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Background: Dolichoectasia is a rare arterial condition characterized by the dilatation, tortuosity, and elongation of cerebral blood vessels. The vertebrobasilar artery and internal carotid artery are the common sites of dolichoectasia. However, dolichoectasia of the branch arteries, such as the ophthalmic artery (OA), is extremely rare. To the best of our knowledge, this is the first case of ophthalmic dolichoectasia that was successfully treated with endovascular internal coil trapping., Case Presentation: A 54-year-old female patient presented with transient left ophthalmalgia and visual disturbance. Magnetic resonance imaging revealed a dilated and elongated left OA compressing the optic nerve at the entrance of the optic canal. However, a previous image that was taken 17 years back revealed that the OA was normal, which suggested the change in dolichoectasia was acquired. Cerebral angiography showed that the dilated and tortuous OA was running from the ophthalmic segment of the left internal carotid artery into the orbit. The symptoms could have been attributed to the direct compression of the dolichoectatic OA in the optic canal. A sufficient anastomosis between the central retinal artery and the middle meningeal artery was identified on external carotid angiography with balloon occlusion of the internal carotid artery. Endovascular treatment with internal trapping of the OA was performed due to ophthalmic symptom progression. Internal coil trapping of the OA was performed at the short segment between the OA bifurcation and the entrance of the optic canal. As expected, the central retinal artery was supplied via the middle meningeal artery after the treatment. The transient visual disturbance was immediately resolved. Ophthalmalgia worsened temporarily after the treatment. However, it completely resolved after several days of oral corticosteroid therapy. Postoperative angiography showed that the origin of the OA was occluded and that the OA in the optic canal was shrunk. The flow of the central retinal arteries via the middle meningeal artery was preserved., Conclusions: OA dolichoectasia is rare, and its pathogenesis and long-term visual prognosis are still unknown. However, endovascular therapy can improve symptom by releasing the pressure site in the optic canal., (© 2024. The Author(s).)

Background: Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry., Case Presentation: We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain., Conclusions: This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry., (© 2023. The Author(s).)

Purpose: The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which is exclusive to the Asian population, is related to many diseases. A high reactive oxygen species production in mitochondria, and low muscle strength in athletes and non-athletes, has been observed, as our previous study demonstrated. The purpose of this research was to investigate the influence of ALDH2 rs671 on the loss of muscle strength with aging and replicate our previous study in non-athletes., Methods: Healthy Japanese individuals (n = 1804) aged 23-94 years were genotyped using DNA extracted from saliva. Muscle strength was assessed using grip strength and chair stand test (CST). The interaction between age and genotypes was analyzed by two-way analysis of covariance (ANCOVA) adjusted for sex, body mass index (BMI), and exercise habit., Results: Individuals aged ≧55 with the AA genotype had a lower performance than those with the GG + GA genotype in the grip strength test (28.1 ± 9.1 kg vs. 29.1 ± 8.3 kg, p = 0.021). There was an interaction between age and genotype, where individuals with ≧55 years old AA genotype had a higher loss of strength compared to GG + GA genotypes in the CST (0.025). No interaction in other models and no sex differences were found., Conclusion: This study replicated previous results of the relationship between the AA genotype with lower muscle strength and as a novelty showed that this genotype is associated with a higher age-related loss of strength., (© 2022. The Author(s).)

Purpose: A distal femoral trial component was manufactured, and flexion gap size and inclination were evaluated with or without the distal femoral trial component in total knee arthroplasty (TKA). This study aimed to evaluate the effect of the distal femoral trial component on flexion gap size and joint inclination in posterior-stabilized (PS)-TKA., Materials and Methods: A total of 84 patients with medial osteoarthritis who underwent mobile-bearing PS-TKA using modified gap techniques were included in this retrospective study. The flexion gap size and inclination before and after setting the distal femoral trial component were evaluated and compared with the final gap size and inclination., Results: The joint gap size and inclination were significantly lower in those with than in those without the distal femoral trial component (P = 0.005, P < 0.001). The final gap size and inclination were similar to the gap size and inclination with the distal trial component (P = 0.468, P = 0.158)., Conclusions: The joint gap size and medial tension in PS-TKA were significantly reduced after setting the distal femoral trial component. The flexion gap measured using the distal femoral trial component was similar to that when the final trial component was set. To more accurately perform the gap technique TKA, the flexion gap should be measured using the distal femoral trial component., (© 2022. The Author(s).)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphatic tumor; however, extranodal DLBCLs that exhibit initial symptoms in the maxilla and mandible are rare. Moreover, DLBCL is clinically classified as a moderate to highly malignant lymphatic tumor that can progress rapidly; therefore, early diagnosis is crucial. However, diagnosis is difficult as the disease causes a diverse range of clinical symptoms with no characteristic imaging findings. We conducted a clinical investigation to clarify the clinical characteristics of DLBCL that exhibits initial manifestation in the maxilla and mandible., Methods: Of the 2748 patients with malignant tumors of the oral and maxillofacial region examined at our hospital during a period of 11 years between January 2006 and December 2016, 27 primary cases diagnosed with DLBCL based on the chief complaint of symptoms in the gingiva and bone of the maxilla and mandible were enrolled in this study. Evaluations were based on sex, age, whether treatment was provided by a previous physician, symptoms, duration of disease until treatment was sought, clinical diagnosis, laboratory findings, and imaging results., Results: There were 15 cases that involved the maxilla and 12 that involved the mandible. The median duration of disease until treatment was sought was 60 d (3-450 d). All cases exhibited a tumor or a mass, and hypoesthesia of the chin was confirmed in eight cases wherein the mandible was involved. The clinical stages were stage I in eight cases, stage II in ten cases, and stage IV in nine cases. Serum lactate dehydrogenase (LDH) levels were elevated in 13 of 22 patients. The overall survival rate was 63%., Conclusions: Symptoms associated with nontender swelling and numbness of the lip or chin in the absence of other findings such as dental infections should raise suspicions about DLBCL. Patients should be provided appropriate imaging and accurate biopsy assessments to improve prognosis., (© 2022. The Author(s).)

Background: Metastasis of infradiaphragmatic tumors to the left supraclavicular lymph node is reported to be rare. When metastasis is detected in the left supraclavicular node in patients with head and neck carcinoma, locating the primary cancer remains a difficult and time-consuming challenge despite the dramatic development of screening technologies and treatment methods., Case Presentation: We report three cases of malignant infradiaphragmatic tumor diagnosed following an initial finding of left supraclavicular node metastasis after surgery for tongue squamous cell carcinoma (follow-up period, range 18-62 months). In these cases, adenocarcinoma was diagnosed based on left supraclavicular node biopsies, and a second primary tumor was found, in a 78-year-old Japanese woman with a diagnosis of cholangiocarcinoma, a 64-year-old Japanese man with a diagnosis of bladder carcinoma, and a 61-year-old Japanese man with a diagnosis of prostate carcinoma. In the cholangiocarcinoma case, carbohydrate antigen 19-9 and alpha-fetoprotein levels helped to diagnose cholangiocarcinoma. Palliative care only was given, with survival for 11 months after diagnosis of lymph node metastasis. In the bladder carcinoma case, pathological analysis of fine-needle aspiration biopsy specimen of the metastatic cervical lymph node showed atypical cells with slight squamous differentiation. Hematoxylin-eosin staining of the bladder lesion did not identify a clear glandular or squamous component, and we could not make a definitive diagnosis of whether the lesion was poorly differentiated squamous cell carcinoma, adenocarcinoma, or high-grade urothelial carcinoma. GATA3 staining aided in the diagnosis of urothelial bladder cancer with left supraclavicular node metastasis. He survived for 2 months after diagnosis of left supraclavicular lymph node metastasis. In the prostate carcinoma case, 18 F-fluorodeoxyglucose uptake was weak. Prostate-specific antigen levels and magnetic resonance imaging findings aided the diagnostic process. This patient underwent bilateral orchiectomy and adjuvant hormonal therapy and survived for 47 months after diagnosis of left supraclavicular node metastasis., Conclusions: Pathological diagnosis on the basis of immunohistochemistry and specific diagnosis methods such as radiological and serological assessments are important for providing rapid diagnosis and appropriate treatment., (© 2022. The Author(s).)

Background: The detailed neuropathological features of patients with autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (TCC) and SPG11 mutations are poorly understood, as only a few autopsies have been reported. Herein, we describe the clinicopathological findings of a patient with this disease who received long-term care at our medical facility., Case Presentation: A Japanese man exhibited a mild developmental delay in early childhood and intellectual disability, followed by the appearance of a spastic gait by age 13. At the age of 25 years, he became bedridden and needed a ventilator. Genetic analysis revealed a homozygous splice site variant in the SPG11 gene (c. 4162-2A > G) after the provision of genetic counselling and acquisition of informed consent from his parents. He died of pneumonia at the age of 44. His brain weighed 967 g and was characterized by a TCC, and his spinal cord was flattened. Microscopically, degeneration was observed in the posterior spinocerebellar tract, the gracile fasciculus, and the posterior column in addition to the corticospinal tract. Marked neuronal loss and gliosis were observed in the anterior horn, Clarke's column, and hypoglossal and facial nuclei. Various types of neurons, in addition to motor neurons, showed coarse eosinophilic granules that were immunoreactive for p62. The loss of pigmented neurons with gliosis was apparent in both the substantia nigra and locus coeruleus. Lateral geniculate body degeneration was a characteristic feature of this patient. Furthermore, peripheral Lewy body-related α-synucleinopathy and scattered α-synuclein-immunoreactive neurites in the locus coeruleus and reticular formation of the brainstem were observed., Conclusions: In patients with hereditary spastic paraplegia with SPG11 mutations, a variety of clinical phenotypes develop due to widespread lesions containing p62-immunoreactive neuronal cytoplasmic inclusions. We herein report the lateral geniculate body as another degenerative site related to SPG11-related pathologies that should be studied in future investigations., (© 2021. The Author(s).)

Background: Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed., Methods: This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety., Discussion: This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples., Trial Registration: The Japan Registry of Clinical Trials  jRCTs071200031 .  Registered on 7 December 2020., (© 2021. The Author(s).)

Background: Left ventricular (LV) involvement in diabetic cardiomyopathy has been reported; however, only limited data exist on right ventricular (RV) involvement. Therefore, our purpose was to investigate RV systolic dysfunction and its association with LV longitudinal myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) and preserved LV ejection fraction (LVEF)., Methods: We studied 177 T2DM patients with preserved LVEF and 79 age-, sex-, and LVEF-matched healthy volunteers. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), and RV systolic function was assessed as RV free-wall strain, and predefined cutoff values for subclinical dysfunction were set at GLS < 18% and RV free-wall strain < 20%, respectively., Results: RV free-wall strain in T2DM patients was significantly lower than that in normal controls (19.3% ± 4.8% vs. 24.4% ± 5.1%; P < 0.0001). RV free-wall strain in T2DM patients and LV longitudinal dysfunction was similar compared to that in T2DM patients without (19.0 ± 4.5% vs. 19.6 ± 5.0%, P = 0.40). Furthermore, multivariate logistic regression analyses showed that GLS was independently associated with RV systolic dysfunction as well as mitral inflow E and mitral e' annular velocities ratio (odds ratio, 1.16; 95% confidence interval: 1.03-1.31; P < 0.05). Sequential logistic models evaluating the association of RV systolic dysfunction in T2DM patients showed an improvement in clinical variables (χ 2  = 6.2) with the addition of conventional echocardiographic parameters (χ 2  = 13.4, P < 0.001) and a further improvement with the addition of GLS (χ 2  = 20.8, P < 0.001)., Conclusion: RV subclinical systolic dysfunction was observed in T2DM patients with preserved LVEF and was associated with LV longitudinal myocardial dysfunction. Our findings may provide additional findings for the management of T2DM patients., (© 2021. The Author(s).)

Background: Oral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear., Methods: We designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded., Results: The study population included 123 men and 442 women aged 21-93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type., Conclusions: Our results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.

Background: Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain., Methods: We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS < 18%., Results: GLS in T2DM patients with high HR was significantly lower than that in T2DM patients with low HR (16.3% ± 4.2% vs. 17.8% ± 2.8%; P = 0.03), whereas GLS in normal subjects with high and low HR was similar (20.3 ± 1.7% vs. 20.3 ± 2.0%; P = 0.99). Multivariable logistic regression analysis showed that high HR (odds ratio: 1.04; 95% confidence interval: 1.01-1.07; P = 0.01) was independently associated with GLS < 18% in T2DM patients as well as HbA1c, T2DM duration, LVEF, body mass index, and mitral inflow E and mitral e' annular velocity ratio. One sequential logistic model evaluating the associations between GLS < 18% and clinical variables in T2DM patients showed an improvement with the addition of LVEF and E/e' (P < 0.001) and a further improvement with the addition of high HR (P < 0.001)., Conclusion: Compared with normal subjects, resting HR was associated with LV longitudinal myocardial function in asymptomatic T2DM patients with preserved LVEF. Our findings provide new insights on the management of T2DM patients.

Background: In total knee arthroplasty (TKA) using the modified gap technique, the soft-tissue balance is measured after osteotomy of the distal femur and proximal tibia (conventional bone gap). However, after osteotomy, the flexion gap size during 90° knee flexion may be larger than that observed after implantation. The tension of the lateral compartment during 90° flexion may also be reduced after osteotomy of the distal femur. We manufactured a distal femoral trial component to reproduce the condition after implantation and prior to posterior condyle osteotomy. This study aimed to evaluate the effect of the trial component on the flexion gap., Methods: This prospective study included 21 consecutive patients aged 78 years with medial osteoarthritis who underwent cruciate-retaining TKA between February 2017 and March 2018. The postoperative flexion gap size and inclination during 90° flexion were compared between cases with and without the trial component., Results: The mean joint gap size with the trial component (13.4 ± 0.80 mm) was significantly smaller than that without the trial component (14.7 ± 0.84 mm). The mean gap inclination angle with the trial component (3.7° ± 0.62°) was significantly smaller than that without the trial component (5.5° ± 0.78°)., Conclusions: In the present study, the joint gap size and medial tension were significantly reduced after the trial component had been set. Accurate measurement of the soft-tissue balance is an important factor in the modified gap technique, and this method using a distal femoral trial component can offer better outcomes than those achieved with conventional methods., (© 2021. The Author(s).)

Background: The concept of minimally invasive surgery (MIS) was introduced in total knee arthroplasty (TKA) in the late 1990s. The number of MIS TKAs has clearly decreased in recent years. An implant designed specifically for MIS TKA has been used all over the world, but there are no reports of long-term postoperative results. The purpose of this study was to characterize long-term clinical results with a minimum follow-up of 10 years., Methods: This retrospective study included 109 consecutive patients with 143 NexGen CR-Flex prostheses, which are MIS tibial component prostheses designed specifically for MIS TKA. Twelve-year survival analysis was performed using Kaplan-Meier method. Revision surgery for any reason was the endpoint. Long-term clinical and radiographic results of 74 knees (55%) in 60 patients with more than 10 years of follow-up were analyzed., Results: The cumulative survival rate of the single-radius posterior-stabilized TKA of 74 knees was 94.7% (95% confidence interval, 90-99%) at 12 years after surgery. Seven knees (9%) required additional surgery during the 10-year follow-up because of periprosthetic infections. Mean postoperative Knee Society knee score and functional score were 91 and 74 points, respectively. There were no cases of prosthesis breakage, polyethylene wear, or aseptic loosening of the prosthesis., Conclusion: The prosthesis designed specifically for MIS TKA is associated with good survival and clinical results with a minimum follow-up of 10 years, even though MIS TKA has become less popular., Level of Evidence: III.

Background: Renal hypouricemia (RHUC) is a genetic disorder caused by mutations in the SLC22A12 gene, which encodes the major uric acid (UA) transporter, URAT1. The clinical course of related, living donor-derived RHUC in patients undergoing kidney transplantation is poorly understood. Here, we report a case of kidney transplantation from a living relative who had an SLC22A12 mutation. After the transplantation, the recipient's fractional excretion of UA (FEUA) decreased, and chimeric tubular epithelium was observed., Case Presentation: A 40-year-old man underwent kidney transplantation. His sister was the kidney donor. Three weeks after the transplantation, he had low serum-UA, 148.7 μmol/L, and elevated FEUA, 20.8% (normal: < 10%). The patient's sister had low serum-UA (101.1 μmol/L) and high FEUA (15.8%) before transplant. Suspecting RHUC, we performed next-generation sequencing on a gene panel containing RHUC-associated genes. A heterozygous missense mutation in the SLC22A12 gene was detected in the donor, but not in the recipient. The recipient's serum-UA level increased from 148.7 μmol/L to 231.9 μmol/L 3 months after transplantation and was 226.0 μmol/L 1 year after transplantation. His FEUA decreased from 20.8 to 11.7% 3 months after transplantation and was 12.4% 1 year after transplantation. Fluorescence in situ hybridization of allograft biopsies performed 3 months and 1 year after transplantation showed the presence of Y chromosomes in the tubular epithelial cells, suggesting the recipient's elevated serum-UA levels were owing to a chimeric tubular epithelium., Conclusions: We reported on a kidney transplant recipient that developed RHUC owing to his donor possessing a heterozygous mutation in the SLC22A12 (URAT1) gene. Despite this mutation, the clinical course was not problematic. Thus, the presence of donor-recipient chimerism in the tubular epithelium might positively affect the clinical course, at least in the short-term.

Background: The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear., Methods: We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views., Results: E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p < 0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HF with preserved ejection fraction patients was more significant from 17.0 ± 1.9% to 18.7 ± 2.0% (p < 0.001), compared to that in HF with mid-range ejection fraction and HF with reduced ejection fraction patients from 14.4 ± 2.4% to 15.5 ± 1.8% (p = 0.06) and from 8.1 ± 1.5% to 7.8 ± 2.1% (p = 0.44), respectively. It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameters for the change in E/e' after administration of dapagliflozin., Conclusion: Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF.

Background: Type 2 diabetes mellitus (T2DM) is a major cause of heart failure (HF) with preserved ejection fraction (HFpEF), usually presenting as left ventricular (LV) diastolic dysfunction. Thus, LV diastolic function should be considered a crucial marker of a preclinical form of DM-related cardiac dysfunction. However, the impact of glycemic variability (GV) on LV diastolic function in such patients remains unclear., Methods: We studied 100 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease (age: 60 ± 14 years, female: 45%). GV was evaluated as standard deviation of blood glucose level using continuous glucose monitoring system for at least 72 consecutive hours. LV diastolic function was defined as mitral inflow E and mitral e' annular velocities (E/e'), and > 14 was determined as abnormal., Results: E/e' in patients with high GV (≥ 35.9 mg/dL) was significantly higher than that in patients with low GV (11.3 ± 3.9 vs. 9.8 ± 2.8, p = 0.03) despite similar age, gender-distribution, and hemoglobin A1c (HbA1c). Multivariate logistic regression analysis showed that GV ≥ 35.9 mg/dL (odds ratio: 3.67; 95% confidence interval: 1.02-13.22; p < 0.05) was an independently associated factor, as was age, of E/e' > 14. In sequential logistic models for the associations of LV diastolic dysfunction, one model based on clinical variables including age, gender and hypertension was not improved by addition of HbA1c (p = 0.67) but was improved by addition of high GV (p = 0.04)., Conclusion: Since HFpEF is a syndrome caused by diverse agents, reducing GV may represent a potential new therapeutic strategy for the prevention of the development of HFpEF in T2DM patients.

Background: Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method., Methods: This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them., Results: Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm. Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes., Conclusions: We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

Background: Inconsistency of treatment response in cats with obstructive hypertrophic cardiomyopathy is well recognized. We hypothesized that the difference in response to beta-blockers may be caused by myocardial functional abnormalities. This study was designed to compare myocardial function in cats with obstructive hypertrophic cardiomyopathy with and without response to beta-blockers. Twenty-one, client-owned, hypertrophic cardiomyopathy cats treated with carvedilol were analyzed. After carvedilol treatment, cats with decreased left ventricular outflow tract velocity were categorized as responders (n = 10); those exhibiting no response (no decrease in the left ventricular outflow tract velocity) were categorized as non-responders (n = 11). The cats were examined using layer-specific assessment of the myocardial function (whole, endocardial, and epicardial layers) longitudinally and circumferentially by two-dimensional speckle-tracking echocardiography, before and after carvedilol treatment., Results: The non-responder cats had a significantly higher age, end-diastolic left ventricular posterior-wall thickness, peak velocity of left ventricular outflow tract, and dose of carvedilol than the responders (p = 0.04, p < 0.01, p < 0.01, and p < 0.01, respectively). The circumferential strain in the epicardial layer was lower and circumferential endocardial to epicardial strain ratio was higher in non-responders than responders (p < 0.001 and p = 0.006). According to the multivariate analysis, circumferential strain in the epicardial layer was the only independent correlate of treatment response with carvedilol., Conclusions: Myocardial function, assessed by two-dimensional speckle-tracking echocardiography, differed in cats with hypertrophic cardiomyopathy with and without response to beta-blockers. The determination of layer-specific myocardial function may facilitate detailed pathophysiologic assessment and treatment response in cats with hypertrophic cardiomyopathy.

Background: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied., Methods: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining., Results: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy., Conclusions: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.

Background: High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient's prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage., Methods: This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis., Results: Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43-4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50-10.4; P = 0.005) had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07-2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23-1.59; P < 0.001)., Conclusions: Although the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient's calcium level.

Background: Malignancies occur in approximately 1:1000 pregnancies; the most common being breast (46%) and hematological (18%) malignancies. Oral cancers account for only 2% of all cancers in pregnant women, and there are no standard guidelines for the treatment of oral cancer during pregnancy., Methods: Between 2007 and 2014, our department managed 1109 patients with oral cancers; four (0.4%) had tongue carcinomas during pregnancy. These cases were retrospectively reviewed., Results: The four women were aged 29-39 (median 32.5) years. Two underwent partial glossectomy at 39 and 40 weeks' gestation, respectively, one received radiotherapy at 17 weeks' gestation, and one underwent supraomohyoid neck dissection and hemi-glossectomy with a forearm flap reconstruction., Conclusion: In addition to tumor factors, the wishes of the patient and her family, gestational age, and fetal and maternal conditions are important factors in deciding on a treatment protocol. Moreover, treatment decisions require multidisciplinary approach.

Background: Many reports argue that sleep is important for children's health, learning, and academic performance. The purpose of this longitudinal study was to examine the association between sleep and the development of social competence in infants., Methods: This study was conducted as part of a Japan Science and Technology Agency (JST) project. Caregivers responded to the Japan Children's Study Sleep Questionnaire when children were 18 months old. The interactions of caregivers and children were observed when children were 18, 30, and 42 months old, and rated with the Interaction Rating Scale, which is a measure of social competence., Results: Nocturnal sleep duration of more than 10 h and an earlier bed time than 22:00 were significantly correlated with two trajectory groups (low point and high point transition groups) of children's social competence at 18, 30, and 42 months. Further, total sleep duration of more than 12.25 h and an earlier bed time than 22:00 were significantly correlated with the trajectory of children's social competence at 18, 30, and 42 months., Conclusions: Sleep duration and sleep onset time are important factors in children's development of social competence. Trial registration The ethics committee of the JST approved this study on March 19, 2001. The registration number is 356-1.

Background: Perioperativemanagement of hemodialysis patients involves many difficulties. High mortality rate and circulatory or respiratory complications in these patients were reported. However, in such reports, there is no concrete information of perioperative management in hemodialysis patients to prevent surgical complications and successful outcomes., Case Presentation: We retrospectively reviewed the cases of 5 hemodialysis patients who underwent oral surgery under general anesthesia between January 2005 and December 2017. Primary disease was oral squamous cell carcinoma (SCC) in 4 patients and mandibular ameloblastoma in 1 patient. Partial resection was performed in 2 cases, neck dissection in 1 case. Two cases underwent surgery including vascularized reconstruction. The patients were dialyzed the day before and after surgery for the control of fluid and electrolyte status. Patients received intraoperative and postoperative intravenous infusion of potassium-free solution at 20-40 mL/h. Erythropoiesis-stimulating agents (ESAs) were used on the day of hemodialysis during hospitalization. Nafamostat mesilate as an anticoagulant during hemodialysis were used from postoperative day (POD)1 to 7. From POD 1 to 10, cephalosporin as prophylactic antibiotics is adjusted to quarter from half the initial dose. The resuming time of oral intake was similar to that of other oral surgery patients without kidney disease. The daily intake limits of protein, salt and liquid were managed during hospitalization and no cases suffered from malnutrition. No cardiorespiratory complications occurred during the perioperative period. In a case of vascularized osteocutaneous scapular flap reconstruction, grafted scapular bone survived and scapular cutaneous flap necrotized. Necrotic tissue was debrided and split thickness skin was successfully used to cover the grafted scapular bone., Conclusions: Postoperative better result could be achieved if adequate perioperative management specific to hemodialysis patients is carried out. Vascularized flap reconstruction at oral and maxillofacial region in hemodialysis patients is beneficial treatment. Even if the first flap has wound complication secondary flap reconstruction is success and aesthetically better results could be achieved by the strict wound management and debridement.

Background: The objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF)., Methods: This trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. The physical examinations, blood tests, and echocardiography were performed at baseline and 6 months after administration of dapagliflozin. The primary endpoint was defined as a change in mitral inflow E and mitral e' annular velocities (E/e') between baseline and 6 months after the administration of dapagliflozin. The secondary end points consisted of a change in brain natriuretic peptide (BNP), LV mass index (LVMI) and left atrial volume index (LAVI)., Results: E/e' significantly decreased from 9.3 to 8.5 cm/s (p = 0.020) 6 months after administration of dapagliflozin. LAVI and LVMI significantly decreased from 31 to 26 mL/m 2 (p = 0.001), and from 75.0 to 67.0 g/m 2 (p < 0.001), respectively, 6 months after administration of dapagliflozin. No significant change was observed in BNP (from 27.9 to 28.9 pg/mL; p = 0.132) 6 months after administration of dapagliflozin, except for a significant decrease from 168.8 to 114.3 pg/mL (p = 0.012) in patients with BNP ≥ 100 pg/mL., Conclusion: This prospective multicenter trial showed the beneficial effect of SGLT2 inhibitors on LV diastolic functional parameters for T2DM patients with HF. Our findings may thus offer a new insight into the management of T2DM patients. Trial registration UMIN000019789, Registered 28 September 2014, Date of registration: 11/14/2015, Date of enrolment of the first participant to the trial: 6/15/2016, Date of enrolment of the last participant to the trial: 12/9/2017.

Background: Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. Although the mechanisms of DM-related LV myocardial injury are complex, it has been postulated that overweight contributes to the development of LV myocardial injury in type 2 diabetes mellitus (T2DM) patients. However, the precise impact of overweight on LV longitudinal myocardial systolic function in T2DM patients remains unclear., Methods: We studied 145 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease. LV longitudinal myocardial systolic function was assessed by global longitudinal strain (GLS), which was defined as the average peak strain of 18-segments obtained from standard apical views. Overweight was defined as body mass index (BMI) ≥ 25 kg/m 2 . Ninety age-, gender- and LVEF-matched healthy volunteers served as controls., Results: GLS of overweight T2DM patients was significantly lower than that of non-overweight patients (17.9 ± 2.4% vs. 18.9 ± 2.6%, p < 0.05), whereas GLS of both overweight and non-overweight controls was similar (19.8 ± 1.3% vs. 20.4 ± 2.1%, p = 0.38). Furthermore, multiple regression analysis revealed that for T2DM patients, BMI was the independent determinant parameters for GLS as well as LV mass index., Conclusions: Overweight has a greater effect on LV longitudinal myocardial systolic function in T2DM patients than on that in non-DM healthy subjects. Our finding further suggests that the strict control of overweight in T2DM patients may be associated with prevention of the development of HFpEF.

In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.

Background: Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully., Case Presentation: We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic., Conclusions: To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.

Background: Subclinical left ventricular (LV) longitudinal myocardial systolic dysfunction occurs in patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF), and is closely related to DM-related complications. However, the association of diabetic neuropathy (DN) with subclinical LV systolic longitudinal dysfunction in such patients has not been fully clarified., Methods: The subjects of this study were 112 consecutive DM patients with preserved LVEF (all ≥50%) without coronary artery disease and overt heart failure (aged 59 ± 14 years; 60 women, 52 men). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. DN was diagnosed by experienced diabetologists. Median, ulnar, and sural nerves were subjected to motor and sensory nerve conduction studies. F-wave latency was defined as the minimum F-wave latency after a total of 16 stimulations of the tibial nerve., Results: Forty-one (37%) patients were clinically diagnosed with DN. LV functions of DM patients with and without DN were similar except for GLS being significantly smaller in patients with than in patients without DN (18 ± 2% vs. 20 ± 2%, p < 0.001). It was noteworthy that, of the parameters for the nerve conduction study, only F-wave latency correlated with GLS (r = -0.34, p < 0.001), and also was identified as an independent determinative value of GLS in a multivariate linear regression model (β = -0.25, p = 0.001) even after adjustment for other closely related GLS factors., Conclusions: Monitoring of F-wave latency may aid early detection of not only DN but also subclinical LV dysfunction. Joint planning of assessment by diabetologists and cardiologists is therefore advisable for better management of DM patients.

Background: Left ventricular (LV) longitudinal systolic dysfunction has been identified even in asymptomatic patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF). However, its relevant clinical features have not been fully evaluated., Methods: We studied 144 asymptomatic DM patients without coronary artery disease. Their mean age was 57 ± 15 years, 79 (55%) were female, and mean LVEF was 66 ± 4% (all ≥50%). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. With the pre-defined cutoff for subclinical LV systolic dysfunction in DM patients with preserved LVEF set at GLS < 18%, this dysfunction was detected in 53 patients (37%)., Results: Multivariate logistic regression analysis revealed that type 2 DM, hypertriglyceridemia, overweight/obesity, nephropathy and neuropathy were independently associated with GLS < 18%, with nephropathy being the highest risk factor (OR: 5.26; 95% CI 2.111-13.12, p < 0.001). For sequential logistic regression models, a model based on clinical variables including gender, type 2 DM and DM duration (χ(2) = 24.1) was improved by addition of overweight/obesity and hypertriglyceridemia (χ(2) = 45.6, p < 0.001), and further improved by addition of nephropathy and neuropathy (χ(2) = 70.2, p < 0.001) as variables. Furthermore, albuminuria significantly correlated with GLS (r = -0.51, p < 0.001), and a multivariate regression model showed it to be the factor most closely associated with GLS (β = -0.33, p < 0.001)., Conclusions: Diabetic complications, hypertriglyceridemia and overweight/obesity were closely associated with early stage of LV systolic longitudinal myocardial dysfunction in asymptomatic DM patients with preserved LVEF. Our findings can be clinically noticeable for the management of DM patients.

Background: Cardiac metastasis of renal cell carcinoma is an exceptional event, particularly when there is lack of inferior vena cava involvement. Indeed, only a few cases have been reported worldwide thus far. Moreover, discussion of treatment and follow-up strategies for cardiac metastasis of renal cell carcinoma is important because of the high risk of sudden death., Case Presentation: We report the case of a 75-year-old Japanese man with metastatic tumor in the left atrium from renal cell carcinoma. He had a history of right renal cell carcinoma, for which he had undergone hand-assisted laparoscopic nephrectomy. Lung and bone metastases were detected after nephrectomy, and treatment with interferon-alpha was initiated. After disease progression, he was treated concurrently with targeted molecular therapy and radiotherapy for bone metastasis. After these therapies, a 42 × 24 mm mass was found on transthoracic echocardiography in left atrium without involvement of the right atrium or inferior vena cava. The provisional diagnosis was metastatic mass or myxoma, and surgical resection was performed. Histopathological examination led to a final diagnosis of metastatic tumor from clear cell renal cell carcinoma., Conclusion: Cardiac metastasis, metastasis to the left atrium in particular, is rare in patients with renal cell carcinoma. In our study, surgery of the cardiac mass was effective to avoid sudden death and quality of life decline resulting from heart failure. We describe this case and review cardiac metastasis of renal cell carcinoma.

Background: The library size is critical for selection in evolutionary molecular engineering (directed evolution). Although cDNA display has become a promising in vitro display technology by overcoming the instability of mRNA display, it is hindered by low yields. In this study, we improved the yield of cDNA display molecules by carefully examining each step of the preparation process., Findings: We found that steric hindrance of ribosomes binding to the mRNA-protein fusion molecules was interfering with biotin-streptavidin binding. Additionally, reducing buffer exchange by performing RNase digestion in the His-tag-binding buffer to release the cDNA display molecules improved their His-tag purification., Conclusion: Our optimized conditions have improved the yield of cDNA display molecules by more than 10 times over currently used methods, making cDNA display more practically available in evolutionary molecular engineering.

Background: Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types., Methods: Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients., Results: Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days)., Conclusions: Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy.

Introduction: Küttner's tumor is characterized through histology by peri-ductal fibrosis, dense lymphocytic infiltration with lymphoid follicles, loss of acini, and occasional marked sclerosis of the salivary gland. On occasion, Küttner's tumor can be difficult to distinguish from malignant neoplasm., Case Presentation: A 58-year-old Japanese man was referred to our hospital with a three-month history of a painless swollen mass in the right sub-mandibular region. Histological findings revealed both lymphoid follicles with reactive germinal centers and variously sized lymphoid follicle-like nodules without definitive germinal centers or mantle zones. B-cells of similar size and shape occupied the lymphoid follicle-like nodules and stained positive for B-cell lymphoma. These cells were detected in the polyclonal B-cells by flow cytometric analysis and tested negative for CD10. Unusual B-cell proliferation was observed, but as there was no definitive evidence of B-cell lymphoma, the lesion was diagnosed as Küttner's tumor., Conclusion: We report on a rare case of Küttner's tumor associated with fibrosclerosis and atypical lymphoid hyperplasia in both the sub-mandibular gland and regional lymph nodes. Although more cases need to be investigated, our findings might be helpful to further studies seeking to clarify the etiology of idiopathic sclerosing lesions arising in the organs and regional lymph nodes.

Background: Selective serotonin-reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depression and can be used as nonhormonal alternatives to manage hot flashes for women with a history of breast cancer and unable to take hormone replacement therapy. There are, however, few reports on the efficacy of SSRIs for the treatment of natural postmenopausal climacteric symptoms. In this pilot study, we evaluate the SSRI, fluvoxamine, for controlling climacteric symptoms and vasomotor symptoms, in particular., Methods: Twenty-two patients were enrolled from our hospital. All were orally administered fluvoxamine (50 mg daily). Climacteric and depressive symptoms were assessed using simple menopausal index (SMI) and self-rating questionnaire for depression (SRQ-D), respectively, at baseline, and at 2 and 6 weeks post-treatment., Results: Six weeks following drug administration, neither the SRQ-D nor SMI scores significantly decreased compared to baseline. The mean levels of vasomotor symptoms and mental symptoms decreased significantly following fluvoxamine administration, while skeletal muscle symptom scores did not., Conclusion: We were able to demonstrate that fluvoxamine was effective in treating not only depressive moods in climacteric symptoms but also the associated vasomotor symptoms. There are several limitations to this preliminary study. Future controlled studies are needed to further evaluate the efficacy of fluvoxamine for climacteric disturbances.

Background: In order to understand microarray data reasonably in the context of other existing biological knowledge, it is necessary to conduct a thorough examination of the data utilizing every aspect of available omic knowledge libraries. So far, a number of bioinformatics tools have been developed. However, each of them is restricted to deal with one type of omic knowledge, e.g., pathways, interactions or gene ontology. Now that the varieties of omic knowledge are expanding, analysis tools need a way to deal with any type of omic knowledge. Hence, we have designed the Omic Space Markup Language (OSML) that can represent a wide range of omic knowledge, and also, we have developed a tool named GSCope3, which can statistically analyze microarray data in comparison with the OSML-formatted omic knowledge data., Results: In order to test the applicability of OSML to represent a variety of omic knowledge specifically useful for analysis of Arabidopsis thaliana microarray data, we have constructed a Biological Knowledge Library (BiKLi) by converting eight different types of omic knowledge into OSML-formatted datasets. We applied GSCope3 and BiKLi to previously reported A. thaliana microarray data, so as to extract any additional insights from the data. As a result, we have discovered a new insight that lignin formation resists drought stress and activates transcription of many water channel genes to oppose drought stress; and most of the 20S proteasome subunit genes show similar expression profiles under drought stress. In addition to this novel discovery, similar findings previously reported were also quickly confirmed using GSCope3 and BiKLi., Conclusion: GSCope3 can statistically analyze microarray data in the context of any OSML-represented omic knowledge. OSML is not restricted to a specific data type structure, but it can represent a wide range of omic knowledge. It allows us to convert new types of omic knowledge into datasets that can be used for microarray data analysis with GSCope3. In addition to BiKLi, by collecting various types of omic knowledge as OSML libraries, it becomes possible for us to conduct detailed thorough analysis from various biological viewpoints. GSCope3 and BiKLi are available for academic users at our web site http://omicspace.riken.jp.

Vascular endothelial growth factor (VEGF)-C, one of several members of the VEGF family, is a relatively specific lymphangiogenic growth factor. VEGF receptor (VEGFR)-3 (or Flt4) is a VEGF-C receptor with expression restricted to lymphatic endothelial cells. Since the mechanisms by which carcinoma cells metastasize to lymph nodes remain unclear, we constructed a VEGF-C transfectant (AZ-VEGF-C) from the AZ521 human gastric carcinoma cell line, which ordinarily shows little nodal metastatic potential and little VEGF-C expression. We orthotopically implanted transfected tumor cells into the stomachs of nude mice. The number of mice developing lymph node metastases and the number of lymph node metastases per mouse with nodal metastases were higher than with implants of mock-transfected control cells. Specifically, percentages of mice with lymph node metastases were 95.5% (21/22) for AZ-VEGF-C and 29.4% (5/17) for controls (P<0.01), while mean numbers of involved lymph nodes were 3.76 for AZ-VEGF-C and 1.00 for controls (P<0.01). No difference was found between AZ-VEGF-C and controls regarding cell growth and chemotactic responses in vitro, or in volumes of tumors arising from implanted cells. When we performed immunohistochemical staining for VEGFR-3 in these tumors to investigate lymphangiogenesis by VEGF-C, the number of vessels stained for VEGFR-3 in tumors and surrounding tissues was higher for AZ-VEGF-C than for controls. VEGFR-3-positive vessels occupied 14.9/1000 of microscopically examined areas for AZ-VEGF-C, but only 1.30/1000 for controls (P<0.001). Our results suggest that VEGF-C is a specific lymphangiogenic growth factor with an important role in lymph node metastasis.