Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypical femoral fractures in patients with rheumatoid arthritis.

The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.

A Novel IFITM5 Variant Associated with Phenotype of Osteoporosis with Calvarial Doughnut Lesions: A Case Report.

Osteogenesis imperfecta (OI) and other decreased bone density disorders comprise a heterogeneous group of heritable diseases with skeletal fragility. Recently, it was discovered that mutations in SGMS2, encoding sphingomyelin synthetase 2, result in aberrant sphingomyelin metabolism and lead to a novel form of OI termed osteoporosis with calvarial doughnut lesions (OP-CDL) with moderate to severe skeletal fragility and variable cranial hyperostotic lesions. This study describes a Japanese family with the skeletal phenotype of OP-CDL. The affected individuals have moderately severe, childhood-onset skeletal fragility with multiple long-bone fractures, scoliosis and bone deformities. In addition, they exhibit multiple CDLs or calvarial bumps with central radiolucency and peripheral radiopacity. However, SGMS2 sequencing was normal. Instead, whole-exome sequencing identified a novel IFITM5 missense mutation c.143A>G (p.N48S) (classified as a VUS by ACMG). IFITM5 encodes an osteoblast-restricted protein BRIL and a recurrent c.-14C>T mutation in its 5' UTR region results in OI type V, a distinctive subtype of OI associated with hyperplastic callus formation and ossification of the interosseous membranes. The patients described here have a phenotype clearly different from OI type V and with hyperostotic cranial lesions, feature previously unreported in association with IFITM5. Our findings expand the genetic spectrum of OP-CDL, indicate diverse phenotypic consequences of pathogenic IFITM5 variants, and imply an important role for BRIL in cranial skeletogenesis.

Longitudinal sleep duration and subsequent development of cancer in the Japanese population.

Evidence of the association between sleep duration and subsequent cancer development is inconsistent. The aim of this study was to evaluate the association between sleep duration and any type of cancer incidences in the Japanese population. A retrospective longitudinal study was conducted from 2005 to 2018 at St. Luke's International Hospital, Tokyo, Japan. All participants were ≥50 years old and underwent health check-ups at the Center for Preventive medicine at the hospital. Our outcome was the development of any type of cancer during follow-up. The outcomes were evaluated across the sleep duration categories with a longitudinal analysis adjusted for potential confounders. A total of 24,873 participants were included in this study; the mean age was 59.1 years (standard deviation: 7.2) and 13,258 (53.3%) were male. During the median follow-up of 1,841 days (interquartile range: 821-3,246); 2,544 (10.2%) developed a type of cancer. After adjusting for potential confounders, the development of any type of cancer did not vary across the sleep duration categories compared to the reference group (6-7 hours) (adjusted ORs were from 0.95 to 1.15, all were statistically insignificant). In terms of each type of cancer, sleep duration was associated with malignant neoplasms of digestive organs associated with a U shape and long sleep duration was associated with a higher incidence of malignant neoplasms of lymphoid, hematopoietic, and related tissues (OR 15.9, 95%CI: 1.61-156) among females. According to our longitudinal study, there was no clear association between sleep duration and subsequent development of any type of cancer. However, sleep duration was associated with certain types of cancer such as that of digestive organs, lymphoid, hematopoietic, and related tissues in females, and genital organs in males.

Synaptotagmin XIII expression and peritoneal metastasis in gastric cancer.

BACKGROUND: Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. METHODS: Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein was determined in gastric tissues from patients with gastric cancer. RESULTS: Synaptotagmin XIII (SYT13) was expressed at significantly higher levels in patients with peritoneal recurrence, but not in those with hepatic or distant lymph node recurrence. Inhibition of SYT13 expression in a gastric cancer cell line transfected with SYT13-specific siRNA (siSYT13) was associated with decreased invasion and migration ability of the cells, but not with proliferation and apoptosis. Intraperitoneal administration of siSYT13 significantly inhibited the growth of peritoneal nodules and prolonged survival in mice. In an analysis of 200 patients with gastric cancer, SYT13 expression in primary gastric cancer tissues was significantly greater in patients with peritoneal recurrence or metastasis. A high level of SYT13 expression in primary gastric cancer tissues was an independent risk factor for peritoneal recurrence. CONCLUSION: SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.

Spin Current Generation Using a Surface Acoustic Wave Generated via Spin-Rotation Coupling.

We demonstrate the generation of alternating spin current (SC) via spin-rotation coupling (SRC) using a surface acoustic wave (SAW) in a Cu film. Ferromagnetic resonance caused by injecting SAWs was observed in a Ni-Fe film attached to a Cu film, with the resonance further found to be suppressed through the insertion of a SiO_{2} film into the interface. The intensity of the resonance depended on the angle between the wave vector of the SAW and the magnetization of the Ni-Fe film. This angular dependence is explicable in terms of the presence of spin transfer torque from a SC generated via SRC.

Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy.

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.

Relationship between blood culture time to positivity, mortality rate, and severity of bacteremia.

OBJECTIVES: We investigated the association between patient severity or mortality and time to positivity in bacteremia caused by various pathogens. PATIENTS AND METHODS: This single-center retrospective study included patients with positive blood culture results. RESULTS: Longer time to positivity was associated with 30-day mortality for Staphylococcus aureus (221 cases, time to positivity: 17.4 h in the 30-day mortality group vs. 14.1 h in the survival group). Age, chronic kidney disease, cerebrovascular disease, hypertensive drug use, consciousness disorder, and minimal systolic blood pressure were significant predictors of 30-day mortality. For S. aureus, mortality within 30 days was significantly higher when time to positivity was > 24 h (p = 0.04). The time to positivity of Streptococcus pneumoniae, α, ß-hemolytic Streptococcus, Enterococcus sp., Enterobacteriaceae, glucose-nonfermenting Gram-negative rods, Candida sp., and anaerobe was not significantly associated with 30-day mortality. CONCLUSIONS: Among various pathogens, time to positivity > 24 h was associated with 30-day mortality for S. aureus.

Optimal prostate-specific antigen screening interval for prostate cancer.

BACKGROUND: To identify the optimal interval for repeat prostate-specific antigen (PSA) testing to screen for prostate cancer in healthy adults. PATIENTS AND METHODS: A retrospective cohort study was conducted on 7332 healthy males without prostate cancer at baseline from 2005 to 2008. Participants underwent annual health checkups including PSA testing at the Center for Preventive Medicine in Japan. Participants with high PSA (≥ 4.0 ng/ml) underwent further examination for prostate cancer. A subgroup analysis was conducted age group (<50 years, ≥ 50 years). RESULTS: Mean age was 50 years. Mean PSA at baseline was 1.2 ng/ml. In over 50-year group, for those with initial PSA of <1.0, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml at baseline, the 3-year cumulative incidence of prostate cancer was 0%, 0.1%, 0.3%, and 5.7%, respectively. No prostate cancer was identified in those <50 years, regardless of PSA level. CONCLUSIONS: If PSA screening is recommended, males >50 years with PSA of 3.0-3.9 ng/ml at baseline should undergo rescreening at 2 years. For men with PSA <3.0 ng/ml, PSA rescreening at intervals of ≥ 3 years is appropriate. PSA screening may not be indicated in males of <50 years of age.

Development of multichord ion Doppler spectroscopy system for toroidal flow measurement of field-reversed configuration.

A double-chord ion Doppler spectroscopy (IDS) system was developed to measure the ion temperature and flow velocity of field-reversed configuration (FRC) plasmas in the FRC amplification via a translation-collisional merging (FAT-CM) device. Adopting a Czerny-Turner mount monochromator and 16-channel photomultiplier tube array, the developed IDS system achieves high wavelength resolution and fast time response. In addition, two vertically aligned optical paths share the optical system up to the monochromator and then branch just before the detector, successfully reducing crosstalk to <1%. The Doppler broadening was measured at two measurement points in the FAT-CM device, simultaneously, and ion temperatures of ∼50 eV were measured. Toroidal spin-up from 7 to 15 km/s and a steady flow velocity of ∼10 km/s were estimated from the Doppler shift obtained by the developed system. The observation of the toroidal flow velocity and the spatial profile of the ion temperature of the FRC plasma in the FAT-CM device were realized. These spectroscopic diagnostic's double chord capabilities will aid in understanding and improving the FRC plasmas.

Development of visible light tomographic imaging system for field-reversed configuration collisional merging experiment.

A visible light tomographic imaging system has been developed for the collisional merging experiment of field-reversed configurations (FRCs) on the FRC Amplification via Translation-Collisional Merging device at Nihon University. Two FRCs formed by field-reversed theta-pinch translate at super-Alfvénic velocity and collide with each other. The translation and collision processes are completed in 20-30 µs, and a single FRC is reformed in ∼70 µs. To study these translation and collisional merging processes, the tomographic system, including fast response tomographic cameras and a reconstruction method assuming a Rigid-Rotor (RR) model, is developed. The developed tomographic cameras simply consist of 16 channels of multi-anode photomultipliers, a band-pass filter, a slit, and a cylindrical lens, which expands the viewing angle. Because the viewing angle is limited by the size of the viewports of the metal chamber, the iterative method assuming the RR model has been applied to reconstruct tomographic images from a small number of projections. The developed tomographic imaging system can estimate the behavior of FRCs. Four cameras are installed in the two cross sections near the collision point. The radial shift of each translated FRC can be calculated by this system. Details of the developed tomographic camera system and RR reconstruction method are reported.

Spectroscopic observation of super-Alfvénic field-reversed configuration merging process by mixing of tracer ions.

Visualization of the collisional merging formation process of field-reversed configuration (FRC) has been attempted. In the collisional merging formation process, two initial FRC-like plasmoids are accelerated toward each other by a magnetic pressure gradient. The relative speed of the collision reaches several times the typical ion sonic speed and Alfvénic speed. The magnetic structure of the initial-FRCs is disrupted in the collision process, but the FRC-like magnetic structure is reformed in ∼30 µs after the collision. Magnetic reconnection should occur in this process; however, general theoretical models in magnetohydrodynamics approximation cannot be applied to this process because of the high-beta nature of FRC and super-Alfvénic/sonic relative speed. In this work, the spectroscopic observation of the collisional merging FRC formation was conducted to evaluate the timescale and geometry of merging. A slight amount of tracer element (e.g., helium) was mixed into one of two initial-FRCs. Mixing of the tracer did not cause serious adverse effects on the performance of the initial-FRC in the collision and merging processes. The collision and merging processes were visualized successfully and observed using a fast-framing camera with a bandpass filter. The timescale of merging and the outflow speed in the collisional merging process of FRCs were optically evaluated for the first time.

Quantitation of human herpesvirus-6 (HHV-6) DNA in a cord blood transplant recipient with chromosomal integration of HHV-6.

Chromosomal integration of the human herpesvirus-6 (HHV-6) genome (CIHHV-6) is an important consideration if HHV-6 DNA is detected during the course of transplantation. A 4-year-old girl with refractory anemia with excess blasts type-2 was diagnosed with CIHHV-6 before a cord blood transplantation. HHV-6 DNA was serially quantitated by polymerase chain reaction assay in the transplant period. The possibility of HHV-6 reactivation in a transplant recipient with CIHHV-6 was suspected in our case.

Multi-point density measurement of a collisional merging formation process of FRCs.

Collisional merging formation of field-reversed configuration (FRC) plasmas at supersonic velocities was performed using the FRC amplification via translation-collisional merging device. Supersonic collisional merging formation is a novel technique to form an FRC that is long-lived compared to a conventional initial formation FRC; however, this technique requires measuring the plasma parameters at multiple points simultaneously because of the dynamic translation/merging process. Herein, we have developed a new interferometer and have observed the dynamic behavior of FRCs in the formation, translation, and merging processes simultaneously. In this study, as one of the performance evaluations of the developed simultaneous density measurement, collision/merging of FRCs have been conducted in the confinement section with and without background neutral gas. Comparing translation into deuterium gas vs translation into a vacuum environment prior to the collisional merging, we found that the background neutral particles were trapped in the merged FRC; moreover, a difference in the decay rate of the stored internal energy was observed.

Internal magnetic measurement in collisional-merging process of a field-reversed configuration.

An internal magnetic probe array has been developed to observe the three components of the magnetic field simultaneously in the vicinity of the collision surface of two colliding plasmoids at supersonic/Alfvénic velocity. Collisional-merging formation of a field-reversed configuration (FRC) has been conducted in the (FRC Amplification via Translation-Collisional Merging) device at Nihon University. Significant plasma heating and an increase in trapped poloidal magnetic flux have been observed during/after the collisional-merging process in the FAT-CM device. In this dynamic formation process, two FRC-like plasmoids formed by a field-reversed theta-pinch method collide in the middle of the confinement chamber at a relative speed of 200-400 km/s. Therefore, the excited shockwave is considered as one of the heating mechanisms. The developed probe array installed in the middle of the confinement chamber observes the internal structure of the magnetic field. The probe consists of 12 sets of three-axis chip inductors arranged at intervals of 40 mm. The measurement position can be varied in the radial direction. In the single translation and collisional-merging experiment, the internal magnetic probe measures the magnetic field's radial distribution with a high time resolution under noise.

Development of a Langmuir probe array for radial potential profile measurement in the collisional merging formation FRC.

The radial electric field in a field-reversed configuration (FRC) plasma plays an important role in the global stability and confinement properties. Herein, we developed a new Langmuir probe array named "Skewered probe" employed in measuring the radial potential profile in the collisional merging formation of an FRC in the FAT-CM (FRC Amplification via Translation - Collisional Merging) device. Because an FRC has a strong toroidal flow, the skewered probe consists of alternately skewered ring electrodes and ceramic beads on a thin stainless-steel tube to neutralize the effect of plasma flow. The developed array has nine electrodes, one every 2 cm from r = 9-25 cm, and it measures the FRC boundary in the case when the radius of the excluded flux ranges from 10 to 20 cm. The skewered probe also has one additional electrode that measures the potential near the chamber wall as a reference for the other electrodes. The radial potential profile of the FRC formed by the collisional merging method in the FAT-CM device was measured using the probe, and the results showed that the region of negative potential gradually changed to a positive potential after merging the FRCs. It was also shown that a strong outward electric field is formed near the separatrix at n = 2 rotational instability.

Development of a fast response neutron detector for the supersonic FRC collision process.

The collisional merging experiments of the field-reversing configuration (FRC) at supersonic/Alfvénic velocities have been performed in the FRC Amplification via Translation-Collisional Merging device only in Japan. This experiment may excite shockwaves and cause particle acceleration. To obtain supporting evidence of particle acceleration by shockwaves, we have proposed to observe neutrons originating from the D-D fusion reaction of accelerated non-thermal particles. A plastic scintillation detector has been developed for the supersonic/Alfvénic collision/merging FRC experiment. The developed neutron detector has sufficient performance of neutron sensitivity and nanosecond response time. In the collisional merging process, we obtained a signal that could be considered a neutron, which is not predicted by the adiabatic compression process in the two-dimensional magnetohydrodynamics simulation.

MHD simulation of supersonic FRC merging corrected by non-invasive magnetic measurements.

In this study, a newly developed correction method with external magnetic measurements for the magnetohydrodynamics (MHD) simulation of the collisional merging formation of a field-reversed configuration (FRC) realized the estimation of the internal structure of the FRCs without invasive internal measurements. In the collisional merging formation of FRCs, an FRC is formed via merging of two initial FRC-like plasmoids at supersonic/Alfvénic velocity. An invasive diagnostic may also interfere with the collisional merging formation process. A two-dimensional resistive MHD simulation was conducted to evaluate the global behavior and internal structure of FRCs in the collisional merging formation process without invasive measurements. This code simulated the initial formation and collisional merging processes of FRCs including discharge circuits. However, the translation velocity and the pressure of initial FRCs did not simultaneously agree with the experimental values because the magnetic pressure gradient in each formation region could not be reproduced without the artificial adjustment of the initial condition. The experimentally measured current distribution was given as the initial condition of the circuit calculation in the developed correction method. The initial FRCs were successfully translated at the translation velocity and plasma pressure in the corrected simulation, both of which were equivalent to the experiments. The properties of the merged FRCs in the experiments such as volume, total temperature, and average electron density were reproduced in the corrected simulation. The detailed radial profile of the internal magnetic field of the FRC was also measured and found to agree very well with the simulation results.

Physical vapor deposition using a coaxial ion acceleration method.

A novel physical vapor deposition method involving electromagnetic acceleration using a set of coaxial electrodes has been developed. In this study, the coaxial ion acceleration method is applied for a diamond-like carbon (DLC) thin film formation. In the developed method, the central electrode made of the deposition material is sputtered by the noble gas plasma current and accelerated toward the deposition chamber. Because the sputtered ions are accelerated by the Lorentz self-force, the ion injection energy can be controlled separately from the plasma temperature. In addition, the gaseous hydrocarbon, which is commonly used for DLC formation, is not required since a noble gas is used as the discharge gas.

Nicotine enhances skin necrosis and expression of inflammatory mediators in a rat pressure ulcer model.

BACKGROUND: Many bedridden patients develop pressure ulcers, not only in hospital but also at home. Clinical studies have indicated cigarette smoking to be a risk factor for pressure ulcers. However, the contribution of nicotine to pressure ulcer formation has not been identified. OBJECTIVES: We aimed to clarify the effect of nicotine on pressure ulcer formation, and its mechanism. METHODS: Ischaemia-reperfusion (I/R) was performed in rat dorsal skin to induce pressure ulcers. The extent of the resulting necrotic area was determined. To clarify the mechanism of the effect of nicotine, mRNA levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1beta, IL-6 and inducible nitric oxide synthase (iNOS) and protein expression of COX-2 and iNOS in the necrotic area were investigated by real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. Furthermore, the effects of the COX-2 inhibitor NS-398 and the iNOS inhibitor aminoguanidine on necrosis were examined. RESULTS: Skin necrosis in the I/R-treated area was significantly increased by intraperitoneal administration of nicotine (0.175 mg kg(-1) daily). Repeated nicotine administration had little effect on systolic and diastolic blood pressure. I/R treatment increased mRNA levels of COX-2, IL-1beta, IL-6 and iNOS, which were further augmented by nicotine in a dose-dependent manner. Correspondingly, nicotine (0.35 mg kg(-1) daily) markedly enhanced the protein expression of COX-2 and iNOS. Moreover, NS-398 and aminoguanidine showed a tendency to abrogate the increase of I/R-induced skin necrosis caused by nicotine. CONCLUSIONS: These results suggest that the increased risk of pressure ulcers due to cigarette smoking is mediated, in part, by nicotine. They also indicated that the effect of nicotine is not mediated by a change in blood pressure, but is elicited via an increase of inflammatory mediators in the I/R-treated skin.