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Background The association between delivery mode and subsequent development of diseases is a growing area of research. Cesarean delivery affects the diversity of the microbiota in the infant gut, which may be associated with gastrointestinal disorders, including functional constipation, in infants. In this study, we investigated the association between delivery mode and prevalence of functional constipation in 3-year-old Japanese toddlers. Methods This study used data from the Japan Environment and Children’s Study, an ongoing nationwide birth cohort study. We analyzed 71,878 toddler–mother pairs. The presence of functional constipation was determined according to the Rome III diagnostic criteria. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. Results The prevalence of functional constipation in 3-year-old Japanese toddlers was estimated to be 12.3%. Logistic regression analysis revealed that the prevalence of functional constipation was higher in toddlers born by cesarean delivery (13.1%) compared with those born by vaginal delivery (12.1%), independent of 22 confounders (adjusted odds ratios = 1.064, 95% confidence interval = 1.004–1.128). Conclusions We determined the prevalence of functional constipation in 3-year-old Japanese toddlers and found that delivery mode was associated with the prevalence of functional constipation in Japanese toddlers.

Identifying the cells from which cancers arise, and the paths they take towards malignancy, is critical for understanding the molecular basis of tumor initiation and progression. To understand if stem and progenitor cells can serve as cells of origin for cancer, we created a model in which the CreERT2 recombinase was knocked into the endogenous locus of the stem cell determinant Msi2. When crossed to a conditional CAG-LSL-MycT58A model, Msi2-CreERT2 mice developed a diversity of tumors across tissues, including multiple pancreatic cancer subtypes: pancreatic ductal adenocarcinoma (PDAC), adenosquamous carcinoma of the pancreas (ASCP), acinar cell carcinoma (ACC), and rare anaplastic tumors. Using single cell analysis, we traced the temporal changes that occurred as normal Msi2+ cells evolved through a pre-cancerous stage to PDAC, ASCP or ACC. These results revealed that Msi2+ cells were present predominantly in pancreatic ducts and exhibited heterogeneous differentiation states in the normal pancreas. At initiation, Myc triggered oncogenic transformation in the most undifferentiated subset leading to the rise of pre-cancer cells with multi-lineage properties. Subsequently, these pre-cancer cells were driven along different fates by epigenetically activated transcriptional programs with genomic changes amplifying the progression into distinct pancreatic cancer subtypes. Finally, integrating transcriptomic and functional genomic approaches in this new model allowed us to define Ifne, Ifitm3, Atf3, Hmmr, and Raet1e as novel functional dependencies of ASCP, giving us unique insight into the most lethal of pancreatic malignancies. These data show that multiple pancreatic cancer subtypes can arise from a common pool of pre-malignant cells and provide a powerful molecular framework to understand the programs that shape divergent fates in pancreas cancer and develop approaches for early detection and interception.

Patients with advanced heart failure often experience dyspnea, fatigue, edema, and appetite loss. If these symptoms are refractory to treatment, palliative care via a team approach is necessary. We describe a patient with stage D heart failure whose dyspnea and overall condition improved with comprehensive medical treatments including conventional medications for heart failure, continuous infusions of catecholamine and diuretic, and oral hydromorphone. A 67-year-old man with a 12-year history of dilated cardiomyopathy was admitted to our hospital due to exacerbation of heart failure. Despite continuous infusion of catecholamine and diuretic, his dyspnea and liver and renal function continued to worsen. Oral hydromorphone was administered to relieve his refractory dyspnea, which also improved his conditions, continuous infusion of the catecholamine and diuretic could withdraw. Oral low-dose hydromorphone used in the present case might be a helpful agent for treating dyspnea in stage D heart failure patients with renal dysfunction.

Introduction We previously reported that LP positive patients after percutaneous coronary intervention (PCI) had higher rate of re-hospitalization in the small-scale study (135 patients). In this study, we evaluated correlation between LP and later cardiac events leading to re-hospitalization more extensively in greater population. Methods and results A 24-h high-resolution (HR) ambulatory electrocardiogram (ECG) was performed in 421 patients that received PCI for the treatment of acute coronary syndrome (ACS) within 30 days. Various baseline characteristics and post-PCI ECG parameters including LP were examined for correlation with later re-hospitalization. LP was evaluated based on 3 different conditions, i.e., the worst, mean and best values, from 24-h signal-averaged QRS wave data. During the post-PCI follow-up period (611 ± 489.0 days), 90 patients were re-hospitalized due to cardiac events. Multivariate analysis identified only positive LP based on the worst value as an independent predictor for re-hospitalization with OR 2.26. Most of re-hospitalization cases (>75%) were predominantly attributed to ischemic events. LP positive population had significantly higher incidences of ischemic events as well as overall re-hospitalization compared to LP negative population. The predictive power of LP was decreased when it was combined with other variables. The receiver operating characteristic analysis determined the LP cut-off values consistent with the LP positive criteria previously reported and standardized. Conclusion The presence of LP in the 24-h HR ambulatory ECG post-PCI was an independent predictor for a risk of re-hospitalization due to ischemic cardiac events in ACS patients.

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Enteral nutrition is often performed in elderly patients with dysphagia. Choledocholithiasis is a disease that is common in elderly patients. Gastrointestinal hemorrhaging can occur in association with endoscopic sphincterotomy, and subsequent enteral nutrition must be carefully resumed. We herein report our experience using Mermed Plus containing sodium alginate after endoscopic hemostasis. The patient was an 88-year-old woman with an onset of gallstone cholangitis during rehabilitation after cerebral infarction. On day 2, endoscopic sphincterotomy and biliary drainage were performed, and the cholangitis was ameliorated. The degree of arousal and swallowing function were unstable, and a liquid diet via the nasogastric tube was initiated from day 6. Anemia progressed on day 7, and melena was observed; as a result, the intravenous administration of a proton pump inhibitor was initiated. On day 8, endoscopic hemostasis of the ulcer proximal to the papilla was performed. From day 10, we focused on the mucosal protective effects of sodium alginate, and Mermed Plus was initiated. No recurrence of hemorrhaging was observed. On day 13, the endoscopic findings revealed that the vicinity of the papilla was covered with solidified liquid diet, and the ulcer had healed. The postoperative course was uneventful, and swallowing training and rehabilitation were performed. On day 26, oral ingestion became possible. Many patients seem to be at risk of developing a gastrointestinal mucosal disorder when receiving enteral nutrition. In such cases, a liquid diet containing sodium alginate as dietary fiber is easy to use and may be useful for resuming enteral nutrition without delay.

Background Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrate high rates of co-infection with respiratory viruses, including influenza A (IAV), suggesting pathogenic interactions. Methods We investigated how IAV may increase the risk of COVID-19 lung disease, focusing on the receptor angiotensin-converting enzyme (ACE)2 and the protease TMPRSS2, which cooperate in the intracellular uptake of SARS-CoV-2. Results We found, using single-cell RNA sequencing of distal human nondiseased lung homogenates, that at baseline, ACE2 is minimally expressed in basal, goblet, ciliated and secretory epithelial cells populating small airways. We focused on human small airway epithelial cells (SAECs), central to the pathogenesis of lung injury following viral infections. Primary SAECs from nondiseased donor lungs apically infected (at the air-liquid interface) with IAV (up to 3×105 pfu; ~1 multiplicity of infection) markedly (eight-fold) boosted the expression of ACE2, paralleling that of STAT1, a transcription factor activated by viruses. IAV increased the apparent electrophoretic mobility of intracellular ACE2 and generated an ACE2 fragment (90 kDa) in apical secretions, suggesting cleavage of this receptor. In addition, IAV increased the expression of two proteases known to cleave ACE2, sheddase ADAM17 (TACE) and TMPRSS2 and increased the TMPRSS2 zymogen and its mature fragments, implicating proteolytic autoactivation. Conclusion These results indicate that IAV amplifies the expression of molecules necessary for SARS-CoV-2 infection of the distal lung. Furthermore, post-translational changes in ACE2 by IAV may increase vulnerability to lung injury such as acute respiratory distress syndrome during viral co-infections. These findings support efforts in the prevention and treatment of influenza infections during the COVID-19 pandemic., Shareable abstract (@ERSpublications) Influenza virus infection of cells lining the small airways increases the expression of molecules required for SARS-CoV-2 uptake in a manner that predicts increased severity of lung disease in those co-infected with influenza and coronaviruses https://bit.ly/3nu1WAo

The efficacy of rituximab for kidney disease, such as frequent relapsing nephrotic syndrome, has been reported recently. Herein, we report a case of a patient with acute kidney injury that was steroid-resistant nephrotic syndrome who responded to a single administration of low-dose rituximab. An 86-year-old Japanese woman with hypertension presented with severe peripheral edema within several days after onset. Due to the patient’s age, renal biopsy was not performed, nephrotic syndrome was diagnosed and prednisolone was administered at 40 mg/day on the day after admission. However, anuria developed and hemodialysis was inevitably initiated on the 5th hospital day. The renal function did not recover, and the general condition gradually became aggravated. On the 50th hospital day, 100 mg rituximab was administered, which led to immediate depletion of CD20-positive cells. The urine volume gradually increased from 2–3 weeks after the rituximab administration, and the renal function recovered slightly. After 5 weeks, it became possible to wean the patient from dialysis, which had been applied for 3 months. Rituximab might be an option for the treatment of acute kidney injury due to steroid-resistant nephrotic syndrome.

Transient late-onset hyperglycemia was detected in a very low birth weight (VLBW) infant (gestational age 28 weeks, birth weight 1,082 g) by routine point-of-care glucose monitoring. The infant had no clinical symptom. Serial continuous glucose monitoring (CGM) was conducted for 3 days at 31, 35, and 39 weeks' post conceptual age. The difference values between the maximum and minimum blood glucose levels during the interval from one enteral feeding to the next enteral feeding were 32.3±14.3 mg/dL, 47.5±22.9 mg/dL, and 27.5±12.9 mg/dL for the 1(st), 2(nd), and 3(rd) CGM, respectively. The serial change in the values was statistically significant (p

Proteinuria is a central component of chronic kidney disease and an independent risk factor for cardiovascular disease. Kidney podocytes have an essential role as a filtration barrier against proteinuria. Kruppel-like Factor 4 (KLF4) is expressed in podocytes and decreased in glomerular diseases leading to methylation of the nephrin promoter, decreased nephrin expression and proteinuria. Treatment with an angiotensin receptor blocker (ARB) reduced methylation of the nephrin promoter in murine glomeruli of an adriamycin nephropathy model with recovery of KLF4 expression and a decrease in albuminuria. In podocyte-specific KLF4 knockout mice, the effect of ARB on albuminuria and the nephrin promoter methylation was attenuated. In cultured human podocytes, angiotensin II reduced KLF4 expression and caused methylation of the nephrin promoter with decreased nephrin expression. In patients, nephrin promoter methylation was increased in proteinuric kidney diseases with decreased KLF4 and nephrin expression. KLF4 expression in ARB-treated patients was higher in patients with than without ARB treatment. Thus, angiotensin II can modulate epigenetic regulation in podocytes and ARB inhibits these actions in part via KLF4 in proteinuric kidney diseases. This study provides a new concept that renin-angiotensin system blockade can exert therapeutic effects through epigenetic modulation of the kidney gene expression.

A newborn male with pulmonary edema was delivered at term by elective Caesarian section. Cytokine profiles of 17 cytokines and KL-6 in cord blood and serial serum values were investigated. The cord blood values of all 17 cytokines and KL-6 were within normal limits. Subsequently, IL-6, IL-8, IL-10, IL-13, IL-17, and IFNγ rapidly elevated during the first several hours after birth and dramatically decreased thereafter, whereas KL-6 rose to 611 U/ml on the 3(rd) day of life and then gradually decreased. These cytokines may induce pulmonary permeability, and KL-6 secreted in lining fluid could result in influx into the bloodstream. This is the first report that we have differentiated neonatal pulmonary edema from TTN by the measurement of serial cytokine profiles and KL-6 in serum.

Background High-risk patients with Brugada syndrome (BrS) have inherent late potential (LP) fluctuations that might be explained by autonomic activity, electrolyte abnormality, and body temperature changes. However, the correlation between postural changes and LP determinates remains unknown. Methods Forty patients with BrS (38 men, 43.9 ± 13.5 years) and 15 controls (15 men, 42.4 ± 11.2 years) were enrolled. LP variations were investigated at five body positions using high-resolution ambulatory monitoring electrocardiography (HR-ambulatory ECG). The HR-ambulatory ECG was recorded for 3 hours and LP parameters (fQRSd, LAS40, and RMS40) were obtained for at least 15 minutes in each at the supine, left and right lateral decubitus, and prone and sitting positions. Results Determinate LP in the BrS group was significantly abnormal in all positions. Among the five body positions, positive LP were much more frequent in the supine and left and right lateral decubitus positions than in the prone and sitting positions and normalized in the last two positions in patients with BrS. RMS40 variance by postural change was significantly larger in the coved group than in the saddle back group. Determinate LP improved in the sitting position compared to the supine position in the coved group. Conclusions Positive LP findings normalized in the sitting position in patients in the coved BrS group with a resuscitation history, suggesting that depolarization instability might be related to the risk of fatal ventricular arrhythmia. Posture-induced LP variance should be examined using HR-ambulatory ECG analysis in patients with BrS.

BackgroundThe important role played by intestinal bacterial flora in human health has recently attracted public attention worldwide. Although yogurt is thought to help in preventing the onset of gastroenteritis, this property has rarely been examined in epidemiological studies.MethodThis study analyzed data obtained by the Japan Environment and Children's Study. From a dataset of 103,062 pregnancies, 82,485 were selected for this analysis. Dietary intake of fermented foods (yogurt and cheese) in 1-year-old infants was assessed with a food frequency questionnaire. Parent-reported physician-diagnosed gastroenteritis in early childhood was determined from a questionnaire conducted when the child was 1 year old.ResultThe incidence of gastroenteritis was significantly lower in infants who consumed yogurt ≥ 7 and 3-6 times/week than in infants who consumed yogurt < 1 time/week in crude models (n = 82,485) and after adjustment for covariates (adjusted odds ratio [95% confidence interval], 0.78 [0.70-0.86] versus 0.82 [0.76-0.89], respectively; n = 65,051). Frequency of weekly cheese consumption was not associated with the incidence of gastroenteritis.ConclusionConsumption of yogurt, but not cheese, at 1 year of age was associated with a reduced risk of gastroenteritis. Further studies of this association, including interventional studies, are warranted.

Oxaliplatin is a first‐line treatment for colorectal cancer. However, shortly following treatment, cold‐evoked hypersensitivity appears in the extremities and over time, the pain is such that oxaliplatin dosing may need to be markedly reduced or even terminated. There is currently a lack of efficacious treatments for oxaliplatin‐induced peripheral neuropathy, which is due in part to the difficulty in translating findings obtained from preclinical rodent models of chemotherapy‐induced peripheral neuropathy. Nonhuman primates (NHP) are phylogenetically closer to humans than rodents and may show drug responses that parallel those of humans. A significant decrease in tail withdrawal latency to 10°C water (“cold hypersensitivity”) was observed beginning 3 days after intravenous infusion of oxaliplatin (5 mg/kg) in Macaca fascicularis. A single treatment of duloxetine (30 mg/kg, p.o.) ameliorated oxaliplatin‐induced cold hypersensitivity, whereas pregabalin (30 mg/kg, p.o.) and tramadol (30 mg/kg, p.o.) did not. By contrast, in rats, no significant cold hypersensitivity, or increased responsiveness to acetone applied to the hind paws, was observed 3 days after the first injection of oxaliplatin (5 mg/kg, i.p., once per day, two injections). Therefore, rats were tested after six treatments of oxaliplatin, 17 days after the first treatment. All analgesics (30 mg/kg, p.o.) significantly ameliorated cold hypersensitivity in rats. The activity of analgesics in the oxaliplatin‐treated macaques parallel clinical findings. The current results indicate that the NHP could serve as a bridge species to improve translatability of preclinical findings into clinically useful treatments for oxaliplatin‐induced peripheral neuropathy.

We investigated photoinduced electron accumulation in a colloidal system of layered hexaniobate that is known as a photocatalytically active wide band-gap semiconductor, and attempted to control the photoresponse by introducing additives into the colloid. The inorganic nanosheets were obtained by exfoliation of the layered oxide. UV-irradiation of the colloids led to electron accumulation in the nanosheets to generate reduced niobate species. Propylammonium ions introduced as the exfoliating reagent and present as the counter ions of niobate nanosheets were indicated as the electron donor that stabilized the electron-accumulating state. Yield and half-life of the reduced niobate species greatly increased by adding an appropriate amount of photochemically inert clay nanosheets, while they increased only a little by the addition of molecular electron donors such as EDTA and triethanolamine. Moreover, the molecular species diminished the enhancement effect of the clay nanosheets. The results suggested that the photochemical event was not explained by direct interactions between the semiconductor nanosheets and the additives at molecular level but governed by indirect interactions between the colloid components regulated by the colloid structure.

Background and objectives: Oxidized HDL (oxHDL) may behave as proinflammatory HDL because of reduced anti-inflammatory capacity and is considered a risk factor for mortality in patients on maintenance hemodialysis (MHD). The study presented here assessed the effect of oxHDL on protein-energy wasting (PEW) in MHD patients. Design, setting, participants, & measurements: This prospective study examined a cohort of MHD patients (n = 176) who were not taking lipid-lowering drugs. Blood samples were obtained to measure albumin, lipids, high-sensitivity C-reactive protein (hsCRP), oxidized LDL (oxLDL), and oxHDL. PEW was assessed by subjective global assessment (SGA) and geriatric nutritional risk index (GNRI). Measurements and assessment of nutritional status were followed up 1 year later. Results: OxHDL was significantly increased in patients with PEW at baseline. High oxHDL and high hsCRP were significantly associated with PEW, and receiver operating characteristic curves for oxHDL and hsCRP showed statistically similar accuracy for predicting SGA-positive status. According to multivariate regression models, high oxHDL had a significant influence on PEW in patients, particularly those with high hsCRP. Decreased changes in GNRI and high prevalence of SGA-positive status at 1 year were more common in patients with high oxHDL at baseline and 1 year later than in patients with low oxHDL at both time points. Conclusions: A high oxHDL state may be associated with PEW estimated by GNRI and SGA, particularly concomitant with inflammation in MHD patients.

Autoimmune inner ear disease (AIED) is a clinical syndrome of uncertain etiology. We present the neuro-otological findings of 2 cases of bilateral hearing loss, dizziness and the antibody profiles of the inner ears. Case 1 had bilateral progressive hearing loss, vestibular dysfunction and abnormal eye movement as the disease progressed. She had inner ear antibodies against 42 and 58kDa protein antigency on Western blot immune assay, and responded to glycocorticosteroid but not to immunosuppressant treatment. Intratympanic steroid injection temporally eliminated her symptoms. However, she developed idiopathic Cushing's syndrome and underwent labyrinthectomy. Case 2 became deaf as a teenager and experienced dizziness 10 years after becoming deaf. He reacted strongly to 68kDa protein and was a good responder to immunosuppressant with steroid. As we still lack a definitive diagnostic test for AIED, careful observation of the clinical course is critical for differential diagnosis regarding the bilateral progressive hearing loss.

Levels of fibroblast growth factor (FGF) 23, a phosphatonin, are frequently elevated in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (MHD). However, the role of FGF23 remains unclear because renal FGF receptor function might be impaired. The present cross-sectional study examines a cohort of patients (n = 196) on MHD who were not undergoing therapy with lipid-lowering drugs including sevelamer. Non-fasting venous blood samples were withdrawn before the hemodialysis (HD) session on the third day after the previous HD session to measure serum levels of albumin, calcium (Ca), phosphate (P), alkaline phosphatase, intact parathyroid hormone (PTH), total cholesterol (C), high-density lipoprotein (HDL)-C, low-density lipoprotein(LDL)-C, oxidative LDL-C, high-sensitivity C-reactive protein (HsCRP), interleukin-6 (IL-6), and FGF23. Nutritional status was assessed using the geriatric nutritional risk index (GNRI). Carotid intima-medial thickness (CIMT) was assessed using a B-mode ultrasound scanner. FGF23 was positively correlated with P, Caalb×P product, and intact PTH, and inversely correlated with C and non-HDL-C. In the higher FGF23 tertile, levels of both non-HDL-C and C were significantly decreased and CIMT was less elevated compared to the lower FGF23 tertile. Multivariate analysis showed that the higher FGF23 tertile was independently associated with decreases in C (adjusted r2 = 0.14) and non-HDL-C (adjusted r2 = 0.20) levels and with a less-pronounced increase in CIMT (adjusted r2 = 0.14). High FGF23 appears to be an independent biomarker of a decrease in C and non-HDL-C that is negatively associated with atherosclerosis in patients on MHD.

【目的】透析患者を対象として，虚血性心疾患（IHD）の存在が患者のメンタルヘルスに及ぼす影響について検討した．【対象・方法】昭和大学病院の関連施設で治療中の維持透析患者50名を対象とした．メンタルヘルスの指標はSF-36v2.0の下位尺度8項目の中からMental health（MH）scoreにて，うつ症状はCenter for Epidemiologic Studies-Depression（CES-D）Scaleにて検討した．これらの検査と同時期の週初め透析前に患者背景の調査，各種血液検査を施行した．【結果】IHD群はnon-IHD群と比較して，高い糖尿病罹患率，高感度CRP値を認めた．さらに，IHD群はnon-IHD群と比較し，MH scoreの有意な低下を認めた．またIHD群は，統計学的有意差はないもののnon-IHD群と比較し高いCES-D scoreを認めた．ステップワイズ重回帰分析を行った結果，IHDの存在がMH scoreに対する有意な説明変数となった（p＜0.05，標準化回帰係数＝－0.308）．【結論】以上の結果から，IHDの存在は透析患者のメンタルヘルスにも影響を及ぼす可能性が示唆された．

In this paper, the authors propose the product planning business model A-POST, which captures the customers tastes exactly and reflects them in the styling design of a product. Specifically, the authors have created a new product design concept using the text mining method which analyzes customers opinions in a language state. As an example of the application of this research, the authors applied this method to the product design process of a new scooter and obtained the results shown.

The paralyzed arytenoid is not immobile and is subjected to passive movement during phonation. If anatomical changes during inspiration and phonation are compared by three-dimensional computed tomography (3D CT), it is possible to observe vertical movement of the paralyzed arytenoid. Our aim was to use 3D CT to examine the characteristics of 3D arytenoid movement in unilateral vocal fold paralysis (UVFP). This is a prospective study. A total of 61 patients (18 females and 43 males) with UVFP who had undergone 3D CT imaging between April 2005 and January 2007 were included. Cricoid and arytenoid cartilage was imaged by 3D CT. We detected the movements of the paralyzed side when comparing inspiration and phonation. The degree of cranial displacement of the paralyzed arytenoids was classified into three grades (I for mild to III for severe). The mean flow rate (MFR) was calculated for each grade. By comparing the MFR of each grade with the normal control group, we determined whether cases would worsen according to grade. Passive gliding movement of the paralyzed arytenoids was found in 90.7% of cases. In all cases, the paralyzed arytenoids were displaced cranially compared to the unaffected side. MFR worsened significantly as the grade became more severe. We believe that the passive gliding movements observed when comparing inspiration and phonation are characteristic of paralysis. Even in mild cases, the paralyzed arytenoids are passively displaced cranially during phonation, and the degree of this displacement is one indicator that can be used to evaluate the severity of UVFP.

Benign paroxysmal positional vertigo (BPPV) is usually idiopathic, but in some cases, it arises after inner ear disease. We examined the cases with and without BPPV-like symptoms in sudden deafness (SD), Meniere's disease (MD) and vestibular neuritis (VN). The equilibrium function tests (caloric test, VEMP and SVV) results were not different between the groups with or without BPPV-like symptoms, but hospitalization was needed more frequently in cases with BPPV-like symptoms. The posterior semicircular canal (PSC) is the most frequent focus of both idiopathic BPPV and BPPV-like symptoms after inner ear disease. The recovery period from vertigo was longer in the cases with BPPV-like symptoms. The effect of physical therapy for the PSC type was equally favorable in cases with idiopathic BPPV and those with inner ear disease associated with BPPV-like symptoms. For the lateral semicircular canal (LSC) type, the effect was less pronounced in cases with idiopathic BPPV. Occurrence of BPPV-like symptoms associated with inner ear disease is possibly caused by the canalolithiasis induced by utricular disturbances.

We report the familial occurrence of bronchiolitis obliterans (BO) associated with pulmonary aspergillosis. A mother and daughter admitted for dyspnea after taking Sauropus androgynus both had overfiltration of both lungs in chest X-ray and severe obstructive impairment in lung function tests. They were initially diagnosed with severe asthma and treated with high-dose prednisolone (0.5mg/kg/day) for 1 month to no effects. They did not show reversibility in lung function test. They were difinitively diagnosed with BO associated with Sauropus androgynus. Six months later, the mother's symptoms worsened with productive sputum and severe dyspnea, and her chest X-ray showed patty shadow in both upper lung fields. Precipitating antibodies to aspergillus antigen were positive and aspergillus fumigatus was detected from her sputum culture. She was diagnosed with aspergillosis and treatment with Micafungin (MCFG) and Itraconazole (ITCZ) was started. The daughter's symptoms also worsened and her chest tomography showed multiple cavities in both lung fields. Precipitating antibodies to aspergillus were positive. She was diagnosed with Invasive aspergillosis. She was treated unsuccessfully with MCFG and Amphotericin B (AMPH) and ITCZ. Few reports cover BO with aspergillus infection without organ impairment. In these 2 cases, treatment with steroids' or immune suppression of the lung with BO may a trigger aspergillus infection.

Anti-HLA antibodies reportedly exist in the one third of pregnant women. But few occurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibodies have been reported. Here a male baby, who was admitted for low birth weight with Down syndrome (DS), was suffered from thrombocytopenia without transient myeloproliferative disorder (TMD). Positive reactions of HLA-specific antibodies were detected in maternal serum. Cross-matching tests between maternal serum and paternal platelets and lymphocytes were strongly positive. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-A2 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented. This is the first case of DS with NAIT due to anti-HLA antibodies.

The shoulder and elbow joint of a baseball pitcher are frequently overused by the repetition of throwing. The overuse causes throwing injuries of the shoulder or the elbow joint. To prevent the injuries or find them as soon as possible at an early stage, it is important to understand and evaluate each individual’s baseball pitching motion exactly. Therefore, we are developing an analysis system of the baseball pitching motion for clinical use.The pitching motion is classified into four major pitch styles, as follows: overhand, three-quarter, sidearm, and underhand. In the long-term clinical experience in Nobuhara Hospital, we have expected that one of the causes of throwing injuries is related to the pitch styles. A previous paper reported that different pitch styles produced different kinematic and kinetic results of pitching motion analysis (Matsuo, 2000). The difference of pitch styles will influence analysis results of the pitching motion.The classification, however, was performed qualitatively by a person having baseball experience. There is no standard method to classify the pitch styles quantitatively. The pitch styles also have to be classified quantitatively in order to investigate various factors of injuries. The aim of this study was to classify baseball pitchers of various levels into four pitch styles quantitatively and compare the kinematic and kinetic parameters.We measured the pitching motions of the baseball pitchers, using a motion-capture system at 500 Hz. Ages of the 104 subjects of this experiment ranged from 10 to 38 years. We suggested four kinematic parameters in order to classify the pitch styles. The measured pitching motions were then classified into four pitch styles, using multivariate discriminant analysis. The correct answer rate was 89.4%.ANOVA revealed significant differences of the antero-posterior direction of resultant force at the time of ball release among four classified pitch styles. The A-P force vector had high correlation (r=0.82) with horizontal adduction angle of the upper arm. The shear force on the shoulder is one of causes of injury during pitching. To reduce the risk of shoulder injuries, we believe it is necessary to reduce shear forces on the pitcher’s shoulder. Our results showed that the sidearm group had 50% lower shear force than the other groups.In conclusion, we suggested four kinematic parameters in order to classify the pitch styles. This result shows that these parameters are appropriate for classifying the pitch styles without relation to age or skill differences. The results of kinematic and kinetic parameters showed the significant differences between four pitch styles. Our next task is to increase the number of subjects, especially sidearm and underhand pitchers.

The role of salt intake in the development of hypertension is prominent, but its mechanism has not been fully elucidated. Our aim was to examine the effect of transient salt intake during the prehypertensive period in hypertensive model animals. Dahl salt-sensitive rats and spontaneously hypertensive rats were fed from 6 to 14 weeks with low-salt (0.12% NaCl), normal-salt (0.8% NaCl), high-salt (7% NaCl), or high-sodium/normal-chloride diet and returned to normal-salt diet for 3 months. Rats in the high-salt group saw elevations in blood pressure (BP) not only during the treatment period but also for the 3 months after returning to normal-salt diet. We named this phenomenon salt memory. Renal arteriolar injury was found in the high-salt group at the end of experiment. Dahl salt-sensitive rats were fed from 6 to 14 weeks with high-salt diet with angiotensin receptor blocker, vasodilator, calcium channel blocker, and calcium channel blocker+angiotensin receptor blocker and returned to normal-salt diet. Although BP was suppressed to control levels by vasodilator or calcium channel blocker, elevated renal angiotensin II and renal arteriolar injury were observed, and salt memory did not disappear because of sustained renal arteriolar injury. Calcium channel blocker+angiotensin receptor blocker suppressed renal arteriolar injury, resulting in the disappearance of salt memory. Cross-transplantation of kidneys from Dahl salt-sensitive rats on high salt to control rats caused increase of BP, whereas control kidneys caused reduction in BP of hypertensive rats, inducing the central role of the kidney. These results suggest that renal arteriolar injury through BP and renal angiotensin II elevation plays important roles in the development of salt memory for hypertension.

It is well known that a certain population of cells in the primary visual cortex shows direction selective responses to visual stimuli. Physiological studies suggest that an interaction of excitatory responses and intracortical inhibition play an essential role in this selectivity. In this paper, neural network models of the direction-selective cell consisting of both excitatory subsystems and feedforward lateral inhibitory subsystems are proposed. In these models, direction selectivity is produced as a result of the nonlinear interaction of both subsystems. When only the inhibitory subsystem is weakened, the interaction cannot occur properly and direction selectivity disappears. These models thus show the characteristic disappearance of direction selectivity, similar to that found in physiological experiments on the behavior of the direction-selective cells caused by blockade of the cortical inhibition. These models can organize direction-selective receptive fields with Hebb-like learning rules when inhibitory subsystems are properly controlled to balance both subsystems.

In this paper, the author proposes a systematic approach to visualizing the progress of business processes (changes in people, goods, information, and costs) and seeks to build A-BPNS (Ama-lab’s Business Process Navigation System), a diagnostic system that enables the timely implementation of the necessary measures. Case studies are presented covering general business in research and manufacturing development and design, where the system has been applied with significant results.

In order to estimate the penetration depth of transdermal 3% GA MHPh 2Na-10% lidocaine gel mixture, the following physiological functions of the skin were examined before and after a 60 min occulusive application of the gel in 16 adult volunteers. Thermal sweat expulsins ceased completely on the gel-treated ventral surface of one forearm in all the firs 5 subjects, though it continued on the untreated contrast area of the other forearm. Sympathetic skin response (SSR) was also no longer induced on the gel-treated middle finger in 1 of another 3 subjects and was severely depressed in the other 2 subjects, while the SSR on the untreated index finger appeared constantly. Vasomotion of the skin circulation on another 3 subjects, remained unaffected on both the gel-treated and the untreated fingers. Extraction of a leg-hair in the treated area did not induce pain sensation in all the last 5 subjects. In addition to the transcellular main roots, some of the transcutaneously applied gel seems to penetrate deeply into the skin through the appendageal roots such as the eccrine sweat glands and the pilosebaceous glands.

Currently, knowledge within the field of software development is largely implicit and is not formally disseminated and shared. This means that there is little improvement and regeneration of processes, and knowledge gained from previous projects is not necessarily applied to new ones. In order to turn this situation around it is necessary to take an organized approach to sharing job-related information. For this study, the authors constructed Amalab Project Planning Navigation System “A-PPNS”, a system for organizing accumulated knowledge related to the field of software development. More specifically, A-PPNS is a business process monitoring system and consists of the following four elements: (i) Optimized estimate support subsystem, (ii) Schedule monitoring system, (iii) QCD optimization diagnostic system, and (iv) Strategic technology accumulation system. The effectiveness of this system has been demonstrated and verified at Company A, a system integration company.

Chordal injection of autologous fat is useful in treating incomplete closure of the glottis on phonation, because it is simple, uses an intraoral approach and is mostly effective. However, when excess fat is injected, the removal of the excess is generally much more difficult than the injection. A 48-year-old man underwent intrachordal injections of autologous fat twice bilaterally for vocal fold atrophy. He came to our hospital because his hoarseness became worse after every operation. Three-dimensional computed tomography revealed that a large amount of fat was injected in the bilateral subglottal and glottic regions. These findings indicated that his dysphonia was due mainly to the excessive injected fat, and removal of the fat was planned. Under local anesthesia, we partially removed the excess fat through a window made in the thyroid cartilage, without touching the vocal folds. The voice and laryngeal findings were monitored during the surgery according to fiber-stroboscopic findings. Postoperatively, a significant improvement was seen in the voice and vibration of the vocal folds, although the results were not completely satisfactory.