracted as the sites of action of asciminib. Asciminib in combination with BCR-ABL inhibitors may improve the therapeutic efficacy of conventional BCR-ABL inhibitors and prevent the development of resistance. Its dosage may be effective even at minimal doses that do not cause side effects. Further verification of this mechanism of action is needed. Additionally, cross-resistance between BCR-ABL inhibitors and asciminib may occur, which needs to be clarified through further validation as soon as possible.

The seminal vesicle is a juvenile hormone-responsive tissue in adult male Drosophila melanogaster.

Juvenile hormone (JH) is one of the most essential hormones controlling insect metamorphosis and physiology. While it is well known that JH affects many tissues throughout the insects life cycle, the difference in JH responsiveness and the repertoire of JH-inducible genes among different tissues has not been fully investigated. In this study, we monitored JH responsiveness in vivo using transgenic Drosophila melanogaster flies carrying a JH response element-GFP (JHRE-GFP) construct. Our data highlight the high responsiveness of the epithelial cells within the seminal vesicle, a component of the male reproductive tract, to JH. Specifically, we observe an elevation in the JHRE-GFP signal within the seminal vesicle epithelium upon JH analog administration, while suppression occurs upon knockdown of genes encoding the intracellular JH receptors, Methoprene-tolerant and germ cell-expressed. Starting from published transcriptomic and proteomics datasets, we next identified Lactate dehydrogenase as a JH-response gene expressed in the seminal vesicle epithelium, suggesting insect seminal vesicles undergo metabolic regulation by JH. Together, this study sheds new light on biology of the insect reproductive regulatory system.

Discovery of Transcription Factors Involved in the Maintenance of Resident Vascular Endothelial Stem Cell Properties.

A resident vascular endothelial stem cell (VESC) population expressing CD157 has been identified recently in mice. Herein, we identified transcription factors (TFs) regulating CD157 expression in endothelial cells (ECs) that were associated with drug resistance, angiogenesis, and EC proliferation. In the first screening, we detected 20 candidate TFs through the CD157 promoter and gene expression analyses. We found that 10 of the 20 TFs induced CD157 expression in ECs. We previously reported that 70% of CD157 VESCs were side population (SP) ECs that abundantly expressed ATP-binding cassette (ABC) transporters. Here, we found that the 10 TFs increased the expression of several ABC transporters in ECs and increased the proportion of SP ECs. Of these 10 TFs, we found that six (Atf3, Bhlhe40, Egr1, Egr2, Elf3, and Klf4) were involved in the manifestation of the SP phenotype. Furthermore, the six TFs enhanced tube formation and proliferation in ECs. Single-cell RNA sequence data in liver ECs suggested that Atf3 and Klf4 contributed to the production of CD157+ VESCs in the postnatal period. We concluded that Klf4 might be important for the development and maintenance of liver VESCs. Our work suggests that a TF network is involved in the differentiation hierarchy of VESCs.

Clinical role of crosslink augmentation during short-segment posterior lumbar interbody fusion with total facetectomy: A propensity score-matched analysis.

We investigated the clinical role of crosslink augmentation during PLIF with total facetectomy. We retrospectively reviewed 376 patients who underwent one- or two-segment PLIF with unilateral or bilateral total facetectomy between January 2017 and March 2022. The patients were categorized into two groups based on whether a crosslink was instrumented or not. Radiological outcome measurements included fusion status and implant failure rates on 12-month postoperative computed tomography. Patient-reported outcome measures included the Numerical Rating Scale for lower back pain, Oswestry Disability Index, and Short Form-12 Physical Component Summary scores, which were assessed preoperatively and at 12 months postoperatively. Surgery-related complications included surgical site infection, symptomatic implant failure, and epidural hematoma. Propensity score matching was performed to compare both groups after adjusting for confounding factors, including baseline and surgical procedural characteristics. A total of 200 cases were included in the propensity score calculation, and one-to-one matching was performed, resulting in 56 pairs with and without a crosslink. The fusion status (88.7 % vs. 85.5 %), screw loosening (14.3 % vs. 14.3 %), cage subsidence (17.9 % vs. 16.1 %), and cage dislodgement (5.4 % vs. 0 %) showed no significant difference between those with and without a crosslink, respectively. No significant differences were observed in the patient-reported outcomes or surgery-related complication rates between the groups. Crosslink augmentation during PLIF with total facetectomy is not recommended because it does not provide any radiological or clinical benefit and is associated with avoidable expenses.

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol.

INTRODUCTION: Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population. METHODS AND ANALYSIS: This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse. ETHICS AND DISSEMINATION: The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: jRCTs041220126.

Bone Turnover Markers in Patients With Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine.

STUDY DESIGN: A prospective, single-center, observational study. OBJECTIVE: To explore the association between serum levels of bone turnover markers and ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine. SUMMARY OF BACKGROUND DATA: The relationship between bone turnover markers, such as N-terminal propeptide of type I procollagen (PINP) or tartrate-resistant acid phosphate 5b (TRACP-5b), and OPLL has previously been examined. However, the correlation between these markers and thoracic OPLL, which is more severe than cervical-only OPLL, remains unclear. METHODS: This prospective study included 212 patients from a single institution with compressive spinal myelopathy and divided them into those without OPLL (Non-OPLL group, 73 patients) and those with OPLL (OPLL group, 139 patients). The OPLL group was further subdivided into cervical OPLL (C-OPLL, 92 patients) and thoracic OPLL (T-OPLL, 47 patients) groups. Patients' characteristics and biomarkers related to bone metabolism, such as calcium, inorganic phosphate (Pi), 25-hydroxyvitamin D, 1α,25 dihydroxyvitamin D, PINP, and TRACP-5b, were compared between the Non-OPLL and OPLL groups, as well as the C-OPLL and T-OPLL groups. Bone metabolism biomarkers were also compared after adjusting for age, sex, body mass index, and the presence of renal impairment using propensity score-matched analysis. RESULTS: The OPLL group had significantly lower serum levels of Pi and higher levels of PINP versus the Non-OPLL group as determined by propensity score-matched analysis. The comparison results between the C-OPLL and T-OPLL groups using a propensity score-matched analysis showed that T-OPLL patients had significantly higher concentrations of bone turnover markers, such as PINP and TRACP-5b, compared with C-OPLL patients. CONCLUSIONS: Increased systemic bone turnover may be associated with the presence of OPLL in the thoracic spine, and bone turnover markers such as PINP and TRACP-5b can help screen for thoracic OPLL.

Comparative Analysis of Microendoscopic and Open Laminectomy for Single-Level Lumbar Spinal Stenosis at L1-L2 or L2-L3.

BACKGROUND: Several reports have highlighted comparable surgical outcomes between microendoscopic laminectomy (MEL) and open laminectomy (open) for lumbar spinal stenosis. However, the unilateral approach in MEL may present challenges for the upper lumbar levels, where facet joints are located deeper inside. Our objective was to compare surgical outcomes and radiographic evaluations for single-level decompression cases at L1-L2 or L2-L3 between MEL and open laminectomy. METHODS: We analyzed patients who underwent single-level decompression for upper lumbar spinal stenosis at 12 distinguished spine centers from April 2017 to September 2021. Baseline demographics, preoperative, and 1-year postoperative patient-reported outcomes, along with imaging parameters, were compared between the MEL and open groups. To account for potential confounding, patients' backgrounds were adjusted using the inverse probability weighting method based on propensity scores. RESULTS: Among the 2487 patients undergoing decompression surgery, 118 patients (4.7%) underwent single-level decompression at L1-L2 or L2-L3. Finally, 80 patients (51 in the MEL group, 29 in the open group) with postoperative data were deemed eligible for analysis. The MEL group exhibited significantly improved postoperative EuroQol 5-Dimension values compared to the open group. Additionally, the MEL group showed a lower facet preservation rate according to computed tomography examination, whereas the open group had a higher incidence of retrolisthesis. CONCLUSIONS: Although overall surgical outcomes were similar, the MEL group demonstrated potential advantages in enhancing EuroQol 5-Dimension scores. The MEL group's lower facet preservation rate did not translate into a higher postoperative instability rate.

Atypical cell death and insufficient matrix organization in long-bone growth plates from Tric-b-knockout mice.

TRIC-A and TRIC-B proteins form homotrimeric cation-permeable channels in the endoplasmic reticulum (ER) and nuclear membranes and are thought to contribute to counterionic flux coupled with store Ca2+ release in various cell types. Serious mutations in the TRIC-B (also referred to as TMEM38B) locus cause autosomal recessive osteogenesis imperfecta (OI), which is characterized by insufficient bone mineralization. We have reported that Tric-b-knockout mice can be used as an OI model; Tric-b deficiency deranges ER Ca2+ handling and thus reduces extracellular matrix (ECM) synthesis in osteoblasts, leading to poor mineralization. Here we report irregular cell death and insufficient ECM in long-bone growth plates from Tric-b-knockout embryos. In the knockout growth plate chondrocytes, excess pro-collagen fibers were occasionally accumulated in severely dilated ER elements. Of the major ER stress pathways, activated PERK/eIF2α (PKR-like ER kinase/ eukaryotic initiation factor 2α) signaling seemed to inordinately alter gene expression to induce apoptosis-related proteins including CHOP (CCAAT/enhancer binding protein homologous protein) and caspase 12 in the knockout chondrocytes. Ca2+ imaging detected aberrant Ca2+ handling in the knockout chondrocytes; ER Ca2+ release was impaired, while cytoplasmic Ca2+ level was elevated. Our observations suggest that Tric-b deficiency directs growth plate chondrocytes to pro-apoptotic states by compromising cellular Ca2+-handling and exacerbating ER stress response, leading to impaired ECM synthesis and accidental cell death.

Does surgical site infection affect patient-reported outcomes after spinal surgery? A multicenter cohort study.

BACKGROUND: Surgical site infections are common in spinal surgeries. It is uncertain whether outcomes in spine surgery patients with vs. without surgical site infection are equivalent. Therefore, we assessed the effects of surgical site infection on postoperative patient-reported outcomes. METHODS: We enrolled patients who underwent elective spine surgery at 12 hospitals between April 2017 and February 2020. We collected data regarding the patients' backgrounds, operative factors, and incidence of surgical site infection. Data for patient-reported outcomes, namely numerical rating scale, Neck Disability Index/Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 1 year postoperatively. We divided the patients into with and without surgical site infection groups. Multivariate logistic regression analyses were performed to identify the risk factors for surgical site infection. Using propensity score matching, we obtained matched surgical site infection-negative and -positive groups. Student's t-test was used for comparisons of continuous variables, and Pearson's chi-square test was used to compare categorical variables between the two matched groups and two unmatched groups. RESULTS: We enrolled 8861 patients in this study; 74 (0.8 %) developed surgical site infections. Cervical spine surgery and American Society of Anesthesiologists physical status classification ≥3 were identified as risk factors; microendoscopy was identified as a protective factor. Using propensity score matching, we compared surgical site infection-positive and -negative groups (74 in each group). No significant difference was found in postoperative pain or dysesthesia of the lower back, buttock, leg, and plantar area between the groups. When comparing preoperative with postoperative pain and dysesthesia, statistically significant improvement was observed for both variables in both groups (p < 0.01 for all variables). No significant differences were observed in postoperative outcomes between the matched surgical site infection-positive and -negative groups. CONCLUSIONS: Patients with surgical site infections had comparable postoperative outcomes to those without surgical site infections.

Steroid hormone signaling: What we can learn from insect models.

Ecdysteroids are a group of steroid hormones in arthropods with pleiotropic functions throughout their life history. Ecdysteroid research in insects has made a significant contribution to our current understanding of steroid hormone signaling in metazoans, but how far can we extrapolate our findings in insects to other systems, such as mammals? In this chapter, we compare steroid hormone signaling in insects and mammals from multiple perspectives and discuss similarities and differences between the two lineages. We also highlight a few understudied areas and remaining questions of steroid hormone biology in metazoans and propose potential future research directions.

Clinical efficacy of assessment of swallowing ability for pneumonia and other assessment tools for occurrence and mortality from pneumonia among older inpatients in a long-term care hospital.

BACKGROUND: Aspiration pneumonia is an important condition in elderly patients and detecting dysphagia early can help clinicians identify patients with a high risk of aspiration pneumonia. We previously reported the usefulness of the Assessment of Swallowing Ability for Pneumonia (ASAP) in predicting the occurrence of and mortality from pneumonia in patients in acute care hospitals; however, there are very few reports on the utility of this screening test for patients in stable condition. METHODS: Elderly patients in stable condition (n = 133) without pneumonia were prospectively enrolled. Associations between ASAP, Functional Independence Measure (FIM), Controlling Nutrition Status (CONUT), and Charlson Co-morbidity Index (CCI) scores and occurrence of/mortality from pneumonia during hospitalization were evaluated. RESULTS: The occurrence of pneumonia was observed in 27 (20.3%) patients, and 18 (13.5%) died during hospitalization. Multivariate analysis showed that low ASAP score and low FIM motor were independent predictors for the occurrence of pneumonia, and low ASAP score was an independent predictor for mortality from pneumonia. Areas under the curve for ASAP, FIM motor, FIM cognition, and CONUT scores were 0.895 (95% confidence interval [CI], 0.829-0.960), 0.913 (95% CI, 0.860-0.968), 0.841 (95% CI, 0.761-0.921), and 0.753 (95% CI, 0.649-0.858), respectively, for occurrence, and 0.881 (95% CI, 0.807-0.955), 0.904 (95% CI, 0.860-0.949), 0.829 (95% CI, 0.727-0.931), 0.746 (95% CI, 0.617-0.874), respectively, for mortality. CONCLUSION: The ASAP and FIM motor are useful for predicting the occurrence of and mortality from pneumonia in elderly inpatients in long-term care hospitals.

Upper cervical anterior fusion to C2 with temporary infrahyoid muscle detachment: a clinical case series and description of surgical technique.

BACKGROUND: Anterior cervical spine surgery to C2 (ACSS-C2) is a challenging procedure that often results in postoperative persistent dysphagia or dyspnea due to injury to the internal branch of the superior laryngeal nerve (iSLN) or the relatively narrow and soft oropharynx. This study aimed to describe the surgical outcomes of our modified approach with temporary infrahyoid muscle detachment during ACSS-C2. METHODS: Patients who underwent ACSS-C2 at two institutions between June 2015 and January 2022 were prospectively enrolled. Intraoperatively, we performed temporary detachment of the infrahyoid muscle from the hyoid bone to improve laryngeal mobility and accessibility to C2. This procedure also allowed for the easy identification and preservation of the iSLN. We retrospectively investigated the surgery-related complications and outcomes of bony fusion. RESULTS: Twelve patients were enrolled in this study; five and seven patients underwent single- and multi-level fusion surgery, respectively. Intraoperative preservation of the iSLN and proper visualization of C2 were achieved in all cases. Subsequent decompression and instrumentation were successfully performed. Two older patients (78 and 81 years) who underwent multi-level fusion experienced transient postoperative dysphagia. None of the patients required unplanned reintubation or revision surgery because of instrumentation failure. Solid bony fusion was achieved in all cases. CONCLUSIONS: Our modified approach with temporary infrahyoid muscle detachment during ACSS-C2 reduces the incidence of postoperative persistent dysphagia and dyspnea. However, in older patients at high risk for postoperative dysphagia, multi-level fusion should be avoided, and alternative procedures should be considered.

Relationship between serum sodium level at dialysis initiation and all-cause mortality.

BACKGROUND: Hyponatremia is a common electrolyte disorder in patients with chronic kidney disease. In addition, hyponatremia is associated with mortality in patients with chronic kidney disease, including those on dialysis. However, few studies have examined this relationship in patients with incident dialysis. METHODS: We used a database of multicenter prospective cohort studies that included 1520 incident dialysis patients. The baseline was set at the time of dialysis initiation. The enrolled patients were classified into five groups according to their serum sodium levels (< 130 mEq/L, 130-134 mEq/L, 135-139 mEq/L, 140-144 mEq/L, and ≥ 145 mEq/L). Multivariate Cox proportional hazards analysis was conducted to determine factors associated with all-cause mortality. RESULTS: A total of 392 all-cause deaths occurred during the follow-up period. The ultrafiltration volume per body weight during the first dialysis session was more significant in the groups with the lowest and highest sodium levels. The percentage of patients using loop diuretics and thiazide was higher in the group with lower sodium levels (< 130 mEq/L and 130-134 mEq/L). All-cause mortality was significantly different among the five groups (p = 0.025). Multivariate analysis indicated that all-cause mortality was significantly higher in the group with the lowest sodium level compared to the group with a serum sodium level of 135-139 mEq/L (hazard ratio: 1.61, 95% confidence interval: 1.04-2.49). CONCLUSION: Hyponatremia of < 130 mEq/L at dialysis initiation was significantly associated with all-cause mortality. We considered the results relevant to underlying conditions, including cardiovascular disease and medications.

Cancer apelin receptor suppresses vascular mimicry in malignant melanoma.

Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin-apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin-APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin-APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial-mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-ß/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.

Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors-targets of neonicotinoids.

Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dß1, and Dß2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dß3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dß3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity.

Noninvasive Skin Autofluorescence of Advanced Glycation End Products for Detecting Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine.

STUDY DESIGN: A single-center prospective observational study. OBJECTIVE: The aim was to clarify the usefulness of assessing advanced glycation end products (AGEs) by noninvasive skin autofluorescence in patients with ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: AGE accumulation is associated with various systemic disorders, including aging, diabetes mellitus, and obesity. AGEs have also been associated with OPLL, but their assessment by noninvasive skin autofluorescence has not been yet studied in these patients. MATERIALS AND METHODS: We enrolled patients with degenerative spinal spondylosis and divided them into non-OPLL and OPLL groups. The OPLL group was further subdivided into cervical OPLL (C-OPLL) and thoracic OPLL (T-OPLL) groups. We compared patients' characteristics, serum laboratory data (i.e. hemoglobin A1c, total cholesterol, creatinine, and estimated glomerular filtration rate), and the skin autofluorescence intensity of AGEs (the AGE score) between the non-OPLL and OPLL groups and among the non-OPLL, C-OPLL, T-OPLL groups. Finally, the association of the AGE score with the presence of C-OPLL or T-OPLL was assessed by multinomial logistic regression. RESULTS: Among the 240 eligible patients, 102 were in the non-OPLL group and 138 were in the OPLL group (92 with C-OPLL and 46 with T-OPLL). We observed no significant difference in the AGE score between the non-OPLL and OPLL groups, but when comparing the score among the non-OPLL, C-OPLL, and T-OPLL groups, we found that the T-OPLL group had a significantly higher AGE score. The results of multinomial regression analysis showed that a higher AGE score was significantly associated with T-OPLL (odds ratio: 1.46; 95% CI: 1.01-2.11; P=0.044). CONCLUSION: The AGE score determined by noninvasive skin autofluorescence could help to screen for OPLL in the thoracic spine.

Association Between Deep Posterior Cervical Paraspinal Muscle Morphology and Clinical Features in Patients With Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To clarify the association of the paraspinal muscle area and composition with clinical features in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: Consecutive patients with cervical OPLL who underwent cervical magnetic resonance imaging (MRI) before surgery were reviewed. The cross-sectional area (CSA) and fatty infiltration ratio (FI%) of deep posterior cervical paraspinal muscles (multifidus [MF] and semispinalis cervicis [SCer]) were examined. We assessed the association of paraspinal muscle measurements with the clinical characteristics and clinical outcomes, such as Neck Disability Index (NDI) score. Moreover, we divided the patients into 2 groups according to the extent of the ossified lesion (segmental and localized [OPLL-SL] and continuous and mixed [OPLL-CM] groups) and compared these variables between the 2 groups. RESULTS: 49 patients with cervical OPLL were enrolled in this study. The FI% of the paraspinal muscles was significantly associated with the number of vertebrae (ρ = 0.283, p = 0.049) or maximum occupancy ratio of OPLL (ρ = 0.397, p = 0.005). The comparative study results indicated that the NDI score was significantly worse (OPLL-SL, 22.9 ± 13.7 vs. OPLL-CM, 34.4 ± 13.7) and FI% of SCer higher (OPLL-SL, 9.1 ± 1.7% vs. OPLL-CM, 11.1 ± 3.7%) in the OPLL-CM group than those in the OPLL-SL group. CONCLUSIONS: Our results suggest that OPLL severity may be associated with fatty infiltration of deep posterior cervical paraspinal muscles, which could affect neck disability in patients with cervical OPLL.

Short-term resveratrol treatment restored the quality of oocytes in aging mice.

The quality of oocytes declines by aging, resulting in their low competences for fertility. Here, resveratrol treatment showed increases in the rates of implantation and live offspring as well as decreases in the abortion rate as short as one week after treatment, although the number of ovulated oocytes and the rates of fertilization and blastocyst formation were not changed following resveratrol treatment. Resveratrol treatment did not cause abnormalities mouse estrous cycles and body weights. No abnormality was detected in both fetuses and placentas after 22 weeks of resveratrol treatment and the fetuses had normal fertility. Positive correlations were found between serum resveratrol levels and pregnancy and live offspring rates as well as ovarian expression levels of Sirt1, Sirt3, Sirt4, Sirt5, and Sirt7. The mitochondrial membrane potential and ATP content but not copy number of mitochondrial DNA in oocytes was increased in aging mice with resveratrol treatment. In conclusion, we demonstrated the restoration of oocyte quality in aging mice in addition to the prevention of their quality decline during aging by restoring mitochondrial functions by resveratrol treatment without adverse effects in the animals and their offspring.