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Introduction: The peribiliary gland is an accessory bile duct gland. Hyperplasia of these tissues may lead to elevation of the mucosa in the bile ducts and bile duct stenosis. We herein report a case of peribiliary gland hyperplasia that required preoperative differentiation from bile duct cancer, with a discussion of the literature. Case Presentation: The patient had an adenomatous lesion in the ascending colon that was difficult to treat endoscopically; therefore, surgery was planned. Preoperative abdominal ultrasonography revealed a bile duct tumor, and endoscopic ultrasonography revealed a mass lesion around the confluence of the cystic duct. Computed tomography revealed localized wall thickening in the middle bile duct, and the upstream bile ducts were slightly dilated. In addition, continuous thickening of the bile duct wall from the gallbladder to the confluence of the cystic duct was observed. No distant metastases, such as liver metastases, or nearby enlarged lymph nodes were observed. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed a papillary-like elevated lesion in the bile duct near the confluence of the cystic duct, and a biopsy and bile cytology from the same area showed no malignant findings. As a result, the possibility that the patient had gallbladder or bile duct cancer could not be ruled out; therefore, a policy of surgery together with the ascending colon tumor was decided after receiving sufficient informed consent. During surgery, the patient underwent extrahepatic bile duct resection, reconstruction of the biliary tract using the Roux-en-Y method, and right hemicolectomy. Both duodenal and hilar bile duct transects were subjected to a fast frozen section analysis during surgery, and the results were negative for cancer. A histopathological examination of the resected specimen revealed no malignant findings in the bile duct lesions, and a diagnosis of peribiliary gland hyperplasia with chronic inflammatory cell infiltration and fibrosis of the extrahepatic bile duct wall was made. Conclusions: We encountered a case of peribiliary gland hyperplasia that was difficult to distinguish from bile duct cancer.

Abstract:: Technique: The Endoscopic Mini- or Less-open Sublay operation (EMILOS) is a transhernial repair that allows endoscopic dissection and mesh placement in the retrorectus/retromuscular space, and simultaneous transversus abdominis release (TAR) for larger hernias. The operative summary is as follows. 1 A 7-cm longitudinal skin incision was made immediately above the hernial orifice. 2 The hernial sac was circumferentially dissected to the border of the defect, and the abdomen was opened. 3 The posterior rectus sheath (PRS) was incised approximately 5 mm lateral to the medial border of the rectus sheath to enter the retrorectus space. 4 Exploratory laparoscopy was performed, and the peritoneum was closed. 5 A single port platform was attached to the wound, and the abdominal wall was insufflated. The retrorectal space was dissected laterally to the outer edge of the rectus abdominis muscle. The linea alba was incised at least 5 cm cranially and caudally from the border of the hernia defect to obtain sufficient mesh overlap. 6 The TAR was added to the left side to facilitate medial advancement of the PRS. (7) The PRS was approximated with continuous suture. A self-gripping mesh was trimmed and implanted in the retrorectus space. The mesh was secured with 3-0 absorbable sutures (8) A closed-suction drain was placed on the mesh, and the wound was trimmed and closed. Results: The postoperative course was uneventful. No recurrence was observed at 6-month follow-up. Conclusions: This technique may be advantageous because it allows minimal skin incision with physiological reconstruction of abdominal wall.

Objectives: Malnutrition is associated with an increased risk of hospital readmission for heart failure in patients with acute decompensated heart failure (ADHF). Therefore, evaluation of the nutritional status in patients with ADHF may be important. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are widely used objective indexes for evaluation of the nutritional status. The present study was performed to determine the best nutritional index for predicting the prognosis in older adults with ADHF. Methods: We retrospectively studied 167 older adults (>65 years of age) who were admitted with ADHF from January 2012 to December 2015 and discharged alive. The objective nutritional status was evaluated using the GNRI, CONUT score, and PNI at admission. The endpoint of this study was unplanned hospitalization for worsening heart failure (WHF) within 1 year after discharge. Results: During the follow-up period, 58 patients were readmitted for WHF. In the multivariate Cox analysis, only the GNRI (p

Abstract Aims This study aimed to determine the new cut‐off value of serum angiotensin‐converting enzyme (ACE) levels for detecting patients with sarcoidosis and to examine the change in ACE levels after the initiation of immunosuppressive therapy. Methods and results We retrospectively examined patients in whom serum ACE levels were measured for suspected sarcoidosis between 2009 and 2020 in our institution. For patients diagnosed with sarcoidosis, changes in ACE levels were also observed. Of the 3781 patients (51.1% men, 60.1 ± 17.0 years old), 477 were excluded for taking ACE inhibitors and/or immunosuppression agents or those with any diseases affecting serum ACE levels. In 3304 patients including 215 with sarcoidosis, serum ACE levels were 19.6 IU/L [interquartile range, 15.1–31.5] in patients with sarcoidosis and 10.7 [8.4–16.5] in those without sarcoidosis (P

In the design of ultralow leakage devices such as image sensors, it is necessary to understand the influence of low-density defects during plasma processing—plasma-induced physical damage (PPD)—on device performance. Defects created by plasma exposure act as carrier conduction sites and induce an increase in leakage (e.g., dark) current. This study proposes a PPD evaluation scheme for low-density defect assessments, specifically defects created in the lateral direction due to lateral stochastic straggling (lateral PPD). Two test structures were designed: a single device with a leakage current ( ${I} _{\mathrm{ leak}}$ ) and a complementary metal-oxide-semiconductor image sensor (CIS) circuit with a dark current ( ${I} _{\mathrm{ dark}}$ ). The energy level and density of defects distributed in the lateral direction were estimated using the Shockley–Read–Hall (SRH) model. The energy level ( ${E} _{\mathrm{ t}}$ ) was derived using the SRH model from the temperature dependence of ${I} _{\mathrm{ leak}}$ and ${I} _{\mathrm{ dark}}$ defined as the activation energy ${E} _{\mathrm{ a}}$ . The trap density ( ${N} _{\mathrm{ t}}$ ) was also determined. A comprehensive comparison of these parameters was conducted. Both ${I} _{\mathrm{ leak}}$ and ${I} _{\mathrm{ dark}}$ are dependent on the contact opening diameter after plasma exposure, which implies the presence of defects in the lateral direction via lateral PPD. From the analysis of the temperature dependence of ${I} _{\mathrm{ leak}}$ and ${I} _{\mathrm{ dark}}$ , the lateral PPD influenced the mean value of ${E} _{\mathrm{ a}}$ . Moreover, we confirmed that an increase in ${I} _{\mathrm{ dark}}$ indicates an increase in the number of trap sites, and more specifically, an increase in defects at shallow levels. The derived trap site density in the CIS circuit was consistent with that of a single device. The proposed evaluation scheme is useful for PPD evaluation in the presence of low-density defects, and is critical for the design of future low-leakage devices.

Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs.

The acetabular labrum enhances hip joint stability and plays a key role in osteoarthritis (OA) progression. Labral nerve endings contribute to hip OA pain. Moreover, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are associated with pain. Consequently, we analysed VEGF and NGF expression levels in the labrum and their roles in OA. Labra obtained from OA patients were stained immunohistochemically, and labral cells were cultured and subjected to a reverse transcription (RT)–polymerase chain reaction (PCR) to analyse VEGF and NGF mRNA expression. VEGF and NGF expression were compared in each region of the labrum. Correlations between VEGF and NGF expression and age, body mass index, Kellgren–Lawrence grade, Harris Hip Score, the visual analogue scale (VAS), and Krenn score were analysed, and the RT-PCR confirmed the findings. VEGF and NGF expression were high on the labral articular side, negatively correlated with the Krenn score, and positively correlated with the VAS in early OA. VEGF and NGF mRNA expression increased significantly in patients with severe pain and decreased significantly in severely degenerated labra. In early OA, VEGF and NGF expression in the acetabular labrum was associated with the occurrence of hip pain; therefore, these factors could be effective targets for pain management.

People with speech impediments and hearing impairments, whether congenital or acquired, often encounter difficulty in speaking. Therefore, to acquire conversational communication abilities, it is necessary to practice lipreading and imitation so that correct vocalization can be achieved. In conventional lipreading methods using machine learning, model refinement and multimodal processing are the norm to maintain high accuracy. However, since 3D point clouds can now be obtained using smartphones and other devices, it is becoming viable to consider methods that use 3D information. Therefore, given the obvious relation between vowel pronunciation and three-dimensional (3D) lip shape, in this study, we propose a method of extracting and discriminating vowel features via deep learning using 3D point clouds of the lip region. For training, we created two datasets: mixed-gender and male-only datasets. The results of the experiment showed that the average accuracy rate of the k-fold cross-validation exceeded 70% for both the mixed-gender and male-only data. In particular, although the proposed method was ~3.835% less accurate than the machine learning results for 2D images, the training parameters were reduced by 92.834%, and the proposed method succeeded in obtaining vowel features from 3D lip shapes.

In the previous reports, a methodology for estimating noise radiation including airborne noise from a mechanical system under the operational condition by component test of a certain active subsystem using the in-situ blocked force approach, which is normally used for estimating only structure borne noise, was proposed and verified by numerical simulations of noise radiation from a cantilever rectangular plate. This paper describes experimental verification of the proposed methodology by application to rattle noise from a column type electric power steering system (EPS) for a vehicle. Therefore an EPS corresponds to the active subsystem and the other parts such as vehicle body correspond to passive subsystems. At first, a method of measuring rattle noise from an EPS under the operational conditions, i.e., running tests with a vehicle, was established. Since it is possible to apply the in-situ blocked force approach also to vehicle running tests and to estimate rattle noise, the measured and estimated rattle noises under an identical operational condition were compared and validity of the proposed methodology was confirmed. Next, a component test bench which enables to reproduce vibration behavior of an EPS under the operational conditions was developed, and rattle noise under an operational condition was estimated by means of the proposed methodology using both vibration accelerations measured with this component test bench and vibro-acoustic transfer functions measured with the vehicle under a static condition. Finally, the proposed methodology was verified by comparing the estimated and measured rattle noises under the operational condition. The proposed methodology is expected to replace time-consuming operational tests of a whole mechanical system to simple component tests of the active subsystem.

It is important to secure food safety. If a packaged food can be sterilized, food poisoning can be reduced considerably because the packaged food in a plastic container is useful to prevent attaching microorganisms. However, a fresh food, e.g., a salad or sashimi, cannot be sterilized by thermal sterilization. Therefore, we are studying sterilization methods for packaged fresh foods, such as packed salads. In this study, we have investigated the applicable probability of the sterilization method using cold plasma applied to the packaged fresh food. Especially, we have investigated the probability of the sterilization of microorganisms living in a small hollow between the overlapped fresh foods. A plastic petri dish with a lid was used for simulating the plastic container. The cold plasma was applied into the petri dish by a barrier discharge generated by a pulsed voltage. E. coli was used for a target of sterilization. The E. coli was set on a culture agar medium instead of the salad. The experimental results showed that the sterilization method combining the plastic film and cold plasma of the barrier discharge generated by the pulsed voltage is applicable to sterilize microorganisms living in the hollow between the overlapped fresh foods for the packaged fresh food.

The in-situ blocked force approach is suitable for estimating noise radiation from a mechanical system by component tests of its active subsystem because blocked force is a specific characteristic of the active subsystem and independent from the passive subsystem or supporting structure of the component test bench for the active subsystem. However, it is reported that the in-situ blocked force approach is a methodology for estimating structure borne noise and cannot be applied to airborne noise. In this research it was found that the in-situ blocked force approach can be approximately applied to airborne noise in eigenfrequencies of the mechanical system. Therefore it was proposed to employ the in-situ blocked force approach to estimate airborne noise as an approximate method at eigenfrequencies of the mechanical system in the previous paper. In this paper the proposed estimation method was verified by numerical analysis of noise radiation from a cantilever rectangular plate. Eigenfrequencies and vibration responses of the cantilever rectangular plate were obtained by FEM and sound pressures at an observed point were calculated on the assumption that point sound sources are distributed at the all FE nodes on the whole plate surface. Furthermore, a means based on discarding small singular values in the inverse matrix method was proposed in order to reduce the estimation error which is increased in the peak frequencies of blocked forces.

We herein describe a cobalt/Xantphos-catalyzed regioselective addition of simple alkenes to acetophenone derivatives, affording branched homoallylic alcohols in high yields with perfect branch selectivities. The intermediate of the reaction would be a nucleophilic allylcobalt(I) species generated via cleavage of the low reactive allylic C(sp3)–H bond of simple terminal alkenes.

Safety assessments of nuclear plants against tsunamis have been reviewed after the Fukushima Daiichi nuclear disaster caused by a tsunami during the Great East Japan Earthquake in March 2011. These assessments are required for the restarting of operations at nuclear plants. Integrity evaluations of nuclear plant facilities at impact of floating debris caused by a tsunami are performed on the basis of the estimated strain on a facility caused by the impact force. In this paper, drop impact tests were carried out using real scale specimens of a delivery pipe and a power supply unit that nuclear plant facilities comprise. A 1500-kg power supply unit impacted on a delivery pipe (318-mm in diameter, 5-m in length) under two impact speed conditions of 5.2 and 9.5 m/s. No noticeable penetration damage to the pipe was detected under either condition. Simulated results considering strain rate dependence and constitutive equations with power hardening law showed good agreement with the experimental results. This simulation model is effective to analyze the safety margin of apparatuses at impact.

Summary Background Factor XII (FXII) deficiency and autoantibodies that bind to FXII (anti-FXII) have been described in patients with adverse pregnancy outcomes, including recurrent pregnancy loss. It has been reported that FXII functions not only as a coagulation protein but also as a growth factor. Objectives We studied the association between anti-FXII and the epidermal growth factor (EGF) system in patients with recurrent pregnancy loss. Patients/Methods We used synthetic peptides that span the second EGF-like domain in the heavy chain of FXII (EGF2) in inhibition and direct binding studies to determine if anti-FXII antibodies recognize EGF2. Furthermore, we examined whether anti-FXII antibodies, which recognize EGF2, also recognize recombinant EGF and heparin-binding EGF-like growth factor (HB-EGF). Results Among 100 patients with recurrent pregnancy loss, the plasma of 23 patients (23.0%) recognized the synthetic peptide ASQ41, which covers EGF2. Among the 23 anti-ASQ41-positive patients, plasma samples from 13 patients (56.5%) recognized the 22-residue segment C-terminal half of ASQ41. Among the 23 anti-ASQ41-positive patients, the plasma of 17 patients (73.9%) recognized recombinant human EGF. Affinity-purified anti-FXII antibodies, which recognize ASQ41, also recognized recombinant EGF family proteins such as EGF and HB-EGF. Conclusions The autoantibodies in patients with recurrent pregnancy loss recognized the EGF2 domain in FXII and other proteins of the EGF family. Since proteins in the EGF family play an important role in normal pregnancy, autoantibody-associated disruption of the EGF system may cause pregnancy loss.

This study focuses on the problem of eye irritation when measuring steady-state visual evoked potentials (SSVEPs) using a brain–computer interface and aims to clarify experimentally visual stimulus signals that do not cause discomfort to users. To this end, a method is proposed that introduces a flash stimulus in which the color is changed by changing its hue. This reduces the change in brightness while providing a color change, thereby facilitating visual stimulation with less discomfort. In experiments conducted, flash stimuli of the primary colors red, green, and blue and colors with different hues of 5–45° from these primary colors were generated to investigate the algorithm accuracy of SSVEP and discomfort. Subjective questionnaire and CFF values, which are ophthalmic parameters, were obtained for the subjects and compared to the discrimination rate. As a result of the comparison, it was confirmed that the fatigue level of the visual stimulus generated by the proposed hue change was lower than that of the conventional black-and-white stimulus. It was also confirmed that the combination of the hue difference and frequency could obtain the same discrimination rate as the conventional method.

Background: Approximately one-third of the patients undergoing cardiovascular surgery reportedly experience paroxysmal atrial fibrillation (AF) during the postoperative period. However, the usefulness of antiarrhythmic drugs for preventing postoperative AF recurrence in the Japanese population has not been extensively studied. Methods: From a total of 118 patients who developed postoperative paroxysmal AF between April 2009 and March 2011, 72 patients (45 men, mean age 68±8 years) requiring treatment for postoperative AF due to symptoms lasting ≥30 min were enrolled to prospectively investigate the efficacy of oral bepridil (100 mg/day, n=37) or aprindine (40 mg/day, n=35). Result: The AF recurrence-free survival rates at 1, 3, 7, and 14 days were 100%, 94%, 57%, and 49%, respectively, in the aprindine group, and 100%, 97%, 86%, and 76%, respectively, in the bepridil group (P=0.028, aprindine vs. bepridil). Conclusion: Bepridil, at a fixed dose of 100 mg/day, was considered to be more effective than a routine dose of aprindine for the prevention of postoperative AF recurrence.

This article discusses the photoinduced charge transfer (CT) kinetics within the reaction center complex of photosystem II (PSII RC). The PSII RC exhibits a structural symmetry in its arrangement of pigments forming two prominent branches, D1 and D2. Despite this symmetry, the CT has been observed to occur exclusively in the D1 branch. The mechanism to realize such functional asymmetry is yet to be understood. To approach this matter, we applied the theoretical tight-binding model of pigment excitations and simulated CT dynamics based upon the framework of an open quantum system. This simulation used a recently developed method of computation based on the quasi-adiabatic propagator path integral. A quantum CT state is found to be dynamically active when its site energy is resonant with the exciton energies of the PSII RC, regardless of the excitonic landscape we utilized. Through our investigation, it was found that the relative displacement between the local molecular energy levels of pigments can play a crucial role in realizing this resonance and therefore greatly affects the CT asymmetry in the PSII RC. Using this mechanism phenomenologically, we demonstrate that a near 100-to-1 ratio of reduction between the pheophytins in the D1 and D2 branches can be realized at both 77 K and 300 K. Our results indicate that the chlorophyll Chl D 1 is the most active precursor of the primary charge separation in the D1 branch and that the reduction of the pheophytins can occur within pico-seconds. Additionally, a broad resonance of the active CT state implies that a large static disorder observed in the CT state originates in the fluctuations of the relative displacements between the local molecular energy levels of the pigments in the PSII RC.

This paper proposes a methodology for estimating airborne noise from a mechanical system under the operational conditions by component tests of a certain active subsystem which is a part of the mechanical system and includes all of vibration sources in the mechanical system. The mechanical system consists of the active and passive subsystems, and supporting structure of the active subsystem is different from that under the component test conditions. Hence airborne noise from the active system under these two conditions are different from each other. Therefore the in-situ blocked force approach is expected to estimate airborne noise under the operational conditions by the component tests, because blocked force is a specific characteristic of the active subsystem and independent from its supporting structure. However it is reported that the in-situ blocked force approach is suitable for estimating structure borne noise and cannot be applied to airborne noise, it has been found that the in-situ blocked force approach can be approximately applied to airborne noise in resonant frequency of the mechanical system. This paper describes theoretical derivation of the approximation error caused by applying the in-situ blocked force approach to airborne noise. Furthermore, the error is evaluated by means of a 3-DOF simple model.

Jun Iwamoto1, Yoshihiro Sato2, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, JapanAbstract: The purpose of the study was to confirm the short-term outcome of conservative treatment in terms of the ability to return to play and factors influencing return to play in athletes with symptomatic lumbar disc herniation. A total of 100 consecutive athletes (72 male and 28 female) who consulted our sports medicine clinic during the 16-year period between September 1993 and October 2009 because of severe low back pain and/or leg pain/numbness due to lumbar disc herniation were studied. The mean age of the subjects was 23 years. All of them were conservatively treated by being advised to discontinue their sporting activities with/without short-term medication. After the subjective symptoms had reduced by more than 80%, individual training was started in order to allow the athletes to return to play. Seventy-nine athletes (79.0%) returned to play at an average of 4.8 months (range 1–12 months) after the start of treatment and were able to sustain the activities for at least 6 months, the minimum duration of follow-up in the study. The outcome of the conservative treatment was not influenced by the intensity of the sporting activity. Multiple logistic regression analyses showed that the severity of the symptoms prior to the start of treatment was the factor influencing the ability of the athletes to return to play. The present study confirmed the satisfactory short-term outcome of conservative treatment in athletes with symptomatic lumbar disc herniation regarding return to play and revealed that subjective symptoms prior to the start of treatment appeared to be a key factor in return to play after conservative treatment.Keywords: lumbar disc herniation, athletes, return to play, conservative treatment, sciatica, low back pain

Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: A retrospective study was performed to evaluate the outcome of alendronate (ALN) treatment for seven years in postmenopausal Japanese women with osteoporosis. Forty-seven postmenopausal women with osteoporosis (mean age at baseline 65.7 years) treated with ALN for over seven years in our outpatient clinic were analyzed. Lumbar spine bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) were monitored during the seven-year treatment period. Urinary NTX and serum ALP levels decreased (-48.2% at three months and -15.7% at seven years, respectively) and lumbar spine BMD increased (+12.8% at seven years) compared with baseline values. No serious adverse events were observed, including osteonecrosis of jaw, atypical femoral diaphysis fractures, or atrial fibrillation. To our knowledge, this is the first report of the outcome of ALN treatment for seven years in Japanese patients with osteoporosis. ALN successfully suppressed bone turnover and increased lumbar spine BMD from the baseline value over the course of the seven-year treatment period without causing any severe adverse events.Keywords: alendronate, osteoporosis, long-term treatment, bone mineral density, bone turnover

Jun Iwamoto1, Atsushi Miyata2, Yoshihiro Sato3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Internal Medicine, Yahata Clinic, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanAbstract: A retrospective study was conducted to evaluate the outcome of treatment with alendronate (ALN) for 5 years in postmenopausal Japanese women with an increased risk of fractures. Forty postmenopausal Japanese women with osteoporosis or osteopenia and clinical risk factors for fractures (mean age: 75.4 years) were analyzed; 33 patients were treated with alendronate and 7 were treated with alfacalcidol (ALF, controls) in an outpatient clinic run by general practitioners. The metacarpal bone mineral density (BMD) measured using a computed X-ray densitometer, urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP) were monitored during the 5-year treatment period. The urinary NTX and serum ALP levels decreased significantly in the ALN group, compared with the ALF group. The metacarpal BMD was sustained in the ALN group but decreased significantly in the ALF group; the difference between these two groups was also significant. The present study evaluated the outcome of treatment with ALN for 5 years in postmenopausal Japanese women with osteoporosis or osteopenia and clinical risk factors for fractures. ALN successfully suppressed bone turnover and sustained the metacarpal BMD over the 5-year period of treatment in postmenopausal Japanese women with an increased risk of fractures.Keywords: alendronate, osteoporosis, osteopenia, risk factors for fractures, postmenopausal women

Jun Iwamoto1, Mitsuyoshi Uzawa2, Yoshihiro Sato3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, Japan Abstract: The antiresorptive drug elcatonin (ECT) is known to relieve pain in postmenopausal women with osteoporosis. A prospective open-labeled trial was conducted to compare the effects of short-term combined treatment with alendronate (ALN) and ECT on bone mineral density (BMD) and bone turnover with those of single treatment with ALN in postmenopausal women with osteoporosis. Two hundred and five postmenopausal osteoporotic women (mean age: 70 years) were recruited in our outpatient clinic. Forty-six women with back pain were treated with ALN and ECT (intramuscular, 20 units a week), and 159 women without obvious back pain were treated with ALN alone. The lumbar BMD, urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP) were measured during the six-month treatment period. The baseline characteristics, except for age, body weight and number of patients with prevalent vertebral fractures, were not significantly different between the two groups. The mean increase rate in the lumbar BMD at six months was similar in the ALN (+4.41%) and ALN+ECT (+5.15%) groups, following similar reduction rates in urinary NTX levels (-40.2% and -43.0%, respectively, at three months) and serum ALP levels (-19.0% and -19.7%, respectively, at six months). These results were consistent even after adjustments for age, body weight, and number of patients with prevalent vertebral fractures. The present study in postmenopausal osteoporotic women confirmed that the effects of short-term combined treatment with ALN and ECT on lumbar BMD and bone turnover in patients with back pain appeared to be comparable to those of single treatment with ALN in patients without obvious back pain.Keywords: alendronate, elcatonin, osteoporosis, postmenopausal women, back pain

Aim and method: There have been few reports about the risk of ischemic stroke in elderly patients with non-valvular paroxysmal atrial fibrillation (NVPAF). The aim of this study was to evaluate the validity of the guidelines issued by the Japanese Circulation Society to prevent ischemic stroke for NVPAF in patients without a high risk of ischemic stroke. The risk evaluation was made based on the CHADS2 Score. However, we excluded age in this study, but included coronary disease. This study investigated a total of 150 patients with paroxysmal atrial fibrillation (AF) who did not have a high risk of stroke (117 men and 33 women, mean age 68 ± 12 years). The patients were divided into three groups according to age: the patients who were less than 60 years old (Group I, N = 58, Antithrombic therapy (+) = 18), those who were between 60 and 75 years old (Group II, N = 68, Antithrombic therapy (+) = 36) and those who were more than 75 years old (Group III, N = 24, Antithrombic therapy (+) = 7). The annual rates of thromboembolism among three groups were retrospectively analyzed. The mean follow-up periods were 56 ± 37 months. Results: (1) The annual rate of thromboembolism in Group III (4.0%) was significantly higher than in Group I (1.4%) and Group II (1.8%) (P < 0:05). (2) The annual rates of thromboembolism in patients without antithrombotic therapy were 2.1% in Group I, 1.3% in Group II and 3.9% in Group III. The annual rate was significantly lower in Group II than in Group III (P < 0:05). (3) The annual rates of thromboembolism with aspirin treatment (80- 100 mg/day) were 0% in Group I, 3.0% in Group II and 8.4% in Group III. There was a significant difference in the annual rate among the three groups (P < 0:05). (4) The annual rate of thromboembolism in patients with warfarin treatment was 0% in Group I, 1.5% in Group II and 0% in Group III (P = NS among 3 groups). Conclusion: Antithrombic therapy is required in elderly patients with NVPAF to prevent ischemic stroke. Antithrombic therapy with Warfarin, but not aspirin, reduces ischemic stroke in patients with NVPAF regardless of their age.

Jun Iwamoto1, Yoshihiro Sato2, Tsuyoshi Takeda1, Hideo Matsumoto21Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, JapanAbstract: Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. In particular, hip fractures are an important cause of mortality and morbidity among postmenopausal women. Anti-resorptive therapies that produce greater decreases in bone turnover markers together with greater increases in bone mineral density (BMD) are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Thus, treatment with potent anti-resorptive drugs like alendronate is a strategy for preventing hip fractures in postmenopausal women with osteoporosis. The purpose of this paper is to discuss the efficacy of alendronate against hip fractures and the mechanism for this anti-fracture efficacy in postmenopausal women with osteoporosis. A meta-analysis of randomized controlled trials has shown that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis. According to the analyses of the Fracture Intervention Trial, each 1 standard deviation reduction in a 1-year change in bone-specific alkaline phosphatase (BSAP) is associated with 39% fewer hip fractures in alendronate-treated postmenopausal women, and those with at least 30% reduction in BSAP have a 74% lower risk of hip fractures relative to those with less than 30%. Alendronate is effective in reducing the risk of hip fractures across a spectrum of ages. The mechanism for this anti-fracture efficacy has been clarified; alendronate strongly suppresses bone turnover and subsequently increases hip BMD, decreases cortical porosity, improves parameters of hip structure geometry (cortical thickness, cross-sectional area, section modulus, and buckling ratio), and produces more uniform mineralization (increases the mean degree of mineralization of bone) in cortical bone. A once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment than the once-daily dosing regimen, leading to greater efficacy against hip fractures. Thus, the efficacy of alendronate against hip fractures has been confirmed in postmenopausal women with osteoporosis, especially with a once-weekly dosing regimen.Keywords: hip fracture, bone turnover, bone mineral density, cortical porosity, cortical thickness

Objective: To investigate the long-term effects of combination therapy with antiarrhythmic agents and pravastatin (10 mg/day) in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation (AF) and hyperlipidemia. Method and Results: In all, 318 patients (mean age: 69 ± 12 years) with paroxysmal AF were divided into 2 groups, one receiving pravastatin for hyperlipidemia (pravastatin (+) group, N = 41) and the other not (pravastatin (−) group, N = 277). At 60 months, the survival rate for patients free from conversion to permanent AF was significantly greater in the pravastatin (+) group than in the pravastatin (−) group. The percentage of patients who eventually developed permanent AF despite anti-arrhythmic therapy was significantly lower in the pravastatin (+) group than in the pravastatin (−) group (9.8% vs. 25.3%). Left atrial dimensions were significantly increased in the pravastatin (−) group during the follow-up period (from 34.8 ± 6.6 mm to 37.6 ± 7.0 mm: p < 0.01). In contrast, in the pravastatin (+) group, left atrial dimensions remained unchanged between baseline and after treatment (34.4 ± 7.3 mm vs 35.5 ± 6.6 mm). Conclusion: In patients with paroxysmal AF and hyperlipidemia, addition of pravastatin to anti-arrhythmic agents seems to enhance the efficacy of these agents in maintaining sinus rhythm and preventing the development of structural remodeling in the myocardium.

When the recording density of an optical disc increases, allowable tilt angle between the optical disc and the objective lens decreases. An objective lens actuator for an optical disc drive which is a kind of information processing equipments is needed to have little tilting action when it moves the objective lens in the focusing and tracking directions. We developed a new objective lens actuator with two configurations to reduce the rolling moment generated in the focusing coils and in the tracking coils of the actuator. One configuration is an arrangement in which the tracking coils and magnets at one side of the actuator are arranged reverse to those at the other side. In this configuration, magnetic flux density affecting the tracking coils at one side of a holder holding the objective lens increases at one side of the tracking coils, and magnetic flux density affecting the tracking coils at the other side of the holder increases at the other side of the tracking coils. The other configuration has an inner magnet placed inside the focusing coil. In the second configuration, the inner magnets produce magnetic flux density in the tracking direction affecting the focusing coils in addition to magnetic flux density by the magnets. This actuator cancels the deviation of magnetic flux density when it moves the objective lens in the focusing and tracking directions, and therefore the rolling moment is reduced. Experimental results show that the tilt angles of the developed actuator applying electric current to the tracking coils and to the focusing coils are reduced to 20% and 10%, respectively, of the values for a conventional actuator.

The aim of the present study was to examine the influence of gastrectomy (GX) on cortical and cancellous bones in rats. Twenty male Sprague-Dawley rats were randomized into the two groups of 10 animals each: a sham operation (control) group and a GX group. Seven weeks after surgery, the bone mineral content and density (BMC and BMD, resp.) and the mechanical strength of the femur were determined, and bone histomorphometric analyses were performed on the tibia. GX induced decreases in the BMC, BMD, ultimate force, work to failure, and stiffness of the femoral distal metaphysis and the BMC, BMD, and ultimate force of the femoral diaphysis. GX induced a decrease in cancellous bone mass, characterized by an increased osteoid thickness, osteoid surface, osteoid volume, and bone formation. GX also induced a decrease in cortical bone mass, characterized by increased endocortical bone resorption. The GX induced reductions in the bone mass and strength parameters were greater in cancellous bone than in cortical bone. The present study showed that the response of bone formation, resorption, and osteoid parameters to GX and the degree of GX-induced osteopenia and the deterioration of bone strength appeared to differ between cortical and cancellous bones in rats.

Obtaining viable islets is a crucial step for successful islet transplantation. Adenosine triphosphate (ATP) is a marker of cell viability. However, little is known about any changes in the energy status of the tissues that are being digested during the digestion phase. We herein examined whether the ATP content in serially digested pancreatic tissue samples could be specific objective parameters that signal the optimal point to stop the digestion process. We obtained partial pancreata (body to tail) from 4- to 5-year-old pigs from a slaughterhouse. The tissue samples were preserved in M-Kyoto solution for less than 3 h. They were digested using an automated enzymatic and mechanical dissociation system at 37°C for 90 min following intraductal injection of Liberase HI. Samples were collected from the digestive circuit every 5 or 10 min to determine the ATP level, total adenine nucleotide (TAN) level, islet count (count/g), and yield of islet equivalent (IEQ) in the serial digestive fluids. The ATP and TAN levels, IEQ and islet count were increased and then decreased during digestion process. The profile of these parameters differed from case to case. However, when ATP changing ratio (respective value/precedent value) was compared with IEQ changing ratio, a greater than threefold increase in the ATP changing ratio followed by an increase in the islet count changing ratio within 5 min was consistently observed, indicating the optimal time to stop the digestion. The ATP levels of the handpicked islets in the digested samples were lower in the overdigested phase in comparison to those in the earlier digested phase. These results indicate that the ATP level in digested fluid could be an effective indicator to estimate the viability of cells as well as determine the optimal time to terminate the digestion process in order to obtain viable islets.

The purpose of the present study was to determine the associations of age and history of non- and low-traumatic fractures with the severity of abdominal aortic calcification in Japanese postmenopausal women and men. Four hundred and one Japanese persons (24 men and 377 postmenopausal women, mean age: 73.8 years) for whom thoracic and lumbar spine radiographs had been obtained to evaluate their posture prior to patient participation in a fall-prevention exercise program were enrolled. The associations of sex, age, history of hip fracture, prevalence of vertebral fracture, and spondylosis grade (the Nathan degree) with the severity of abdominal aortic calcification (length of calcification, as evaluated according to the number of vertebral bodies) were analyzed. Nine subjects (2.2%) had a history of hip fracture, and 221 (55.1%) had at least one prevalent vertebral fracture. Two hundred and sixty-seven subjects (66.6%) had first-degree spondylosis. Age and the number of prevalent vertebral fractures, but not sex, history of hip fracture, or spondylosis grade, were significantly associated with the severity of abdominal aortic calcification. The present study confirmed that age and the number of vertebral fractures were associated with the severity of abdominal aortic calcification in Japanese postmenopausal women and men.

One of the goals of islet transplantation is to transplant viable islets without host immunosuppression. The present study was designed to determine whether pretreatment of islets with mitomycin-C (MMC) followed by culture enhances islet survival in a rat-to-mouse xenogeneic combination. WS(RT1k) rat islets pretreated with various concentrations of MMC (0, 3.2, 10, 32, 100, 320, and 1000 μg/ml) were tested for viability by in vitro insulin secretory capacity and vital staining of islets. The MMC-treated islets (10 μg/ml) cultured for various periods (4, 20, or 40 h, 3 or 7 days) were transplanted into the renal subcapsular space of STZ-induced diabetic C57BL/6 (B6: H-2b) mice. MMC-treated or nontreated islets were subjected to microarray gene analysis and immunohistological study. Evaluation of in vitro insulin secretory capacity and vital staining of islets indicated that MMC at a dose ≤32 μg/ml is nontoxic and preserves islet function. Marked prolongation of graft survival was noted with half of islet grafts surviving indefinitely (>100 days) when 10 μg/ml of MMC-treated islets was transplanted after 40 h or 3 days in culture, but not when they were transplanted within 4 h following treatment or at 7 days following treatment, indicating that there is a critical culture period necessary for successful islet graft survival. Microarray analysis suggested possible genes for this prolongation with TGF-β highly expressed in MMC-treated islets subjected to culture for 3 days. Our results indicate that MMC treatment followed by a critical culture period induces marked prolongation of rat islet xenograft survival in nonimmunosuppressed recipient mice, offering a strategy for islet transplantation without immunosuppression.

We have previously shown that mitomycin C (MMC) treatment of donor tissue resulted in significant prolongation of graft survival in allo- and xenotransplantation models. However, the mechanisms involved in this prolongation are not clearly understood. This study aims to shed light on the immune responses to MMC-treated islet xenografting under the kidney capsule. Collagenase-digested WS (RT1 k ) rat islets incubated for 30 min with MMC and subsequently cultured for 20 h were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (B6;H-2 b ) mice. The grafts were harvested on postgrafting day 7 and sections were prepared and stained by hematoxylin and eosin (H&E). Histological study of the grafts in a group not treated with MMC showed marked cellular infiltration and destruction of islet clusters, whereas that of MMC-treated grafts demonstrated a bleb formation under the kidney capsule, in which islet cell clusters were reorganized, creating a layer of cells fixed to the interior of the bleb. Minimal invasion by inflammatory cells was observed only at the edge of the bleb, and most islet cells were protected from these infiltrating cells. In conclusion, MMC treatment induces remodeling of islet structure and forms a bleb under the kidney capsule, where no inflammatory cell infiltration occurs, suggesting that this site is a kind of immunologically privileged environment for xenografted islets.

Background: Neurofibromatosis type 1 (NF-1) is often characterized by vascular disorders related to vessel vulnerability that can lead to unfavorable outcomes. Here, we describe a case of NF-1 complicated with a massive subcutaneous hematoma posing a risk of visual impairment for which rapid decompression and a subsequent less invasive approach result in a favorable outcome. Case Description: A 40-year-old woman with NF-1 presented with a massive left subcutaneous temporal hematoma following a mild head contusion. Four days after hospitalization, the hematoma increased in size and severely compressed the left eye, prompting immediate hematoma removal to preserve visual function. Immediately after the hematoma removal, a superficial temporal arteriovenous fistula was found on the digital subtraction angiography and embolized by the endovascular procedure. Her visual acuity was preserved, and no bleeding recurrence was observed throughout the follow-up. Conclusion: Surgical hematoma removal followed by endovascular treatment was effective in preserving visual function. Since vessel fragility is characteristic of patients with NF-1, it should be kept in mind that vascular complications may lead to serious clinical outcomes. In certain NF-1 cases, less invasive treatments for vascular abnormalities may be preferable. [ABSTRACT FROM AUTHOR]