NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

Upward-directed exit-site of the swan-neck catheter and "Easy-to-disinfect the backside area of exit-site" may prevent PD complications.

BACKGROUND: Upward-directed exit-site has been believed to be the worst for frequent ESI by an old retrospective study using straight catheters. No comparison study of 3 exit-site directions using swan-neck catheter has been performed regarding which direction is the best for our endpoints, Easy-to-see the backside area of exit-site: ESBE, Easy-to-disinfect the backside area of exit-site: EDBE, reduction of both exit-site infection (ESI), symptomatic catheter dislocation and peritonitis. METHODS: We assessed the relationship of exit-site direction with our endpoints in a quantitative cross-sectional, multicentered questionnaire survey. Patients who received either non-surgical catheter implantation or exit-site surgery were excluded. RESULTS: The numbers (percentage) of exit-site directions in included 291 patients were upward 79 (26.0), lateralward 108 (37.5) and downward 105 (36.5). Cochran-Armitage analysis showed a significant step-ladder increase in the prevalence of ESI as the direction changed from upward to lateralward to downward (0.15 ± 0.41, 0.25 ± 0.54, 0.38 ± 0.69 episodes/patient-year, p = 0.03). Multivariable regression analysis revealed the upward exit-site independently associates with both higher frequency of ESBE (OR 5.55, 95% CI 2.23-16.45, p < 0.01) and reduction of prevalence of ESI (OR 0.55, 95%CI 0.27-0.98, p = 0.04). Positive association between the prevalence of symptomatic catheter dislocation and ESI (OR 2.84, 95% CI 1.27-7.82, p = 0.01), and inverse association between EDBE and either prevalence of symptomatic catheter dislocation (OR 0.27, 95% CI 0.11-0.72) or peritonitis (OR 0.48, 95% CI 0.23-0.99) observed. CONCLUSION: Upward-directed swan-neck catheter exit-site may be the best for both ESBE and prevention of ESI. EDBE may reduce catheter dislocation and peritonitis. Symptomatic catheter dislocation may predict ESI.

Study protocol and baseline characteristics of newly induced dialysis patients: a prospective multi-center cohort study with a biological sample bank, the Ibaraki Dialysis Initiation Cohort (iDIC) study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) face higher risks of life-threatening events including cardiovascular disease. Various risk factors are identified as agents influencing the life prognosis of ESKD patients. Herein, we evaluated the risk factors related to the outcomes of Japanese patients with dialysis induction. We present the study protocol, the patients' baseline characteristics, and their outcomes. METHODS: The Ibaraki Dialysis Initiation Cohort (iDIC) Study is a prospective multi-center cohort study in collaboration with 60 tertiary-care facilities in Ibaraki Prefecture, Japan. We collected baseline data from clinical records and analyzed blood and urine samples of these facilities' patients with diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis (CGN). The study's primary outcome was the survival rate at 24 months after dialysis induction. We performed a Kaplan-Meier analysis for cumulative survival and a Cox proportional hazards analysis for all-cause mortality and hospitalization. RESULTS: We analyzed 636 patients' cases (424 males, 212 females, age 67.4 ± 13.1 yrs. [mean ± SD]). We compared the patients' baseline data with those of similar cohort studies. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 (15.9%) as hypertensive nephrosclerosis, and 114 (17.9%) as CGN. The mean serum creatinine value was 9.1 ± 2.9 mg/dL. The mean estimated glomerular filtration rate was 5.6 ± 1.8 mL/min/1.73m2. The cumulative survival rates at 6 months and 24 months after dialysis induction were 95.2 and 87.7%, respectively. The cumulative survival rate was significantly lower with increasing age. A Cox proportional hazards regression analysis demonstrated that high age was significantly associated with all-cause mortality. CONCLUSIONS: Regarding the clinical characteristics of these newly induced dialysis patients, the same trend as in other cohort studies was observed. Another study is underway to explore prognostic factors based on the iDIC Study's findings.

Bioaccumulation Patterns of Perfluoroalkyl Acids in an Estuary of the Ariake Sea, Japan.

To evaluate the bioaccumulation potential of perfluoroalkyl acids (PFAAs) in an aquatic food web, we measured the concentrations of nine PFAAs in the water and aquatic organisms from an estuary of the Omuta River, Japan. Average log bioaccumulation factors for all PFAAs ranged from 2.0 to 2.8. There was no positive correlation observed between PFAA carbon chain length and there was no evidence of trophic magnification demonstrated among the sample types collected. These results differed from the findings of previous studies in enclosed bodies of water, perhaps because river mouth-estuarine ecotones are more variable spatially and temporally and include some fish that are highly migratory. Further investigations of bioaccumulation factors will be needed to elucidate the tendency of amphiphilic chemicals to bioaccumulate in these river mouth-estuarine ecotones.

Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors.

Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.

Urinary phosphorus excretion per creatinine clearance as a prognostic marker for progression of chronic kidney disease: a retrospective cohort study.

BACKGROUND: Whether phosphate itself has nephrotoxicity in patients with chronic kidney disease (CKD) is controversial, although phosphate excretion into urine may cause tubular damage in rat models. To evaluate actual phosphate load on each nephron, we examined the association between 24-h urinary phosphorus excretion per creatinine clearance (24-h U-P/CCr), a newly proposed index that is a surrogate for nephron load, and CKD progression in patients with CKD. METHODS: We conducted a single-center, retrospective cohort study. To avoid potential confounders for protein intake, only patients on our educational program for CKD with a fixed diet regimen and aged 20 years or older were included. The observation period was 3 years. Primary outcomes were CKD progression defined as a composite of end-stage kidney disease (ESKD) or 50 % reduction of estimated glomerular filtration rate. Patients were stratified by quartiles of 24-h U-P/CCr levels as Quartiles 1-4. The association was examined in three models: unadjusted (Model 1), adjusted for risk factors for CKD progression (Model 2), and factors that affect renal phosphate handling (Model 3). RESULTS: A total of 191 patients met the eligibility criteria. Patients with higher 24-h U-P/CCr showed a higher risk for the composite outcomes. The hazard ratios [95 % confidence interval] for 24-h U-P/CCr levels in Quartile 2, 3, and 4, respectively, versus Quartile 1 were 2.56 (1.15-6.24), 7.53 (3.63-17.62), and 12.17 (5.82-28.64) in Model 1; 1.66 (0.63-4.97), 3.57 (1.25-11.71), and 5.34 (1.41-22.32) in Model 2; and 3.07 (0.97-11.85), 7.52 (2.13-32.69), and 7.89 (1.74-44.33) in Model 3. CONCLUSIONS: Our study showed that higher phosphorus excretion per creatinine clearance was associated with CKD progression.

[Successful steroid therapy for indolent myeloma with kidney injury due to direct infiltration of myeloma cells].

A 68-year-old woman visited JA Toride Medical Center with asymptomatic proteinuria. Bence Jones protein-λ was identified in her serum and urine samples, and subsequent bone marrow aspiration revealed multiple myeloma (MM). Simultaneous renal biopsy showed only minor glomerular abnormality and preserved interstitium. Since the clinical stage was not advanced, aggressive treatment was avoided. During the following six months, her renal function gradually deteriorated with sustained elevation of urine protein and ß2 microglobulin excretion, although other routine blood tests yielded stable results. In contrast to the first renal biopsy, the second biopsy specimen exhibited findings suggestive of inflammatory cell infiltration associated with light chain deposition along the tubular basement membrane. However, her myeloma did not cause symptoms other than mild renal disorder and remained in the category of indolent myeloma. Therefore a moderate dose of steroid therapy according to the regimen of common interstitial nephritis was initiated and her renal function and urinary findings partially recovered. Subsequently, her condition was diagnosed as infiltration of plasma cells with positive λ-light chain deposition. Since direct infiltration of myeloma cells into the renal interstitium rarely causes renal failure especially at the initial stage, we did not conduct intensive chemotherapy with possible severe side effects. More intensive chemotherapy would have been administered if the patient had suffered from other organ damage. There are no reports of cases in whom steroid alone was effective against multiple myeloma, hence this case is of clinical significance in providing a treatment option for renal dysfunction caused by restricted infiltration of myeloma cells, especially for cases where intensive chemotherapy is contraindicated.

Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: HS219 (40 mg chitosan-loaded chewing gum) is designed to bind salivary phosphorus as an add-on to available phosphorus binders. We performed a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis (HD) patients with hyperphosphatemia as an add-on to phosphorus binders. METHODS: Sixty-eight HD patients who were maintained on calcium carbonate (n=33) or sevelamer hydrochloride (n=35) were enrolled. The primary end point was a change in serum phosphorus levels. Secondary end points included changes in levels of salivary phosphorus, serum calcium, parathyroid hormone (PTH), and intact fibroblast growth factor (iFGF) 23. RESULTS: Sixty-three patients chewed either HS219 (n=35) or placebo (n=28) for 30 min, three times a day, for 3 weeks. HS219 was well tolerated and safe. However, HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period. There were no significant effects of HS219 on reduction of salivary phosphorus, serum calcium, iPTH, or iFGF23 levels. CONCLUSIONS: The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia. Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT01039428, 24 December, 2009.

Evaluation of Scissor Glide Characteristics Through Surgeons' Subjective Assessment: The Application of Nitriding in Scissor Hardening Tests.

INTRODUCTION: In robotic surgery, studies on providing tactile feedback to users are ongoing. However, the accuracy of the subjective sensations of surgeons, as users, has been largely unassessed. This study aimed to assess the validity of surgeons' subjective evaluations of scissors resistance through interindividual, inter-surgeon, and objective evaluations. Furthermore, in this study, we explored the possibility of using nitriding to increase the hardness of the scissors and assessed changes in subjective resistance values before and after nitriding using this approach. METHOD: Five surgeons conducted validation of five curved surgical scissors (145 mm; Arakawa Seisakujyo Co., Ltd., Tokyo, Japan) and assessed their subjective resistance using a scale from 0 to 10, where a rating of 10 signified significant resistance impeding the scissors' closure. The temporal changes in subjective resistance values, from maximum open to close, were graphically recorded. To demonstrate the reproducibility of subjective resistance values, the subjective resistance values of the same control scissors were measured at intervals of at least two weeks, and the correlation coefficient was calculated. To analyze the closing characteristics of subjective resistance values between different pairs of scissors, the effect of scissor type and scissor closure position was compared as two independent variables using a two-factor analysis of variance. A comparative evaluation was conducted to assess the frictional properties of scissors after nitriding, comparing the subjective assessment by surgeons with the objective assessment using a digital force gauge. RESULTS: The correlation coefficient of subjective resistance values measured by surgeons demonstrated a high reproducibility of 0.746. A two-factor analysis of variance conducted on subjective resistance values demonstrated the presence of a primary effect for the sample factor (scissors), as well as for the position factor (closing process), with the additional observation of the interaction between these two factors. The results from the two-factor analysis of variance above provide evidence supporting the validity of the subjective resistance measurements. There was a significant increase in subjective resistance after the nitriding process. The graph of subjective resistance values and objective resistance values showed similarity. CONCLUSIONS: The surgeons' subjective assessment of scissors resistance showed high reproducibility and validity, as evidenced by distinguishable differences in scissor movement interactions and pre- and post-nitriding resistance. Further studies are warranted to expand on these findings.

Noninvasive total counting of cultured cells using a home-use scanner with a pattern sheet.

The inherent variability in cell culture techniques hinders their reproducibility. To address this issue, we introduce a comprehensive cell observation device. This new approach enhances the features of existing home-use scanners by implementing a pattern sheet. Compared with fluorescent staining, our method over- or underestimated the cell count by a mere 5%. The proposed technique showcased a strong correlation with conventional methodologies, displaying R2 values of 0.91 and 0.99 compared with the standard chamber and fluorescence methods, respectively. Simulations of microscopic observations indicated the potential to estimate accurately the total cell count using just 20 fields of view. Our proposed cell-counting device offers a straightforward, noninvasive means of measuring the number of cultured cells. By harnessing the power of deep learning, this device ensures data integrity, thereby making it an attractive option for future cell culture research.

A Low Mean Closing Load and a Decrease in Load Change at the Tip Increase the Comfort of Scissors.

Introduction During surgery, surgeons intuitively recognize when they are using dull scissors and find them difficult to use. The purpose of this study was to objectively evaluate the physical characteristics of scissors and the comfort reported by surgeons to develop objective quality control standards for scissors used in surgery. Methods Sensory and measurement tests were conducted to evaluate the comfort and physical characteristics of ten pairs of Cooper scissors. As a sensory test, thirty-one volunteer surgeons opened and closed the scissors and selected three that felt comfortable and three that were uncomfortable. The results were scored. For measurement, a load was applied to the handle of the scissors. The load pressure and displacement of the width between each handle when the scissors were closed were measured. Results A strong negative correlation was found between the total comfort score and the mean load value between sensory and measurement tests (r=-0.717, p=0.0195). The correlation between the total score and the change in load at the tip showed a moderate negative correlation (r=-0.687, p=0.0282). Multiple regression analysis showed that the change in load at the tip was an independent factor affecting the total score. Conclusions Surgeons consider scissors with a low mean load required to close the scissors and a small change in load at the tip to be comfortable. The mean load on scissors and the change in load at the tip should be considered in the development of quality control standards for scissors used in surgery.

The association of very-low-density lipoprotein with ankle-brachial index in peritoneal dialysis patients with controlled serum low-density lipoprotein cholesterol level.

BACKGROUND: Peripheral artery disease (PAD) represents atherosclerotic disease and is a risk factor for death in peritoneal dialysis (PD) patients, who tend to show an atherogenic lipid profile. In this study, we investigated the relationship between lipid profile and ankle-brachial index (ABI) as an index of atherosclerosis in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level. METHODS: Thirty-five PD patients, whose serum LDL cholesterol level was controlled at less than 120 mg/dl, were enrolled in this cross-sectional study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions and the mean size of lipoprotein particles were measured using an improved method, namely, high-performance gel permeation chromatography. Multivariate linear regression analysis was adjusted for diabetes mellitus and cardiovascular and/or cerebrovascular diseases. RESULTS: The mean (standard deviation) age was 61.6 (10.5) years; PD vintage, 38.5 (28.1) months; ABI, 1.07 (0.22). A low ABI (0.9 or lower) was observed in 7 patients (low-ABI group). The low-ABI group showed significantly higher cholesterol proportions in the chylomicron fraction and large very-low-density lipoproteins (VLDLs) (Fractions 3-5) than the high-ABI group (ABI>0.9). Adjusted multivariate linear regression analysis showed that ABI was negatively associated with serum VLDL cholesterol level (parameter estimate=-0.00566, p=0.0074); the cholesterol proportions in large VLDLs (Fraction 4, parameter estimate=-3.82, p=0.038; Fraction 5, parameter estimate=-3.62, p=0.0039) and medium VLDL (Fraction 6, parameter estimate=-3.25, p=0.014); and the size of VLDL particles (parameter estimate=-0.0352, p=0.032). CONCLUSIONS: This study showed that the characteristics of VLDL particles were associated with ABI among PD patients. Lowering serum VLDL level may be an effective therapy against atherosclerosis in PD patients after the control of serum LDL cholesterol level.

Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography.

BACKGROUND: Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. METHODS: Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). RESULTS: Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). CONCLUSIONS: HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin.

Baseline characteristics and prevalence of cardiovascular disease in newly visiting or referred chronic kidney disease patients to nephrology centers in Japan: a prospective cohort study.

BACKGROUND: About 39,000 patients were newly prescribed renal replacement therapy in Japan in 2011, resulting in a total of more than 300,000 patients being treated with dialysis. This high prevalence of treated end stage kidney disease (ESKD) patients is an emergent problem that requires immediate attention. We launched a prospective cohort study to evaluate population specific characteristics of the progression of chronic kidney disease (CKD). In this report, we describe the baseline characteristics and risk factors for cardiovascular disease (CVD) prevalence among this cohort. METHODS: New patients from 16 nephrology centers who were older than 20 years of age and who visited or were referred for the treatment of CKD stage 2-5, but were not on dialysis therapy, were recruited in this study. At enrollment, medical history, lifestyle behaviors, functional status and current medications were recorded, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by a modified three-variable equation. RESULTS: We enrolled 1138 patients, 69.6% of whom were male, with a mean age of 68 years. Compared with Western cohorts, patients in this study had a lower body mass index (BMI) and higher proteinuria. The prevalence of CVD was 26.8%, which was lower than that in Western cohorts but higher than that in the general Japanese population. Multivariate analysis demonstrated the following association with CVD prevalence: hypertension (adjusted odds ratio (aOR) 3.57; 95% confidence interval (CI) 1.82-7.02); diabetes (aOR 2.45; 95% CI 1.86-3.23); hemoglobin level less than 11 g/dl (aOR 1.61; 95% CI 1.21-2.15); receiving anti-hypertensive agents (aOR 3.54; 95% CI 2.27-5.53); and statin therapy (aOR 2.73; 95% CI 2.04-3.66). The combination of decreased eGFR and increased proteinuria was also associated with a higher prevalence of CVD. CONCLUSIONS: The participants in this cohort had a lower BMI, higher proteinuria and lower prevalence of CVD compared with Western cohorts. Lower eGFR and high proteinuria were associated with CVD prevalence. Prospective follow up of these study patients will contribute to establishment of individual population-based treatment of CKD.

[Successful maintenance hemodialysis therapy with supplemented growth hormone in a diabetic patient with growth hormone insufficiency].

Growth hormone (GH) insufficiency is difficult to identify especially in adults, because its clinical manifestations overlap with metabolic syndrome and diabetes mellitus. We experienced a case of a 38-year-old woman who abruptly gained weight from the age of five, and was diagnosed as type 2 diabetes mellitus (DM) during her 20s. When the patient visited JA Toride Medical Center at age 38, her renal function had been severely damaged, and caused congestive heart failure. Hemodialysis (HD) therapy was introduced, and GH insufficiency was identified, based on her obesity profile since her childhood and hormone surveillance. GH supplementation was initially avoided, because of her concurrent problems of DM and advanced renal failure. However, because of her restricted activities in daily living (ADL) and frequent hypotension episodes, a decision was taken to start supplementary administration of GH, which consequently succeeded in stabilizing blood pressure and extended her ADL. Although GH supplementation has recently been reported to be effective in improving protein energy malnutrition in dialysis patients without GH insufficiency, there is no report concerning GH insufficiency in dialysis patients. This is the first case report of GH insufficiency, in which GH supplementation enabled the patient to continue HD.

The effect of refresher training on fact description in medical incident report writing in the Japanese language.

To maintain the effectiveness of the training (1st-Training Session: 1st-TS) to accurate describe facts in the medical incident reports (IRs) in Japanese, a refresher TS was designed and its effectiveness was examined. First, textual analysis showed that IRs' accuracy significantly decreased six months after the 1st-TS. Based on this result, the refresher TS was designed and conducted with 64 residents. To verify the refresher TS' effectiveness, IRs after the 1st-TS, six months later, and after the refresher TS were compared via text analysis. The results showed that the refresher TS restored the description rate of patient's background, safety check procedures, original work procedures, information on equipment used, reporter's actions, and post-incident response. The questionnaire was also administered and showed that the refresher TS contributed to residents' motivation to learn about IRs. In conclusion, the refresher TS contributed to sustaining the effect of the 1st-TS on accurately describing IRs.

Case of hereditary kidney disease presenting thin basement membrane with a single heterozygous variant of Intersectin 2.

Objective: Intersectin 2 (ITSN2) is reported to cause hereditary nephrotic syndrome, but the number of cases remains quite small. We observed a case of progressive renal dysfunction and family history for end-stage kidney disease with a known single heterozygous ITSN2 variant. This study aimed to reveal the novel pathological significance of altered ITSN2 expression via a detailed examination. Patient and Methods: A 52-year-old Japanese woman with mild proteinuria and hematuria visited our center. The patient did not opt for a detailed examination but was instead followed up with conservative treatment consisting of low-dose angiotensin receptor blockers. Serum Cr worsened from 1.15 to 1.79 mg/dL after 7 years when precise diagnosis was performed by renal biopsy and genetic testing. Results: Kidney biopsy showed a thin basement membrane (TBM) and global glomerulosclerosis in 37.5% (6 out of 16) glomeruli examined. Comprehensive gene panel testing of 121 genes revealed a known ITSN2 variant, assumed to be involved in pathogenesis. No variants in the Alport syndrome genes, which are typically responsible for TBM, were detected. Conclusion: A possible novel phenotype of the heterozygous ITSN2 variant was identified as a cause of hereditary renal failure. Further investigation of similar cases is required for a better understanding.

Central diabetes insipidus with anti-rabphilin-3A antibody positivity causing hypovolemic shock after resection of tumorous lesions in the pelvic cavity.

A 36-year-old female was pointed out to have liver enzyme elevation by routine health checkup. Subsequent contrast-enhanced CT scan identified gigantic uterine fibroids and retroperitoneal tumor. She was referred to the gynecologist at JA Toride Medical Center and planned to undergo a uterus enucleation and biopsy of the retroperitoneal tumor. The surgery was conducted without any troubles. After the surgery, the patient presented polyuria with urine volume 10-20 L a day and developed hypovolemic shock. Laboratory test revealed hypotonic urine and hypernatremia. Arginine vasopressin (AVP) loading test suggested shortage of endogenous vasopressin. Since the subcutaneous administration of AVP was not sufficient to control the urine volume, continuous intravenous infusion of AVP was initiated. After achieving hemodynamic stability, the treatment was switched to oral desmopressin. MRI finding indicated attenuation of high signal in posterior pituitary in T1 weighted image while neither enlargement of pituitary nor thickening of pituitary stalk was indicated by enhanced MRI. Hypertonic salt solution test indicated no responsive elevation of AVP, confirming the diagnosis of central diabetes insipidus (CDI). Her anterior pituitary function was preserved. Only anti-rabphilin-3A antibody was found positive in the serum of the patient, while other secondary causes for CDI were denied serologically and radiologically. Hence, lymphocytic infundibuloneurohypophysitis　(LINH) was suspected as the final diagnosis. Hormonal replacement therapy by nasal desmopressin was continued and the patient managed to control her urine volume. In cases of CDI considered idiopathic with conventional examinations, anti-rabphilin-3A antibody may be a clue for determining the cause as LINH.

Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors.

BACKGROUND: Developing a screening method for identifying individuals at higher risk of elevated brain amyloid burden is important to reduce costs and burden to patients in clinical trials on Alzheimer's disease or the clinical setting. We developed machine learning models using objectively measured lifestyle factors to predict elevated brain amyloid burden on positron emission tomography. METHODS: Our prospective cohort study of non-demented, community-dwelling older adults aged ≥ 65 years was conducted from August 2015 to September 2019 in Usuki, Oita Prefecture, Japan. One hundred and twenty-two individuals with mild cognitive impairment or subjective memory complaints (54 men and 68 women, median age: 75.50 years) wore wearable sensors and completed self-reported questionnaires, cognitive test, and positron emission tomography imaging at baseline. Moreover, 99 individuals in the second year and 61 individuals in the third year were followed up. In total, 282 eligible records with valid wearable sensors, cognitive test results, and amyloid imaging and data on demographic characteristics, living environments, and health behaviors were used in the machine learning models. Amyloid positivity was defined as a standardized uptake value ratio of ≥ 1.4. Models were constructed using kernel support vector machine, Elastic Net, and logistic regression for predicting amyloid positivity. The mean score among 10 times fivefold cross-validation repeats was utilized for evaluation. RESULTS: In Elastic Net, the mean area under the receiver operating characteristic curve of the model using objectively measured lifestyle factors alone was 0.70, whereas that of the models using wearable sensors in combination with demographic characteristics and health and life environment questionnaires was 0.79. Moreover, 22 variables were common to all machine learning models. CONCLUSION: Our machine learning models are useful for predicting elevated brain amyloid burden using readily-available and noninvasive variables without the need to visit a hospital. TRIAL REGISTRATION: This prospective study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of Oita University Hospital (UMIN000017442). A written informed consent was obtained from all participants. This research was performed based on the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

Production of marmoset eggs and embryos from xenotransplanted ovary tissues.

The common marmoset (Callithrix jacchus) has attracted attention as a valuable primate model for the analysis of human diseases. Despite the potential for primate genetic modification, however, its widespread lab usage has been limited due to the requirement for a large number of eggs. To make up for traditional oocyte retrieval methods such as hormone administration and surgical techniques, we carried out an alternative approach by utilizing ovarian tissue from deceased marmosets that had been disposed of. This ovarian tissue contains oocytes and can be used as a valuable source of follicles and oocytes. In this approach, the ovarian tissue sections were transplanted under the renal capsules of immunodeficient mice first. Subsequent steps consist of development of follicles by hormone administrations, induction of oocyte maturation and fertilization, and culture of the embryo. This method was first established with rat ovaries, then applied to marmoset ovaries, ultimately resulting in the successful acquisition of the late-stage marmoset embryos. This approach has the potential to contribute to advancements in genetic modification research and disease modeling through the use of primate models, promoting biotechnology with non-human primates and the 3Rs principle in animal experimentation.