B cell-intrinsic DNase1L3 is essential for the T cell-independent type II response in mice.

T cell independent type II (TI-II) antigens, such as capsular polysaccharides, have multivalent epitopes, which induce B cell activation, plasma cell differentiation and antibody production by strongly cross-linking B cell receptors. However, the mechanism of B cell activation by TI-II antigens remains unclear. In this study, we demonstrate that DNA endonuclease DNase1L3 (also termed DNase γ) is required for the TI-II response. The production of antigen-specific antibodies was severely diminished in DNase1L3-deficient mice upon immunization with TI-II antigens, but not with T cell dependent (TD) antigens. Bone marrow chimeric mice and B cell transfer experiments revealed that B cell-intrinsic DNase1L3 was required for the TI-II response. DNase1L3-deficient B cells were defective in cell proliferation and plasma cell differentiation in the TI-II response in vivo as well as in vitro, which was not rescued by co-culture with DNase1L3-sufficient B cells in vitro, disproving an involvement of a secretory DNase1L3. In vitro stimulation with TI-II antigen transiently increased expression of DNase1L3 and its translocation into the nucleus. RNA-seq analysis of ex vivo B cells that had responded to TI-II antigen in vivo revealed a marked reduction of Myc-target gene sets in DNase1L3-deficient B cells. Expression of IRF4, a gene that Myc targets, was diminished in the ex vivo DNase1L3-deficient B cells, in which forced expression of IRF4 restored the TI-II response in vivo. These data revealed an unexpected role of DNase1L3 in a missing link between B cell receptor signaling and B cell activation in the TI-II response, giving a valuable clue to molecularly dissect this response.

The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation.

The breast and ovarian cancer-specific tumor suppressor BRCA1, along with its heterodimer partner BRCA1-associated RING domain protein (BARD1), plays important roles in DNA repair, centrosome regulation, and transcription. To explore further functions of BRCA1/BARD1, we performed mass spectrometry analysis and identified Obg-like ATPase 1 (OLA1) as a protein that interacts with the carboxy-terminal region of BARD1. OLA1 directly bound to the amino-terminal region of BRCA1 and γ-tubulin. OLA1 localized to centrosomes in interphase and to the spindle pole in mitotic phase, and its knockdown resulted in centrosome amplification and the activation of microtubule aster formation. OLA1 with a mutation observed in breast cancer cell line, E168Q, failed to bind BRCA1 and rescue the OLA1 knockdown-induced centrosome amplification. BRCA1 variant I42V also abrogated the binding of BRCA1 to OLA1. These findings suggest that OLA1 plays an important role in centrosome regulation together with BRCA1.

Good 5-year postoperative outcomes after facet fusion using a percutaneous pedicle screw system for degenerative lumbar spondylolisthesis.

Many authors have reported no significant differences in clinical outcomes between posterolateral fusion (PLF) and interbody fusion, as well as satisfactory long-term outcomes after PLF. Facet fusion (FF), a minimally invasive evolution of PLF, has also resulted in good clinical outcomes. This study aimed to assess the clinical outcomes 5 years after FF for degenerative lumbar spondylolisthesis (DLS) and determine whether good clinical outcomes were maintained after FF. Records of 115 patients who underwent FF for single-level DLS with at least 5 years of follow-up were retrospectively studied. The therapeutic effectiveness of FF was assessed as a clinical outcome using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), the Roland-Morris Disability Questionnaire (RMDQ), and the visual analogue scale (VAS) preoperatively and at 1 and 5 years postoperatively. Computed tomography was performed for fusion confirmation. The revision surgery rate was also evaluated. The JOABPEQ category scores demonstrated therapeutic effectiveness in 81.7% of patients at 1 year postoperatively and 81.4% of patients at 5 years postoperatively for low back pain; the corresponding proportions for walking ability were 93.8% and 86.6%, respectively. There were no significant differences in therapeutic effectiveness at 1 and 5 years postoperatively for any category, including the RMDQ and VAS scores. The fusion rate was 90.4% at the final follow-up. Four patients required revision surgery for adjacent segment disease 1-5 years after the first surgery (revision surgery rate, 3.5%). Good clinical outcomes were maintained 5 years after FF, and FF had an extremely low revision surgery rate.

Good clinical outcomes in nonunion cases after facet fusion with a percutaneous pedicle screw system for degenerative lumbar spondylolisthesis.

There are many satisfactory long-term outcomes after posterolateral fusion (PLF) for degenerative lumbar spondylolisthesis (DLS); nonunion cases have also achieved good clinical outcomes. Facet fusion (FF), a minimally invasive evolution of PLF, also resulted in good clinical outcomes. We aimed to assess the course of nonunion cases after FF and determine whether the nonunion cases achieved good clinical outcomes. We retrospectively reviewed the records of 136 patients who underwent FF for DLS. Range of motion (ROM) at the fused level was measured using a flexion-extension lateral radiograph preoperatively and 1 year postoperatively. Patients were classified into the Fusion or Unconfirmed Fusion group by computed tomography (CT) 1 year postoperatively. Furthermore, patients in the Unconfirmed Fusion group were classified into the Delayed Union or Nonunion group depending on the confirmation status of FF upon the following CT. The average preoperative ROM and clinical outcomes were compared between the three groups. The Fusion, Delayed Union, and Nonunion groups had 109, 14, and 13 patients, respectively. In the Nonunion group, the average ROM significantly decreased from 13.0° preoperatively to 4.9° postoperatively. There was a significant difference in the average preoperative ROM between the groups. The larger the preoperative ROM, the fewer facets fused. There was no significant difference in clinical outcomes between the groups. Five patients (3.7%) required revision surgery for adjacent segment disease 1-5.5 years after FF. Even nonunion cases after FF achieved good clinical outcomes, likely because the unstable spondylolisthesis was stabilized. FF did not require revision surgery for nonunion itself.

Pedicle screw shift without loosening following instrumented posterior fusion: limitations of pedicle screw fixation.

The disc angle at the fused segment is extended in operative prone position, but eventually returns to preoperative neutral position within 6 months to 1 year. This study aimed to assess pedicle screw (PS) shift without loosening to identify the mechanism of the change in disc angle after posterior fusion for degenerative lumbar spondylolisthesis (DLS). Sixty-three consecutive patients who underwent facet fusion for L4 single-level DLS were retrospectively reviewed using computed tomography (CT) immediately after surgery and 6 months postoperatively. Twenty-two patients (88 PSs) in whom the disc angle had decreased by more than 4° at 6-month postoperative radiographic follow-up were selected to more readily identify and quantify PS shift. Six patients with PS loosening and/or nonunion were excluded. We reconstructed a CT plane, vertical to the cranial endplate of the vertebrae and passing through the cannula used for percutaneous PSs. Angle α, which is formed by the cranial endplate and the cannula on this plane, was measured. A change in angle α of more than 2° between the immediate postoperative period and the 6-month follow-up was defined as a PS shift. Angle α did not change by more than 2° in any of the 44 PSs in the upper vertebrae of the fused segment. In the lower vertebrae, angle α changed by more than 2° in 22 of 44 PSs. The change in angle α in the lower vertebrae (average, 2.3°) was significantly greater than that in the upper vertebrae (average, 0.2°) (P < 0.0001). The change in the disc angle was not relevant to clinical outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, the Roland-Morris Disability Questionnaire, and the visual analogue scale. The disc angle at the fused segment returned to preoperative neutral position due to PS shift without loosening, mainly in the lower vertebrae. PS shift is caused by bone remodeling in response to biomechanical load, similar to that in orthodontic tooth movement. As PS has limited ability to maintain a lordotic disc angle, even with the insertion of a cage, lumbar alignment will return to preoperative neutral position owing to cage subsidence or adjacent segment disease. These findings might indicate that it is not necessary to correct the spinal alignment for DLS.

A simple formula for predicting diameter of safely inserted cortical bone trajectory screws for fixation of the lower lumbar spine.

BACKGROUND: Cortical bone trajectory (CBT) screws are popular for spinal fixation, but their ideal diameter has not been determined. Studies using postoperative computed tomography (CT) have revealed ample bone marrow space around 5.5-mm screws, which are commonly used. However, evidence indicates that a larger screw diameter provides a greater fixation strength. This study aimed to develop a generalizable formula for computing the diameter of CBT screws that could be inserted safely for fixation of the lower lumbar spine. METHODS: Records of 44 consecutive patients who had undergone posterior fusion with CBT screws for single-level degenerative lumbar spondylolisthesis were retrospectively reviewed. We estimated the maximum diameter for conventional pedicle screws by the minimum diameter of the pedicle using preoperative CT (PSD). We measured the minimum endosteal diameter of the pedicle on the reconstructed plane of the postoperative CT which passed through the cannula used for the screw and estimated the maximum diameter for the CBT screws that could be inserted within the bone marrow space of the pedicle (CBTD). RESULTS: Among the 176 pedicles measured, there were 151 (85.8%) with a PSD of 8.5 mm and 13, 7.5 mm. Because of a slight pedicle wall breach, 13 screws were excluded from the sample. There were 64 (39.3%) screws with a CBTD of 8.5 mm; 45, 7.5 mm; and 40, 6.5 mm. Of 163 screws, 156 (95.7%) had PSD minus CBTD ≤2 mm for each pedicle. PSD minus the minimum outer cortical diameter was ≤1 mm for each pedicle in 155 (95.1%) screws. CONCLUSION: Our results show that CBT screws with a diameter 1 mm smaller than the endosteal diameter of the pedicle were inserted safely. STUDY: Design: Clinical study.

Reproducibility in the global indices for multifocal visual evoked potentials and Humphrey visual fields in controls and glaucomatous eyes within a 2-year period.

PURPOSE: In previous studies, we applied receiver operating characteristic curve analysis to the signal-to-noise ratio distributions in the signal and noise windows of multifocal VEP (mfVEP) response. The areas under the curve thus obtained (SNR-AUC) were found to quantitatively detect glaucomatous visual field damage. The present study evaluated the reproducibility of SNR-AUC and the Humphrey visual field (HVF) global indices in 37 eyes with primary open angle glaucoma (POAG; POAG group) and in 30 controls (control group) within a 2-year period. METHODS: The HVF SITA standard 24-2 and mfVEP were recorded at three separate sessions for each individual. The intersession variability for SNR-AUC, mean deviation (MD), and pattern standard deviation (PSD) was evaluated using the repeated measures of analysis of variance and Bland-Altman plots. The logarithmically converted coefficients of variation (CV) of PSD and SNR-AUC were compared between the control and POAG groups. Linear regression analyses were performed on the logarithmic CV of SNR-AUC against the average MD, PSD, and SNR-AUC. RESULTS: SNR-AUC in the POAG group was significantly lower and its CV was greater compared with the control group (P < 0.0001). MD value recorded at the third visit had significantly improved than that at the first visit in the control group (analysis of variance, P = 0.03), whereas PSD value was significantly worse in the POAG group (P = 0.024). In the POAG group, SNR-AUC CV increased as the glaucoma stage became more advanced when evaluated by any functional parameters tested (i.e., MD, PSD, or SNR-AUC). CONCLUSIONS: The SNR-AUC of mfVEP showed a high reproducibility in control group, whereas it fluctuated more in the POAG group according to the disease severity. MD in the control group and PSD in POAG group fluctuated among sessions during the 2-year period.

Neuroprotective therapy with granulocyte colony-stimulating factor in acute spinal cord injury: a comparison with high-dose methylprednisolone as a historical control.

PURPOSE: We performed a phase I/IIa clinical trial and confirmed the safety and feasibility of granulocyte colony-stimulating factor (G-CSF) as neuroprotective therapy in patients with acute spinal cord injury (SCI). In this study, we retrospectively analyzed the clinical outcome in SCI patients treated with G-CSF and compared these results to a historical cohort of SCI patients treated with high-dose methylprednisolone sodium succinate (MPSS). METHODS: In the G-CSF group (n = 28), patients were treated from August 2009 to July 2012 within 48 h of the injury, and G-CSF (10 µg/kg/day) was administered intravenously for five consecutive days. In the MPSS group (n = 34), patients underwent high-dose MPSS therapy from August 2003 to July 2005 following the NASCIS II protocol. We evaluated the ASIA motor score and the AIS grade elevation between the time of treatment and 3-month follow-up and adverse events. RESULTS: The ΔASIA motor score was significantly higher in the G-CSF group than in the MPSS group (p < 0.01). When we compared AIS grade elevation in patients with AIS grades B/C incomplete paralysis, 17.9% of patients in the G-CSF group had an AIS grade elevation of two steps compared to 0% of patients in the MPSS group (p < 0.05), and the incidence of pneumonia was significantly higher in the MPSS group (42.9%) compared to the G-CSF group (8.3%) (p < 0.05). CONCLUSIONS: These results suggest that G-CSF administration is safe and effective, but a prospective randomized controlled clinical trial is needed to compare the efficacy of MPSS versus G-CSF treatment in patients with SCI.

Effect of refractive errors on multifocal VEP responses and standard automated perimetry tests in a single population.

BACKGROUND: We have previously reported that the degree of signal-to-noise ratio (SNR) distribution overlaps between a signal window and a noise window in multifocal VEP (mfVEP) responses, which is determined by the area under the receiver-operating characteristic curve termed SNR-AUC, can quantitatively detect glaucomatous visual functional damage. However, the effect of high myopia on this parameter is not yet known. METHODS: SNR-AUC, total deviation, and retinal sensitivity on the Humphrey visual field (HVF) test were compared among 34 eyes>-6 diopters (control) and 21 eyes≤-6 diopters (high myopia), both of which were ophthalmoscopically normal and had a best-corrected visual acuity of 20/20. The mfVEP and HVF parameters were obtained from stimulus areas that corresponded to both HVF 24-2 and 10-2 programs. RESULTS: Both the HVF 24-2 total deviation and the SNR-AUC obtained from 60 sectors in high-myopia patients were significantly lower compared with controls (P=0.045 and P=0.003, respectively). The SNR-AUC obtained from the central 36 sectors that corresponded to the HVF 10-2 area in high-myopia patients was also significantly lower than that of the controls (P=0.01). Multiple regression analyses demonstrated that age and refractive error were significantly associated with retinal sensitivity on the HVF 24-2 and SNR-AUC for the whole field and central field, respectively. CONCLUSIONS: High myopia reduces the SNR-AUC of mfVEP responses, even with refractive correction. A normative database should be separately established for high myopes to evaluate the mfVEP responses obtained from highly myopic glaucoma patients.

Comparison of facet fusion rates and clinical outcomes between cortical bone trajectory screw and percutaneous pedicle screw fixation for degenerative lumbar spondylolisthesis.

BACKGROUND CONTEXT: Cortical bone trajectory (CBT) screws have been introduced as an alternative technique for pedicle screw (PS) insertion because they have greater contact with the cortex and a greater uniaxial pullout load than traditional PS. CBT screwing can also minimize muscle dissection. However, CBT screws and traditional PSs have not yet been compared in terms of fusion rates and clinical outcomes for particular operative procedures. PURPOSE: This study aimed to assess the fusion rate and clinical outcomes of facet fusion (FF) fixed with CBT screws (CBT-FF) and to compare them with those of FF fixed with percutaneous PS (PPS-FF). STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Records of 68 patients who underwent CBT-FF for single-level degenerative lumbar spondylolisthesis (DLS) with at least 1 year of follow-up were retrospectively reviewed. The control group comprised 143 patients who underwent PPS-FF under the same conditions. OUTCOME MEASURES: Computed tomography was performed to confirm fusion. Therapeutic effectiveness was assessed as a clinical outcome using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire (RMDQ), and visual analog scale (VAS) preoperatively and 1 year postoperatively. The rate of revision surgery was also calculated. Intraoperative blood loss was measured. METHODS: Fusion rate, clinical outcomes, revision surgery rate, and intraoperative blood loss of CBT-FF and PPS-FF were compared. RESULTS: The CBT-FF and PPS-FF fusion rates were 91.2% and 90.1%, respectively. The JOABPEQ category scores demonstrated therapeutic effectiveness in 74.5% and 77.1% of the patients for low back pain; the corresponding proportions for walking ability were 84.7% and 89.3%, respectively. No significant differences in therapeutic effectiveness were observed for any category, including the RMDQ and VAS scores for buttock and lower limb pain. Three patients required revision surgery for adjacent segment disease between 6 months and 3.5 years after CBT-FF (revision surgery rate, 4.4%), whereas the revision surgery rate for PPS-FF was 6.3% (9/143 cases). Average intraoperative blood loss was significantly less in the CBT-FF group than in the PPS-FF group. CONCLUSIONS: Both procedures were equally useful in terms of fusion rate and clinical outcomes for DLS management.

Statistical fluctuation in zeta potential distribution of nanoliposomes measured by on-chip microcapillary electrophoresis.

The zeta potential of nanoliposomes with a diameter below 100 nm has been studied by the combined use of on-chip microcapillary electrophoresis (µCE) and sensitive fluorescence imaging. Tracking the electrophoretic migration of individual nanoliposomes has enabled the accurate evaluation of the zeta potential distribution of nanoliposomes and the first observation of its abnormal broadening due to a statistical fluctuation phenomenon specific to the "nanoscale world." The materials used for liposome preparation were phosphocholine as the neutral lipid, phosphatidylserine as the anionic lipid, and cholesterol. The size of the liposomes encapsulating calcein, a fluorescent dye used for imaging convenience, was tailored by extrusion through polycarbonate membrane filters of different pore sizes ranging from 50 to 1000 nm. The on-chip µCE system comprised a µCE chip, a laser source, an inverted microscope, and an electron-multiplying charge-coupled device camera. The electrophoresis experiment using this system revealed that the relative standard deviation of the zeta potential distribution of nanoliposomes is inversely proportional to their diameter and apparently increases below 100 nm. This abnormal broadening of zeta potential distribution of nanoliposomes is explained by prominent discreteness effect of the number of anionic lipid molecules in nanoliposomes.

Intravenous administration of granulocyte colony-stimulating factor for treating neuropathic pain associated with compression myelopathy: a phase I and IIa clinical trial.

OBJECTIVE: To confirm the feasibility and safety of granulocyte colony-stimulating factor (G-CSF) for treating spinal neuropathic pain associated with compression myelopathy, we have initiated an open-label single-center prospective clinical trial. METHODS: Between January 2009 and February 2011, 17 patients were accrued and were divided into two groups. One group included 7 patients who complained of pain associated with worsening symptoms of myelopathy (progressing myelopathy-related pain group). The other group included 10 patients who complained of pain that persisted after surgery for compression myelopathy (post-operative persistent pain group). All patients underwent intravenous administration of G-CSF (10 µg/kg/day) for 5 consecutive days. Pain severity was evaluated using a visual analog scale (VAS) before and after G-CSF administration. RESULTS: In 14 of the 17 patients, pain was relieved within several days after G-CSF administration. Pain disappeared completely in 3 patients. In the progressing myelopathy-related pain group, the mean VAS score was 71.4/100 before G-CSF administration, and decreased to 35.9/100 at 1 week after G-CSF administration (p < 0.05). In the post-operative persistent pain group, the mean VAS score was 72.0/100 before G-CSF administration, and decreased to 51.7/100 at 1 week after G-CSF administration (p < 0.05). No severe adverse events occurred during or after G-CSF administration. CONCLUSIONS: The present results provide us with the possibility that G-CSF has a pain-relieving effect for neuropathic pain in patients with compression myelopathy.

Granulocyte colony-stimulating factor reduced neuropathic pain associated with thoracic compression myelopathy: report of two cases.

CONTEXT: A clinical trial was conducted to evaluate the safety and efficacy of neuroprotective therapy using granulocyte colony-stimulating factor (G-CSF) for patients with worsening symptoms of compression myelopathy. During this trial, we found that neuropathic pain associated with thoracic myelopathy was dramatically reduced after G-CSF administration in two cases. FINDINGS: A 32-year-old man with compression of the spinal cord at levels T7-T10 complained of spastic gait associated with spontaneous severe pain from his back to his chest. G-CSF 10 µg/kg/day was administered for 5 consecutive days; his pain was reduced 1 day after the initial G-CSF administration. One month after administration, he underwent spinal fusion surgery for decompression of the spinal cord. Six months after G-CSF administration, he showed recovery from myelopathy and no recurrence of pain. A 68-year-old man with spastic gait and bilateral thigh pain caused by ossified ligamentum flavum at T11-T12 was treated with G-CSF 10 µg/kg/day for 5 days; his pain was reduced 1 day after initial administration. One month later, he underwent a T10-T12 laminectomy. Three months after G-CSF administration, his thigh pain began to attenuate. At 6 months after administration, he showed recovery from myelopathy, and his pain was still improved compared with that before administration. CONCLUSION: G-CSF may have a therapeutic effect on spinal neuropathic pain.

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, Part 1: a phase I and IIa clinical trial.

OBJECTIVE: Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy. METHODS: We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 µg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy. RESULTS: G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-µg group (n=10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-µg group, the mean JOA recovery rates 1 and 6 months after administration were 49.9±15.1 and 59.1±16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm3. It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment. CONCLUSION: The results indicate that G-CSF administration at 10 µg/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.

Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial.

OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF. METHODS: The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 µg/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 µg/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade. RESULTS: In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P < 0.01), and both light touch and pin prick scores improved 2 days after injection (P < 0.05) in the 10 µg group. No severe adverse effects were observed after G-CSF injection. CONCLUSION: These results indicate that intravenous administration of G-CSF (10 µg/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.

Cervical polyps in early pregnancy are a risk factor for late abortion and spontaneous preterm birth: A retrospective cohort study.

OBJECTIVE: To determine the association between cervical polyps in early pregnancy and late abortion and spontaneous preterm birth (SPTB). We also aimed to explore the relationship between cervical polyps and cervical insufficiency in the second trimester. METHODS: We conducted a retrospective cohort study of 2941 singleton pregnant women between January 2010 and December 2015. The frequency of late abortion and SPTB (before 28, 34, or 37 weeks of pregnancy) was compared between the two groups of 142 (4.8%) patients who had cervical polyps early in the pregnancy (P group) and 2799 who did not (non-P group). Multivariate analysis was performed to identify risk factors for late abortion and SPTB. RESULTS: The incidence of late abortion and SPTB was significantly higher in the P group than in the non-P group. Cervical polyps in early pregnancy were selected as independent risk factors for late abortion and SPTB before 28, 34, or 37 weeks of pregnancy. The P group had a significantly higher rate of cases requiring therapeutic cervical cerclage than the non-P group. CONCLUSION: Cervical polyps in early pregnancy are risk factors for late abortion and SPTB. They are also associated with the occurrence of cervical insufficiency.

Efficacy and Safety of Condoliase Disc Administration as a New Treatment for Lumbar Disc Herniation.

INTRODUCTION: Condoliase is a newly approved drug that improves symptoms associated with lumbar disk herniation (LDH) by intradiscal administration. This study aimed to evaluate the mid-term outcomes of condoliase injection, examine the adverse events, including cases that required surgery after condoliase administration, and verify cases in which condoliase could be effective. METHODS: We enrolled patients with LDH who were treated conservatively for at least six weeks and received condoliase. We assessed the visual analog scale (VAS) score, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, disk height, and disk degeneration for up to 6 months, and we examined the complications. Furthermore, a 50% or more improvement in leg pain VAS score was considered effective. Factors related to symptom improvement were investigated by determining whether lower limb pain improved in six months. RESULTS: In total, 84 patients were recruited (52 men, 32 women; mean age, 44.2 ± 17.1 [16-86 years]). The duration of illness was 6.7 ± 6.8 (1.5-30) months. All patient-based outcomes significantly improved at 4 weeks after the administration compared with pretreatment. The intervertebral disc height decreased significantly at four weeks after condoliase administration compared with that before administration. Progression of intervertebral disc degeneration occurred in 50% of the patients. Eleven patients underwent herniotomy due to poor treatment effects. Moreover, treatment in 77.4% of the patients was considered effective. A logistic regression analysis revealed that L5/S1 disk administration (p = 0.029; odds ratio, 5.94; 95% confidence interval, 1.20-29.45) were significantly associated with clinical effectiveness. CONCLUSIONS: Condoliase disk administration improved pain and quality of life over time. Condoliase disk administration was more effective in L5/S1 intervertebral administration.

Deep Learning Models for Histopathological Classification of Gastric and Colonic Epithelial Tumours.

Histopathological classification of gastric and colonic epithelial tumours is one of the routine pathological diagnosis tasks for pathologists. Computational pathology techniques based on Artificial intelligence (AI) would be of high benefit in easing the ever increasing workloads on pathologists, especially in regions that have shortages in access to pathological diagnosis services. In this study, we trained convolutional neural networks (CNNs) and recurrent neural networks (RNNs) on biopsy histopathology whole-slide images (WSIs) of stomach and colon. The models were trained to classify WSI into adenocarcinoma, adenoma, and non-neoplastic. We evaluated our models on three independent test sets each, achieving area under the curves (AUCs) up to 0.97 and 0.99 for gastric adenocarcinoma and adenoma, respectively, and 0.96 and 0.99 for colonic adenocarcinoma and adenoma respectively. The results demonstrate the generalisation ability of our models and the high promising potential of deployment in a practical histopathological diagnostic workflow system.

Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice.

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.