Capsule formation induced by flow.

Physical compartments are essential for the origin of life. While lipid vesicles are commonly regarded as precursors of cell membranes, we propose a simpler and more primitive model based on proteinoids. Proteinoids are macromolecules formed by the thermal polymerization of amino acids, mimicking primitive proteins. They self-assemble into spherical microspheres in water. Under a temperature gradient, proteinoid microspheres (PM) dissolve and flow, forming microcapsules with thin shells. The mechanism of this process has not yet been elucidated. We hypothesize that it involves the interplay between the dissolution and flow of PM. We tested our hypothesis by applying forced flow to the PM and observing capsule formation. We found that neither heat nor flow alone can produce capsules, confirming our hypothesis. We conclude that flow-induced capsule formation is a general phenomenon and a plausible model for the origin of physical compartments in early life.

Inner and outer penetrating spinal cord injuries lead to distinct overground walking in mice.

Spinal cord injury (SCI) is a devastating mechanical trauma. Although locomotion of model animals that mimic contusion SCI was actively examined, locomotion after penetrating SCI caused by sharp objects was not extensively studied. Severity of walking difficulty after partial transection of the spinal cord including penetrating SCI likely depends on the regions affected. Therefore, we compared beam walking and overground walking between mice after penetrating SCI at inner spinal cord region and mice with the injury at the outer region. Mice with the both penetrating SCIs did not display changes in beam walking. When appearance and movements of hindlimbs during overground walking was rated using Basso Mouse Scale for locomotion (BMS), however, mice with inner penetrating SCI showed low score shortly after the SCI. However, the score became high at later time points, as seen in contusion SCI mice. By contrast, BMS score did not decrease shortly after the outer penetrating SCI. However, the score became low 3 weeks after the SCI. As quantitative values during overground walking, movement duration in an open field were shorter at 1 day after the two penetrating SCIs. However, slower moving speed and fewer number of movement at 1 day were specific to mice with inner and outer penetrating SCIs, respectively. Moreover, BMS score was correlated with walking distance in open field only in mice with inner penetrating SCI. Thus, inner and outer penetrating SCI cause difficulty in overground walking with different severity and progress.

A bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a nonhemophilic state.

BACKGROUND: Emicizumab, a factor (F) VIIIa-function mimetic bispecific antibody (BsAb) to FIXa and FX, has become an indispensable treatment option for people with hemophilia A (PwHA). However, a small proportion of PwHA still experience bleeds even under emicizumab prophylaxis, as observed in the long-term outcomes of clinical studies. A more potent BsAb may be desirable for such patients. OBJECTIVES: To identify a potent BsAb to FIXa and FX, NXT007, surpassing emicizumab by in vitro and in vivo evaluation. METHODS: New pairs of light chains for emicizumab's heavy chains were screened from phage libraries, and subsequent antibody optimization was performed. For in vitro evaluation, thrombin generation assays were performed with hemophilia A plasma. In vivo hemostatic activity was evaluated in a nonhuman primate model of acquired hemophilia A. RESULTS: NXT007 exhibited an in vitro thrombin generation activity comparable to the international standard activity of FVIII (100 IU/dL), much higher than emicizumab, when triggered by tissue factor. NXT007 also demonstrated a potent in vivo hemostatic activity at approximately 30-fold lower plasma concentrations than emicizumab's historical data. In terms of dose shift between NXT007 and emicizumab, the in vitro and in vivo results were concordant. Regarding pharmacokinetics, NXT007 showed lower in vivo clearance than those shown by typical monoclonal antibodies, suggesting that the Fc engineering to enhance FcRn binding worked well. CONCLUSION: NXT007, a potent BsAb, was successfully created. Nonclinical results suggest that NXT007 would have a potential to keep a nonhemophilic range of coagulation potential in PwHA or to realize more convenient dosing regimens than emicizumab.

Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease.

In human celiac disease (CeD) HLA-DQ2.5 presents gluten peptides to antigen-specific CD4+ T cells, thereby instigating immune activation and enteropathy. Targeting HLA-DQ2.5 with neutralizing antibody for treating CeD may be plausible, yet using pan-HLA-DQ antibody risks affecting systemic immunity, while targeting selected gluten peptide:HLA-DQ2.5 complex (pHLA-DQ2.5) may be insufficient. Here we generate a TCR-like, neutralizing antibody (DONQ52) that broadly recognizes more than twenty-five distinct gluten pHLA-DQ2.5 through rabbit immunization with multi-epitope gluten pHLA-DQ2.5 and multidimensional optimization. Structural analyses show that the proline-rich and glutamine-rich motif of gluten epitopes critical for pathogenesis is flexibly recognized by multiple tyrosine residues present in the antibody paratope, implicating the mechanisms for the broad reactivity. In HLA-DQ2.5 transgenic mice, DONQ52 demonstrates favorable pharmacokinetics with high subcutaneous bioavailability, and blocks immunity to gluten while not affecting systemic immunity. Our results thus provide a rationale for clinical testing of DONQ52 in CeD.

Pure Red Cell Aplasia Induced by Atezolizumab in a Patient with Small-Cell Lung Cancer Successfully Treated with Steroid Therapy: A Case Report.

Introduction: Combination therapy of atezolizumab and chemotherapy has become the standard treatment for small-cell lung cancer. Immune-related adverse events (irAEs) can occur during immune checkpoint inhibitor administration. A few reports exist on pure red cell aplasia (PRCA) as an irAE after atezolizumab treatment. PRCA is characterized by normocytic-normochromic anemia, a marked decrease in reticulocytes, and a decrease in bone marrow erythroblasts. Here, we report a case of atezolizumab-induced PRCA. Case Presentation: A 69-year-old male patient was brought to the emergency department with the chief complaint of seizures. Multiple metastatic brain tumors and a mass suspected to be the primary lesion in the right hilar region were observed. After a brain biopsy, he was diagnosed with small-cell lung cancer (cT1cN0M1c stage IVB). He received four courses of carboplatin, etoposide, and atezolizumab in combination with whole-brain irradiation, which led to a partial response. After six courses of atezolizumab maintenance therapy, severe anemia (hemoglobin, 3.4 g/dL) was observed. PRCA induced by atezolizumab was diagnosed using a bone marrow biopsy performed during red blood cell transfusion. Treatment was started with prednisolone 25 mg/day (0.5 mg/kg/day). Anemia improved, and the dose was gradually reduced to 5 mg/day. Conclusion: Reports of PRCA as an irAE are rare but important; hence, we reported this case.

Risk factors for early mortality in elderly patients with unstable isolated C2 odontoid fracture treated with halo-vest or surgery.

The aim of this study was to compare in-hospital mortality of three procedures -halo-vest immobilization, anterior spinal fixation (ASF), and posterior spinal fixation (PSF)- in the treatment of elderly patients with isolated C2 odontoid fracture. We extracted data for elderly patients who were admitted with C2 odontoid fracture and treated with at least one of the three procedures (halo-vest immobilization, ASF, or PSF) during hospitalization. We conducted a generalized propensity score-based matching weight analysis to compare in-hospital mortality among the three procedures. We further investigated independent risk factors for in-hospital death. The study involved 891 patients (halo-vest, n = 463; ASF, n = 74; and PSF, n = 354) with a mean age of 78 years. In-hospital death occurred in 45 (5.1%) patients. Treatment type was not significantly associated with in-hospital mortality. Male sex (odds ratio 2.98; 95% confidence interval 1.32-6.73; p = 0.009) and a Charlson comorbidity index of ≥ 3 (odds ratio 9.18; 95% confidence interval 3.25-25.92; p < 0.001) were independent risk factors for in-hospital mortality. In conclusion, treatment type was not significantly associated with in-hospital mortality in elderly patients with isolated C2 odontoid fracture. Halo-vest immobilization can help to avoid adverse events in patients with C2 odontoid fracture who are considered less suitable for surgical treatment.

Steroids May Be Associated With Extensive Skeletal Muscle Uptake of 18 F-FDG.

PURPOSE: The possibility of steroid administration inducing the extensive skeletal muscle uptake (ESMU) of FDG in PET scans was investigated. METHODS: From 8923 consecutive 18 F-FDG PET/CT scans taken at our hospital, 23 scans (15 patients) met adult age and ESMU-positive inclusion criteria. Among the 15 patients, 13 with both ESMU-positive and -negative scans were examined for association with steroid administration. RESULTS: Extensive skeletal muscle uptake was associated with a history of steroid administration ( χ2 test: P = 0.001). Notably, 20 ESMU-positive scans and 11 ESMU-negative scans were significantly different, with 0 to 95 days (median, 18.5 days) and 0 to 708 days (median, 319.0 days) since the last steroid administration, respectively (Mann-Whitney U test, P = 0.003). A significant correlation was observed between mean skeletal muscle SUV max and the number of days since the last steroid administration (Spearman rank correlation coefficient, ρ = -0.501, P = 0.004). Specifically, the degree of ESMU tended to decrease over time, after steroid administration. From multiple regression analysis, the number of days since the last steroid administration was significantly associated with mean SUV max ( P = 0.007), but the blood glucose level was not significant ( P = 0.204), revealing that the number of days since the last steroid administration was an independent risk factor. Multicollinearity was low (the variance inflation factor was 1.007 for both the number of days since the last steroid administration and blood glucose levels). CONCLUSIONS: Steroid administration within months before PET may be one cause of ESMU.

Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4+ T cell interleukin-2 secretion.

Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an in vitro peripheral blood mononuclear cell-based assay that can be used to assess immunogenicity potential within 3 days. This method involves examining the frequency and function of interleukin (IL)-2-secreting CD4+ T cells induced by therapeutic antibodies. IL-2-secreting CD4+ T cells seem to be functionally relevant to the immunogenic potential due to their proliferative activity and the expression of several cytokines. The rates of the donors responding to low and high immunogenic proteins, mAb1, and keyhole limpet hemocyanin were 1.3% and 93.5%, respectively. Seven antibodies with known rates of immunogenicity (etanercept, emicizumab, abciximab, romosozumab, blosozumab, humanized anti-human A33 antibody, and bococizumab) induced responses in 1.9%, 3.8%, 6.4%, 10.0%, 29.2%, 43.8%, and 89.5% of donors, respectively. These data are comparable with ADA incidences in clinical settings. Our results show that this assay can contribute to the swift assessment and mechanistic understanding of the immunogenicity of therapeutic antibodies.

Radiographic Predictors of Subaxial Subluxation After Atlantoaxial Fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to clarify preoperative radiographic predictors associated with the development of subaxial subluxation (SAS) after surgery. BACKGROUND: The incidence of atlantoaxial fusion for atlantoaxial instability has been increasing. SAS can develop after surgery despite atlantoaxial fusion with the optimal C1-C2 angle. We hypothesized that preoperative discordant angular contribution in the upper and subaxial cervical spine is associated with the occurrence of postoperative SAS. MATERIALS AND METHODS: Patients who underwent surgery for atlantoaxial instability with a minimum 5-year follow-up and control participants were included. The O-C2 angle, C2 slope (C2S), C2-C7 cervical lordosis (CL), and T1 slope (T1S) were measured. We focused on the angular contribution ratio in the upper cervical spine to the whole CL, and the preoperative C2/T1S ratio was defined as the ratio of C2S to T1S. RESULTS: Twenty-seven patients (SAS=11, no-SAS=16; mean age, 60.7 y old; 77.8% female; mean follow-up duration, 6.8 y) and 23 demographically matched control participants were enrolled. The SAS onset was at 4.7 postoperative years. Preoperatively, the O-C2 angle, C2-C7 CL, and T1S were comparable between the SAS, no-SAS, and control groups. The preoperative C2S and C2/T1S ratio were smaller in the SAS group than in the no-SAS or control group (C2S, 11.0 vs. 18.4 vs. 18.7 degrees; C2/T1S ratio, 0.49 vs. 0.77 vs. 0.78, P <0.05). The receiver operating characteristic curve analysis demonstrated that the C2/T1S ratio had higher specificity and similar sensitivity as a predictor of postoperative SAS than C2S (specificity: 0.90 vs. 0.87; sensitivity: 0.73 vs. 0.73). The estimated cutoff values of the C2S and C2/T1S ratio were 14 degrees and 0.58, respectively. CONCLUSIONS: The preoperative C2/T1S ratio was closely associated with postoperative SAS. Patients with a C2/T1S ratio <0.58 were at a high risk of SAS after atlantoaxial fusion. LEVEL OF EVIDENCE: Level 4.

Association Between Early Surgery and Postoperative Opioid Use in Patients With Lumbar Disc Herniation: A Propensity Score-Matching Analysis Using an Administrative Claims Database in Japan.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to investigate whether early surgery shortens the duration of opioid use in patients who underwent surgery with lumbar disc herniation. METHODS: We extracted patients who underwent surgery at least 2 weeks after they were diagnosed with lumbar disc herniation between April 2014 and May 2021. Opioid use after surgery was compared between patients who underwent surgery within 90 days (early surgery group) and 90 days or later (late surgery group). Propensity-score-matching analysis and multivariable Cox hazard regression analysis with a restricted cubic spline model were conducted to evaluate the association between the timing of surgery and termination of opioid use after surgery. RESULTS: A total of 1597 eligible patients were identified, with 807 (51%) in the early surgery group. In the propensity-score-matched cohort, the early surgery group had a significantly lower proportion of opioid use than the control group (28% vs 48%, percent difference -20%, P < .001). Multivariable Cox hazard regression analysis showed that early surgery was significantly associated with the earlier termination of opioid use (HR, 3.13; 95% CI, 1.97-4.97; P < .001). Restricted cubic spline model showed a monotonically decreased hazard ratio and decreased hazard ratio of .50 in patients who underwent surgery 111 days or later after the diagnosis. CONCLUSIONS: Early surgery, especially within 90 days, was associated with earlier opioid use termination after surgery. Regarding the duration of opioid use following surgery, surgical treatment may be preferable to perform within around 4 months after the diagnosis.

Impact of the preoperative nutritional status on postoperative kyphosis in geriatric patients undergoing cervical laminoplasty.

PURPOSE: This study aimed to determine the association of preoperative malnutrition with an increased risk of cervical kyphosis after laminoplasty in geriatric patients with cervical spondylotic myelopathy (CSM). METHODS: Geriatric patients who underwent cervical laminoplasty were included. Malnutrition was defined as a geriatric nutritional risk index < 98 before surgery. The C2-7 angle and the global alignment parameters were analyzed on standing radiographs. The postoperative kyphosis was defined as a C2-7 angle < 0° during a 2-year follow-up. RESULTS: Ninety patients without preoperative kyphotic alignment were enrolled (mean age, 73.5 years old; 41.1% female). Twenty-one patients (23.3%) had malnutrition status (74.2 years old). Preoperatively, the global alignment parameters were comparable between the malnutrition and normal nutrition groups (SVA, 43.3 mm vs. 42.4 mm; T1S, 29.7° vs. 28.4°; TPA, 21.4° vs. 17.8°), with no significant difference in the C2-7 angle (15.1° vs. 15.2°). At 2 years postoperatively, the malnutrition group showed a significantly lower C2-7 angle than the normal nutrition group (9.3° vs. 15.8°, P = 0.03). Postoperative kyphosis was more prevalent in the malnutrition group (33.3% vs. 7.2%, P = 0.005). The preoperative nutritional status and C2-7 angle were independent predictors of postoperative kyphosis. The predictive C2-7 angles differed by preoperative nutritional status (malnutrition group, 11°; normal nutrition group, 7°). CONCLUSION: Among geriatric CSM patients, preoperative malnutrition was closely associated with the increased occurrence of cervical kyphosis after laminoplasty. Our results underscore the importance of preoperative nutritional assessment and management in geriatric populations undergoing cervical spine surgery, as malnutrition is a perioperative modifiable risk factor.

A simple scoring of beam walking performance after spinal cord injury in mice.

Precise evaluation of motor functions using simple and reproducible tests for mouse models of spinal cord injury (SCI) are required. Overground walking of SCI mice has been tested by Basso Mouse Scale for locomotion (BMS). In contrast, only a few works quantify walking performances of SCI mice on narrow beams, a different task. Here, we established a novel scoring system using a single beam walking apparatus for SCI mice. The scoring system uses binary judgments of values such as retention, moving forward and reaching the goal on a beam for rating. In addition, high score was given to SCI mouse when the mouse efficiently used hindlimbs for locomotion on the beam. A high rate of concordance of the score derived from positions of hindlimbs between two observers was obtained. Mice displayed the lowest total score on the beam immediately after the SCI, then the score gradually increased like time course of BMS score. Furthermore, the total scores reflected gradation of severity of SCI in 2 strains of mice. The beam walking score proved to be strongly correlated with that of BMS score, indicating that performances between overground walking and beam walking are partly correlated in SCI mice. Collectively, the novel scoring system offers an opportunity to easily evaluate motor performances of mice with SCI.

Effect of Intraoperative Tranexamic Acid on Perioperative Major Hemorrhage Requiring Transfusion in Patients Undergoing Elective Spine Surgery: A Propensity Score-Matched Analysis Using a National Inpatient Database.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to examine whether the use of intravenous TXA in elective spine surgery is associated with reduced perioperative massive hemorrhage requiring transfusion. METHODS: We extracted all patients who underwent decompression with or without fusion surgery for the cervical, thoracic, and lumbar spine between April 2012 and March 2019. The primary outcome was the occurrence of massive hemorrhage requiring transfusion, defined as at least 560 mL of blood transfusion within 2 days of spine surgery or the requirement of additional blood transfusion from 3-7 days postoperatively. Secondary outcomes were the occurrence of thrombotic complications (pulmonary embolism, acute coronary syndrome, and stroke) and postoperative hematoma requiring additional surgery. RESULTS: We identified 83,821 eligible patients, with 9747 (12%) patients in the TXA group. Overall, massive hemorrhage requiring transfusion occurred in 781 (.9%) patients. Propensity score matching yielded 8394 pairs. In the matched cohort, the TXA group had a lower proportion of massive hemorrhage requiring transfusion than the control group (.7% vs 1.1%; P = .002). There was no significant difference in the occurrence of thrombotic complications and postoperative hematoma requiring additional surgery between both groups. The multivariable regression analysis also showed that the use of TXA was associated with significantly lower proportions of massive hemorrhage requiring transfusion (odds ratio, .62; 95% confidence interval, .43-.90; P = .012). CONCLUSIONS: In this analysis using real-world data, TXA use in elective spinal surgery was associated with reduced perioperative massive hemorrhage requiring transfusion without increasing thrombotic complications. LEVEL OF EVIDENCE: Prognostic Level Ⅲ.

mTOR-AKT Signaling in Cellular Clock Resetting Triggered by Osmotic Stress.

Aims: The circadian clock oscillates in a cell-autonomous manner with a period of ∼24 h, and the phase is regulated by various time cues such as light and temperature through multiple clock input pathways. We previously found that osmotic and oxidative stress strongly affected the circadian period and phase of cellular rhythms, and triple knockout of apoptosis signal-regulating kinase (ASK) family members, Ask1, Ask2, and Ask3, abolished the phase shift (clock resetting) induced by hyperosmotic pulse treatment. We aimed at exploring a key molecule(s) and signaling events in the clock input pathway dependent on ASK kinases. Results: The phase shift of the cellular clock induced by the hyperosmotic pulse treatment was significantly reduced by combined deficiencies of the clock(-related) genes, Dec1, Dec2, and E4 promoter-binding protein 4 (also known as Nfil3) (E4bp4). In addition, liquid chromatography mass/mass spectrometry (LC-MS/MS)-based proteomic analysis identified hyperosmotic pulse-induced phosphorylation of circadian locomotor output cycles caput (CLOCK) Ser845 in an AKT-dependent manner. We found that AKT kinase was phosphorylated at Ser473 (i.e., activated) in response to the hyperosmotic pulse experiments. Inhibition of mechanistic target of rapamycin (mTOR) kinase by Torin 1 treatment completely abolished the AKT activation, suppressed the phosphorylation of CLOCK Ser845, and blocked the clock resetting induced by the hyperosmotic pulse treatment. Innovation and Conclusions: We conclude that mTOR-AKT signaling is indispensable for the CLOCK Ser845 phosphorylation, which correlates with the clock resetting induced by the hyperosmotic pulse treatment. Immediate early induction of the clock(-related) genes and CLOCK carboxyl-terminal (C-terminal) region containing Ser845 also play important roles in the clock input pathway through redox-sensitive ASK kinases. Antioxid. Redox Signal. 37, 631-646.

The Association Between the Rotator Cuff Status and the Severity and Recovery of Weakness in the Shoulder Abductor Strength in a Case of Proximal Type Cervical Spondylotic Amyotrophy.

STUDY DESIGN: Case series study. OBJECTIVE: We aimed to clarify the prevalence of rotator cuff tear (RCT), and the association between RCT and the severity and prognosis in patients with proximal type cervical spondylotic amyotrophy (CSA). METHODS: We retrospectively analyzed 35 proximal type CSA patients who were treated conservatively. The following data was collected: age, rotator cuff status on MRI, manual muscle test (MMT) score of shoulder abductor and biceps brachii muscles both at the first visit and final follow-up. We investigated the prevalence of RCT and the association between the rotator cuff status, and the severity and recovery of upper extremity weakness in patients with proximal type CSA. RESULTS: Of the 35 patients, 21 had an RCT on MRI, indicating that the prevalence of RCT in patients with proximal type CSA was 60%. An age-adjusted analysis showed that the presence of RCT was significantly associated with the MMT score of the shoulder abductor muscles both at the first visit and at the final follow-up. The presence of RCT was significantly associated with the recovery of the shoulder abductor muscles. The size of the RCT was negatively correlated with the MMT score of the shoulder abductor muscles at the final follow-up. The size of the RCT was independently correlated with the change of the MMT score of the shoulder abductor muscles. CONCLUSION: RCT was detected in >50% in patients with proximal type CSA, and the presence and severity of RCT can be used as prognostic factors for proximal type CSA patients who are treated conservatively.

Increased Cervical Spinal Instability is Associated With the Development of Proximal-type Cervical Spondylotic Amyotrophy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: We aimed to clarify the clinical relationship between the etiology of proximal-type cervical spondylotic amyotrophy (CSA) and cervical sagittal alignment and instability. SUMMARY OF BACKGROUND DATA: Although several researchers have discussed hypotheses regarding the etiology of CSA, the trigger and mechanism underlying the onset remain unclear. METHODS: We retrospectively analyzed 52 proximal-type CSA patients (CSA group) and 60 control patients (Control group). The following data were collected: age; sex; cervical lordosis (CL); T1 slope (TS); TS-CL; C2-7 sagittal vertical axis (SVA) on x-ray in the neutral position; flexion angle; extension angle and range of motion (ROM) of C3/4, C4/5 and C5/6; and C3/4, C4/5 and C5/6 instability (translation of >3 mm for adjacent segmental segments) on dynamic x-ray. RESULTS: Compared with the Control group, the CSA group was associated with an older age (mean age, 67.6 vs. 61.1 years' old, P= 0.029) and male sex (78.8% vs. 50.0%, P= 0.002). In the CSA group, the radiographic parameters showed smaller C4/5 and C5/6 extension angles and C5/6 ROM values and a greater C3/4 flexion angle than the Control group. Furthermore, compared with the Control group, the CSA group was associated with C3/4 instability (13.5% vs. 3.3%, P= 0.049) and C4/5 (21.2% vs. 3.3%, P = 0.003). A logistic regression analysis, with adjusting for the age and sex, showed that the C3/4 flexion angle (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.08- 1.40, P =0.002), C3/4 instability (OR, 7.3; 95% CI 1.25-42.96, P =0.027) and C4/5 instability (OR, 8.1; 95% CI, 1.56-42.19, P = 0.012) were independent risk factors of CSA. CONCLUSION: This study suggested that a wide C3/4 flexion angle and high C3/4 or C4/5 spinal instability were closely associated with the etiology of proximal-type CSA.

Angiomatous Meningioma in the Craniocervical Junction.

INTRODUCTION: Spinal angiomatous meningioma arising in the craniocervical junction has not been reported. Case Presentation. A 68-year-old man presented to our hospital with pain in the back and left leg. He showed slight motor weakness in his upper extremities. Magnetic resonance imaging revealed a mass with marked enhancement in the craniocervical junction. Computed tomography angiography showed feeding vessels arising from the right vertebral artery. Preoperative embolization of the feeding vessels was performed to reduce intraoperative bleeding. Gross total resection of the tumor was achieved by debulking and piecemeal resection. The tumor attachment to the dura mater was also resected (Simpson grade 1 resection). A histopathological examination confirmed the diagnosis of an angiomatous meningioma. The patient's symptoms improved shortly after surgery. CONCLUSIONS: We achieved gross total resection of spinal angiomatous meningioma arising in the craniocervical junction. A preoperative evaluation and embolization of the feeding arteries may help prevent massive intraoperative bleeding.

Deep Ultraviolet Light-Emitting Diode Light Therapy for Fusobacterium nucleatum.

BACKGROUND: Fusobacterium nucleatum, which is associated with periodontitis and gingivitis, has been detected in colorectal cancer (CRC). METHODS: We evaluated the bactericidal effect of deep ultraviolet (DUV) light-emitting diode (LED) light therapy on F. nucleatum both qualitatively and quantitatively. Two DUV-LEDs with peak wavelengths of 265 and 280-nm were used. DNA damage to F. nucleatum was evaluated by the production of cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). RESULTS: DUV-LEDs showed a bactericidal effect on F. nucleatum. No colony growth was observed after 3 min of either 265 nm or 280 nm DUV-LED irradiation. The survival rates of F. nucleatum under 265 nm DUV-LED light irradiation dropped to 0.0014% for 10 s and to 0% for 20 s irradiation. Similarly, the survival rate of F. nucleatum under 280 nm DUV-LED light irradiation dropped to 0.00044% for 10 s and 0% for 20 s irradiation. The irradiance at the distance of 35 mm from the DUV-LED was 0.265 mW/cm2 for the 265 nm LED and 0.415 mW/cm2 for the 280 nm LED. Thus, the radiant energy for lethality was 5.3 mJ/cm2 for the 265 nm LED and 8.3 mJ/cm2 for the 280 nm LED. Amounts of CPD and 6-4PP in F. nucleatum irradiated with 265 nm DUV-LED light were 6.548 ng/µg and 1.333 ng/µg, respectively. CONCLUSIONS: DUV-LED light exerted a bactericidal effect on F. nucleatum by causing the formation of pyrimidine dimers indicative of DNA damage. Thus, DUV-LED light therapy may have the potential to prevent CRC.