Association Between Nonadherence and Transient Hyperuricemia in Pediatric Kidney Transplantation.

BACKGROUND: Nonadherence among pediatric transplant recipients is a significant problem that reduces graft survival and leads to poor kidney graft outcomes. It is, however, extremely difficult to detect during a regular follow-up. This study, therefore, aimed to investigate the risk factors involved in nonadherence, focusing on unexplained transient hyperuricemia in pediatric kidney transplant (KTx) recipients at a single pediatric center. METHODS: This retrospective study included 167 patients who underwent KTx at our pediatric center. A Cox proportional hazards analysis was performed to evaluate the risk of nonadherence using the following factors: age, sex, body mass index SD score, transient hyperuricemia, hypertension, and follow-up period. RESULTS: Nonadherence was identified in 19 patients (11%), with the average (SD) age and post-KTx duration at diagnosis being 17.21 (4.73) years and 79.21 (38.77) months, respectively. Thirty-four patients (20%) were diagnosed with transient hyperuricemia at a median of 14 months after KTx. On multivariate Cox regression analysis, transient hyperuricemia was the only independent risk factor for nonadherence after KTx. CONCLUSIONS: Transient hyperuricemia was identified as one of the risk factors for nonadherence after KTx; therefore, careful monitoring for transient hyperuricemia may allow early detection of nonadherence.

IMPACT ON ABSORBED DOSE RATE IN AIR IN KANTO REGION BY FUKUSHIMA DAIICHI NUCLEAR POWER PLANT ACCIDENT.

Absorbed dose rates in air were measured for the whole area of the Kanto region in 2015, 2016 and 2017 (n = 31 147). The mean absorbed dose rates in air for each prefecture measured by car-borne surveys were from 44 to 67 nGy h-1 (13-289 nGy h-1). The absorbed dose rate in air from artificial radionuclides (134Cs + 137Cs) measured by fixed-point observation (n = 507) was from 1 to 14 nGy h-1 (0-105 nGy h-1), and meaning that the contribution ratios of 134Cs and 137Cs were 3-22%. The deposited location of artificial radionuclides was less than 1000 m from ground level and depended on the topography, wind direction and precipitation field.

Microscopic gain analysis of modulation-doped GeSn/SiGeSn quantum wells: epitaxial design toward high-temperature lasing.

Threshold carrier densities of GeSn quantum well (QW) lasers and the physical reason of low-temperature lasing of current GeSn laser are investigated through the comparison of threshold carrier densities of conventional III-V QW lasers. Electrons distributed over L-band is the main cause of decreased gain for GeSn QWs. To increase the gain (and improve the laser characteristics), a modulation-doped GeSn QW is proposed and the material gain is analyzed based on many-body theory for both qualitative and quantitative simulation. Significant gain increase can be expected for n-type modulation doping QWs. The doping condition for elevated temperature lasing is discussed and it was found that material gain curve similar to III-V QW is obtained for GeSn QW with n-type modulation doping of 6 × 1018 cm-3. It was also found that unlike III-V QW lasers, n-type modulation doping is more effective for high-speed operation in terms of differential gain than p-type modulation doping.

Randomized phase III and extension studies: efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer.

BACKGROUND: The efficacy and safety of naldemedine (a peripherally acting µ-opioid receptor antagonist) for opioid-induced constipation (OIC) in subjects with cancer was demonstrated in the primary report of a phase III, double-blind study (COMPOSE-4) and its open-label extension (COMPOSE-5). The primary end point, the proportion of spontaneous bowel movement (SBM) responders, was met. Here, we report results from secondary end points, including quality of life (QOL) assessments from these studies. PATIENTS AND METHODS: In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 97) or placebo (n = 96) for 2 weeks, and those who continued on to COMPOSE-5 received naldemedine for 12 weeks (n = 131). Secondary assessments in COMPOSE-4 included the proportion of complete SBM (CSBM) responders, SBM or CSBM responders by week, and subjects with ≥1 SBM or CSBM within 24 h postinitial dose. Changes from baseline in the frequency of SBMs or CSBMs per week were assessed at weeks 1 and 2. Time to the first SBM or CSBM postinitial dose was also evaluated. In both studies, QOL impact was evaluated by Patient Assessment of Constipation-Symptoms (PAC-SYM) and PAC-QOL questionnaires. RESULTS: Naldemedine improved bowel function for all secondary efficacy assessments versus placebo (all P ≤ 0.0002). The timely onset of naldemedine activity versus placebo was evidenced by median time to the first SBM (4.7 h versus 26.6 h) and CSBM (24.0 h versus 218.5 h) postinitial dose (all P < 0.0001). In COMPOSE-4, significant differences between groups were observed with the PAC-SYM stool domain (P = 0.045) and PAC-QOL dissatisfaction domain (P = 0.015). In COMPOSE-5, significant improvements from baseline were observed for overall and individual domain scores of PAC-SYM and PAC-QOL. CONCLUSIONS: Naldemedine provided effective and timely symptomatic relief from OIC and improved the QOL of subjects with OIC and cancer. TRIAL REGISTRATION ID: www.ClinicalTrials.jp: JAPIC-CTI-132340 (COMPOSE-4) and JAPIC-CTI-132342 (COMPOSE-5).

Identification of an argpyrimidine-modified protein in human red blood cells from schizophrenic patients: A possible biomarker for diseases involving carbonyl stress.

Argpyrimidine (ARP) is an advanced glycation end product thought to be generated from a reaction between methylglyoxal and arginine residues in proteins. In this study, we observed marked accumulation of an approximately 56 kD protein, reactive to anti-ARP antibodies, in the red blood cells (RBCs) of some patients with refractory schizophrenia. This ARP-modified protein was purified from the blood of schizophrenic patients and identified as selenium binding protein 1 (SBP1) by LC-MS/MS. This is the first report of ARP-modified proteins accumulating in RBCs of patients with diseases involving carbonyl stress. We also observed high accumulation of ARP-modified SBP1 in the RBCs of patients with chronic kidney disease. Therefore, this modified protein may be a novel marker of carbonyl stress.

Patching retinal breaks with Seprafilm for treating retinal detachments in humans: 9 years of follow-up.

PurposeTo describe the long-term surgical outcomes of four patients treated for retinal detachment using Seprafilm as a novel technique.MethodsRetinal breaks in four eyes were covered with Seprafilm using a transvitreal approach after cataract surgery, pars plana vitrectomy, fluid-air exchange, and laser photocoagulation. Neither long-standing gas nor silicone oil was used. The patients were not instructed to maintain a specific head positioning postoperatively.ResultsSuccessful retinal reattachment was achieved with a single surgery in all four eyes, and none developed proliferative vitreoretinopathy. The mean best-corrected visual acuity preoperatively and 9 years postoperatively were 20/97 and 20/33, respectively. The intraocular pressure increased several days postoperatively that lasted no longer than 2 weeks. Visual field defects either in the inferonasal or inferotemporal quadrant were detected postoperatively. The mean electroretinogram a- and b-wave amplitude ratios of the operated eyes to the fellow eyes were 0.68 and 0.64 preoperatively and 0.87 and 0.92 postoperatively, respectively. The mean corneal endothelial cell density was 2365 cells/mm2 preoperatively and 2592 cells/mm2 postoperatively.ConclusionCovering retinal breaks with Seprafilm may promote retinal reattachment without gas tamponade and postoperative head positioning. The visual outcomes 9 years postoperatively showed no apparent adverse effects of intraocular application of Seprafilm.

High-resolution copy number variation analysis of schizophrenia in Japan.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Cancer emerging from the recurrence of sessile serrated adenoma/polyp resected endoscopically 5 years ago.

Since the serrated neoplastic pathway has been regarded as an important pathway of colorectal carcinogenesis, few reports have been published on clinical cases of cancer derived from sessile serrated adenoma/polyp, especially on recurrence after resected sessile serrated adenoma/polyp. An elderly woman underwent endoscopic mucosal resection of a flat elevated lesion, 30 mm in diameter, in the ascending colon; the histopathological diagnosis at that time was a hyperplastic polyp, now known as sessile serrated adenoma/polyp. Five years later, cancer due to the malignant transformation of the sessile serrated adenoma/polyp was detected at the same site. The endoscopic diagnosis was a deep invasive carcinoma with a remnant sessile serrated adenoma/polyp component. The carcinoma was surgically removed, and the pathological diagnosis was an adenocarcinoma with sessile serrated adenoma/polyp, which invaded the muscularis propria. The surgically removed lesion did not have a B-RAF mutation in either the sessile serrated adenoma/polyp or the carcinoma; moreover, the initial endoscopically resected lesion also did not have a B-RAF mutation. Immunohistochemistry confirmed negative MLH1 protein expression in only the cancer cells. Lynch syndrome was not detected on genomic examination. The lesion was considered to be a cancer derived from sessile serrated adenoma/polyp recurrence after endoscopic resection, because both the surgically and endoscopically resected lesions were detected at the same location and had similar pathological characteristics, with a serrated structure and low-grade atypia. Furthermore, both lesions had a rare diagnosis of a sessile serrated adenoma/polyp without B-RAF mutation. This report highlights the need for the follow-up colonoscopy after endoscopic resection and rethinking our resection procedures to improve treatment.

A randomized controlled trial comparing a prepackaged low-residue diet with a restricted diet for colonoscopy preparation: the impact on the results of colonoscopy in adenoma detection.

AIM: This study aimed to investigate the clinical utility of a prepackaged low-residue diet (PLD) compared with a restricted diet (RD) for colonoscopic bowel preparation. METHOD: A prospective randomized controlled trial was carried out with patients undergoing colonoscopy. One hundred patients were randomly assigned to PLD and RD groups. In the RD group, the patients received an information sheet containing acceptable low-residue options and instructions from the medical staff. All patients received 10 ml sodium picosulphate the day before colonoscopy and 1 l of polyethylene glycol with ascorbic acid (PEG-A) on the day of the colonoscopy. If the bowel preparation was not adequate, an additional PEG-A solution was given. The primary outcome was the efficacy of colonic cleansing as rated by the Boston Bowel Preparation Scale (BBPS). The additional amount of PEG-A solution, adenoma detection rate and patient tolerance were assessed as secondary outcomes. RESULTS: The BBPS score in the PLD group was 7.3 ± 1.7 compared with 6.5 ± 1.7 in the RD group. The quality of bowel preparation was significantly better in the PLD group (P < 0.05). The mean amount of additional PEG-A solution in the PLD group was smaller than in the RD group (293.8 ± 474.8 vs 444.1 ± 625.0 ml), but there was no statistical difference between the two groups. Adenoma detection rates and patient tolerance were similar in the two groups. CONCLUSION: Prepackaged low-residue diets PLD is superior to RD for bowel preparation for colonoscopy.

Hepatitis E virus infection and acute-on-chronic liver failure in West Africa: a case-control study from The Gambia.

BACKGROUND: In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF). AIMS: To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa. METHODS: We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls. RESULTS: In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality. CONCLUSIONS: Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia.

Spin-dependent acoustic response in the nonunitary A1 and A2 phases of superfluid 3He under high magnetic fields.

The transverse acoustic impedance of superfluid ^{3}He was measured in the A1 and A2 phases up to 13 T to investigate the surface states in nonunitary superfluids. The temperature dependence of the impedance was much larger in the A1 phase than in the A2 phase. This nonsymmetric behavior indicates that momentum exchange with walls for spin-down surface states is quite different from that for spin-up surface states. The spin-dependent response might be a reflection of an essential feature of the nonunitary states where gap amplitudes depend on spin states. Weak-coupling theories ignore any spin-dependent processes and do not account for the nonsymmetric behavior.

Electroencephalogram measurement from the hairy part of the scalp using polymer-based dry microneedle electrodes.

This paper reports a successful electroencephalogram (EEG) measurement from the hairy part of the scalp using a polymer-based dry microneedle electrode. The electrode consists of 25 pillars, each of which has a sharp microneedle on the top. Hairs are collected into the gaps of the pillars and the microneedles can reach the scalp surface. Since the microneedles can penetrate through the stratum corneum, no conductive gel is necessary to acquire high quality EEG. We experimentally investigated the pillar diameters in EEG measurement from the occipital region with hairs. The fabricated electrodes successfully measured EEG without any skin preparation or conductive gel.

Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B.

The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.

Selective ß2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement.

Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. ß2-Adrenergic receptor (ß2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that ß-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via ß2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific ß2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via ß2-AR blocking.

Infrared evidence of a Slater metal-insulator transition in NaOsO3.

The magnetically driven metal-insulator transition (MIT) was predicted by Slater in the fifties. Here a long-range antiferromagnetic (AF) order can open up a gap at the Brillouin electronic band boundary regardless of the Coulomb repulsion magnitude. However, while many low-dimensional organic conductors display evidence for an AF driven MIT, in three-dimensional (3D) systems the Slater MIT still remains elusive. We employ terahertz and infrared spectroscopy to investigate the MIT in the NaOsO3 3D antiferromagnet. From the optical conductivity analysis we find evidence for a continuous opening of the energy gap, whose temperature dependence can be well described in terms of a second order phase transition. The comparison between the experimental Drude spectral weight and the one calculated through Local Density Approximation (LDA) shows that electronic correlations play a limited role in the MIT. All the experimental evidence demonstrates that NaOsO3 is the first known 3D Slater insulator.

Clinical outcomes of endoscopic resection for nonampullary duodenal high-grade dysplasia and intramucosal carcinoma.

This study retrospectively analyzed the clinical outcomes of endoscopic resection of 26 sporadic (i. e., not associated with polyposis syndrome) nonampullary duodenal lesions representing high-grade dysplasia or intramucosal carcinoma (duodenal HGD/IMC) in 23 patients. No severe complications such as perforation were observed, but three cases of delayed bleeding were seen. The use of endoscopic clips significantly decreased the delayed bleeding rate (0/19, 0%) compared with cases in which clips were not used (3/7, 42.9%; P = 0.013, χ2 test). Eighteen lesions (69.2%) were removed by en bloc resection. The follow-up period after resection was 25.5 ± 23.3 months. Two lesions (7.7%) that recurred locally were detected at the first surveillance endoscopy 3 months after resection. These lesions were 22 and 15 mm in size respectively and were resected piecemeal. Endoscopic resection is an effective and safe procedure for treating duodenal HGD/IMC. En bloc resection and prophylactic clip usage are encouraged.

Concomitant use of enteral nutrition therapy is associated with sustained response to infliximab in patients with Crohn's disease.

BACKGROUND/OBJECTIVES: A significant proportion of Crohn's disease (CD) patients receiving infliximab (IFX) maintenance therapy show loss of responsiveness despite a good initial response. The factors other than immunomodulators that prevent IFX dose escalation have yet to be fully elucidated. This study was performed to identify clinical factors or concomitant therapies associated with sustained response to IFX. SUBJECTS/METHODS: Seventy-four consecutive CD patients who had successful IFX induction therapy between 2002 and 2010 underwent IFX maintenance therapy. Patients showing loss of response to IFX were treated with IFX intensification therapy. Factors involved in the sustained response to IFX were investigated retrospectively. RESULTS: After a median follow-up of 85 weeks, loss of response to IFX was observed in 30 (40.5%) cases. On logistic regression analysis, concomitant use of enteral nutrition (EN) therapy (elemental and/or polymeric formulas) was identified as an independent factor associated with sustained response to IFX. Receiver operating characteristic curve analysis indicated a cutoff value of 600 kcal/day. We divided the patients into the 'EN group' (≥ 600 kcal/day) and 'control group' (<600 kcal/day). The cumulative number of loss of response was significantly lower in the EN group (odds ratio: 0.23, P = 0.0043). Kaplan-Meier analysis confirmed the significantly lower rate of loss of response in the EN group (P = 0.013). Multivariate hazard ratio was 0.37 (P = 0.025). Type of EN formula did not affect the results. CONCLUSIONS: Concomitant use of EN ≥ 600 kcal/day is likely to yield a sustained response to IFX in CD patients.

Predictive factors of response to intravenous ciclosporin in severe ulcerative colitis: the development of a novel prediction formula.

BACKGROUND: When treating patients with severe ulcerative colitis (UC), accurate prediction of drug efficacy contributes to early clinical decision-making. AIM: To identify predictive factors and to develop a reliable prediction formula and a decision tree of response to intravenous ciclosporin treatment for severe UC. METHODS: Patients included in this study were those diagnosed with refractory severe UC who had undergone ciclosporin treatment between December 2004 and March 2011 at a tertiary referral centre in Japan. Demographic and clinical parameters from all patients were analysed by multivariate statistics. RESULTS: Fifty-two patients were included in this study (36.5% men with an average age of ciclosporin initiation of 40.2 ± 15.6 years). Thirty-four patients (65.4%) were responders to the treatment with ciclosporin and avoided colectomy, 18 patients (34.6%) were nonresponders and underwent colectomy. Stepwise multiple logistic regression analysis identified four independent predictive factors of response to intravenous ciclosporin: age at hospitalisation (AGE), platelet count (×10(4) /µL) on the first day (PLA), Lichtiger score on the third day (LIC) and total protein (g/dL) on the third day minus total protein on the first day (ΔTP). The calculation formula (8.5 - 0.16 × AGE + 0.21 × PLA - 0.61 × LIC + 2.3 × ΔTP < 0) predicted colectomy with an accuracy of 88.5% and the decision tree predicted colectomy with an accuracy of 90.4%. CONCLUSION: The novel calculation formula and the decision tree effectively predict the clinical outcome of ciclosporin treatment for severe ulcerative colitis as early as on day 3 after starting ciclosporin treatment.