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Hirotaka Fukami, Yoichi Takeuchi, Saeko Kagaya, Yoshie Ojima, Ayako Saito, Hiroyuki Sato, Ken Matsuda, Tasuku Nagasawa Department of Nephrology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi Prefecture, Japan Purpose: Pyelonephritis, an upper urinary tract infection, is a serious infection that often requires hospitalization. However, the accurate diagnosis of acute pyelonephritis can be difficult, especially among older individuals who can present with unusual symptoms. Imaging with computed tomography (CT) is not unusual in the diagnosis of pyelonephritis, with some clinicians regarding perirenal fat stranding (PFS) as a characteristic finding. However, the sensitivity and specificity of PFS in diagnosing pyelonephritis are currently unknown. We therefore sought to clarify the relevance of PFS in diagnosing acute pyelonephritis.Patients and methods: We conducted a case-controlled retrospective analysis of medical records. The pyelonephritis group included 89 patients who had been diagnosed with acute pyelonephritis, while the control group included 319 patients who had undergone percutaneous renal biopsy. CT findings were available for both groups. The frequency of PFS and its sensitivity and specificity for the diagnosis of acute pyelonephritis were investigated.Results: The mean ages of the pyelonephritis and control groups were 74±15 years and 63±16 years, respectively. A total of 28% of men were in the pyelonephritis group vs 61% of men in the control group. The frequency of PFS was 72% in the pyelonephritis group vs 39% in the control group. Age and renal dysfunction were associated with an increased frequency of PFS. After adjusting for age, sex, and renal function using a propensity score analysis, the sensitivity, specificity, and positive likelihood ratio of PFS for diagnosing acute pyelonephritis were 72%, 58%, and 1.7, respectively.Conclusion: The presence of PFS was not useful in diagnosing acute pyelonephritis. Keywords: acute pyelonephritis, perirenal fat stranding, sensitivity, specificity, urinary tract infection, CT

Fukami H, Takeuchi Y, Kagaya S, et al. Int J Gen Med. 2017;10:137–144.Page 137, Abstract, Results, the text “The frequency of PFS was 72% in the pyelonephritis group vs 39% in the control group” should read “The frequency of PFS was 72% in the pyelonephritis group vs 29% in the control group”.Page 140, Table 1, Control (PRB) column, last row, the data “93 (39%)” should read “93 (29%)”.Page 141, Discussion, line 5, the text “PFS was found in 39% of patients” should read “PFS was found in 72% of patients”. Read the original article

Retail prices for eggs surged during the period from early 2022 to mid-2023 in the U.S. We investigate the impact of egg price fluctuations on online and social media discourse, analyzing the relationship between egg prices and public sentiment. Utilizing online and social media listening data from September 2019 to August 2023, we explore how the total number of statements (i.e., mentions) and sentiment respond to changes in egg prices in the U.S. We find a significant association between increases in egg prices and both the volume of mentions and the sentiment of online discussions. Notably, mentions increased and sentiment became more negative as egg prices rose, highlighting a clear public response to price changes. However, the relationship between egg prices and online and social media attention is complex, which becomes apparent when studying the timing of increased concern with the timing of online news media coverage. Importantly, using regression discontinuity in time, we show that online and social media conversations about eggs and egg prices tend to increase after the rapid rise in online news coverage. Similarly, online and social media conversations about eggs and egg prices tend to decrease after the rapid rise in online news coverage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Nicole Widmar reports financial support was provided by USDA National Institute of Food and Agriculture, Hatch Project 7007883. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Curved varus osteotomy (CVO) is an effective femoral head-preserving surgical procedure for osteonecrosis of the femoral head (ONFH) classified as type B or C1 according to the Japanese Investigation Committee (JIC) classification; it reportedly provides better postoperative outcomes than transtrochanteric rotational osteotomy (TRO). We have developed a new procedure called spherical varus rotational osteotomy (SVRO) in which osteotomy of the femur into a spherical shape is followed by varus and anterior rotation using navigation to increase indications and improve postoperative outcomes., Methods: Nine joints of eight patients who underwent SVRO and could be followed up for > 1 year were included in the study. Disease types determined preoperatively according to the JIC classification were type C1 for four joints and type C2 for five joints. Preoperative disease JIC classification stages were 3a for eight joints and 1 for one joint. SVRO was performed using OrthoMap ® 3D Navigation software, and the following variables were measured: surgery time, intraoperative blood loss, difference between preoperative and postoperative angles of anteversion, postoperative lower limb length discrepancy, and postoperative intact area occupancy. The Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) was used for clinical evaluation. Visual Analog Scale and JHEQ scores were evaluated preoperatively and at the final follow-up., Results: The measurement results were as follows: surgery time, 130 min; blood loss, 200 ml; angle of varus, 20°; angle of anterior rotation, 30°; preoperative angle of anteversion, 15°; postoperative angle of anteversion, 22°; lower limb shortening, 11 mm; preoperative intact area occupancy, 0%; and postoperative intact area occupancy, 74.2%. There were no cases of progression in the postoperative stages or re-collapse., Conclusion: SVRO allows for the repositioning of the exterior and posterior intact areas, providing a broader intact region postoperatively. This technique is particularly beneficial for young patients with ONFH and extensive necrosis and is a less invasive alternative to TRO. This procedure has been shown to be effective in achieving favorable outcomes in patients with extensive necrosis who would have otherwise required rotational osteotomy, depending on the necrosis location. Further longitudinal studies are necessary to validate these findings and establish long-term benefits., (© 2024. The Author(s).)

An automated system for the rapid separation and preconcentration of trace elements was developed. Carboxymethylated polyethyleneimine 600 (CM-PEI600), which is a partially carboxymethylated polyethyleneimine with a molecular weight of 600 Da, was used as a chelating resin to quantitatively recover trace elements under high-flow-rate conditions. For accurately and precisely determining trace elements, even with a rough control of the sample and eluent flow volumes, an internal standardization technique was employed for the solid-phase extraction and separation. A recovery test of the deionized water-based sample solution was conducted using this system, and good results, with a recovery of 92% or higher, were obtained for 11 elements (Cd, Co, Cu, Fe, Mn, Mo, Ni, Pb, Ti, V, and Zn). Eight elements present in certified groundwater and wastewater reference materials (ES-L-1 and EU-L) were separated and preconcentrated using this system. Almost all the determined values were within their tolerance intervals, and no significant differences were observed between the determined and certified values, demonstrating the validity of this method. The time required for the separation and preconcentration using approximately 100 mL of the sample solution was approximately 6.5 min, and theoretically, the system could be used to preconcentrate 17 samples in an hour because extraction and elution could be conducted simultaneously using two cartridges packed with the chelating resin. Using this system equipped with cartridges packed with CM-PEI600 resin, solid-phase extraction and the separation of multiple elements were performed simultaneously, automatically, and rapidly, enabling the accurate and precise determination of trace elements in environmental water and inorganic salts even by rapidly flowing the sample solutions using peristaltic pumps. Compared to NOBIAS Chelate PA-1, a commercially available chelating resin, the CM-PEI600 resin can recover trace elements even under an extremely high flow rate of approximately 50 mL min -1 ., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

The secretory glycoprotein lactoferrin (LF) is suggested to ameliorate overweight regardless of non-genetic or genetic mechanisms. Although maternal overweight represents a key predictor of offspring growth, the efficacy of LF on fertility problems in overweight and obese mothers remains unknown. To address this issue, we examined the effect of LF ingestion by analyzing overweight mice (Institute of Cancer Research (ICR) mice with high-fat diets; HF mice) and obese mice ( leptin -deficient mice with type II diabetes; ob/ob mice). Plasma insulin, leptin, glucose, and cholesterol levels were measured, and thermal imaging and histological analysis were employed. The litter size of HF females was reduced due to miscarriage, which was reversed by LF ingestion. In addition, LF ingestion suppressed overweight prevalence in their offspring. The component analysis of the maternal blood demonstrated that glucose concentration in both HF females and their offspring was normalized by LF ingestion, which further standardized the concentration of insulin, but not leptin. LF ingestion was unable to reverse female infertility in ob/ob mice, although their obesity and uterine function were partially improved. Our results indicate that LF upregulates female fertility by reinforcing ovarian and uterine functions in females that are overweight due to caloric surplus.

Internal standardization was applied to the solid-phase extraction of trace elements using the following commercially available aminocarboxylic acid-type chelating resins: InertSep ME-2, NOBIAS Chelate PA-1, and Presep PolyChelate. The concentration of the trace elements in initial sample solution can be calculated by using the ratio of the added amount of the internal standard element, Y, in the initial sample solution to that in the final solution after the solid-phase extraction, which is proportional to the volume of the sample solution passed through the cartridge, and the ratio of the volume of the initial sample solution to that of a blank solution for preparing the calibration curve. In this solid-phase extraction, strict control of the volumes of the sample solution passed through the cartridge and the final solution after the solid-phase extraction is not needed because these are not used in the calculation of the trace element concentration. The solid-phase extraction with the internal standardization using Y could be applied to the separation and preconcentration of some trace elements, namely Cd, Co, Cu, Fe, Ni, Pb, Ti, and Zn in an artificial seawater spiked with the elements and some certified reference materials, EnviroMAT ES-L-1 Ground Water and EU-L-3 Waste Water, without any interference.

Background: A catheter fragment with inaccessible ends can be retrieved using the well-known two-step method: making a free end with a pigtail catheter and seizing it with a snare catheter. Here we propose an easier and faster modification, named the "pigtail through snare" technique., Case Presentation: A 61-year-old female patient underwent removal of a central venous catheter fragment migrating to the right atrium. Both ends located in the right atrial appendage and left hepatic vein were inaccessible. Initially, a snare loop was opened in the inferior vena cava and a pigtail catheter was advanced through the snare loop to hook the catheter fragment. The free end was created by pulling the pigtail catheter, dragged automatically into the snare loop, grasped, and retrieved immediately., Conclusions: By passing the pigtail catheter through the snare loop in advance, the snaring maneuver becomes easy and fast in retrieving the catheter fragment with inaccessible ends.

Oxaliplatin (OXL) therapy often causes side effects including chronic peripheral neuropathy. We investigated the pain-relieving effects of recombinant human lactoferrin (rhLf) as well as a long-acting IgG-Fc fused rhLf (rhLf-Fc) on OXL-induced neuropathic pain. We used the hLf in this study, because the homology between mouse Lf and hLf is higher than that of bovine Lf. In addition, rhLf-Fc is expected to enhance the analgesic effect due to the life extension effect in the body. We administered OXL (2 mg/kg, i.v.) to mice twice weekly for 4 weeks. Phosphate buffered saline (PBS), rhLf (100 mg/kg, i.p.) or rhLf-Fc (100 mg/kg, i.p.) was administered once a week from day 15 to 32. We also assessed the continuous infusion of same drugs (10 mg/kg/day) into the external jugular vein by using an osmotic pump. Both of rhLf and rhLf-Fc significantly reduced the hypersensitivity to mechanical stimulation when they were administered intraperitoneally. The continuous infusion of rhLf resulted in a more pronounced effect. Histopathological analysis of sciatic nerve showed that both rhLf and rhLf-Fc tended to reduce nerve fiber damage, but no significant difference was observed in nerve fiber cross-sectional area. Therefore, it was suggested that rhLf or rhLf-Fc injection could be an option for controlling neuropathic pain, which are side effects of OXL.

To study the size-resolved characteristics of airborne bacterial community composition, diversity, and abundance, outdoor aerosol samples were analysed by 16S rRNA gene-targeted quantitative PCR and amplicon sequencing with Illumina MiSeq. The samples were collected using size-resolved samplers between August and October 2016, at a suburban site in Toyama City and an urban site in Yokohama City, Japan. The bacterial communities were found to be dominated by Actinobacteria, Firmicutes, and Proteobacteria. At the genus level, we found a high abundance of human skin-associated bacteria, such as Propionibacterium, Staphylococcus, and Corynebacterium, in the urban site. Whereas, a high abundance of bacteria associated with soil and plants, such as Methylobacterium and Sphingomonas, was observed in the suburban site. Furthermore, our data revealed a shift in the bacterial community structure, diversity, and abundance of total bacteria at a threshold of 1.1-µm diameter. Interestingly, we observed that Legionella spp., the causal agents of legionellosis in humans, were mainly detected in > 2.1 µm coarse particles. Our data indicate that local environmental factors including built environments could influence the outdoor airborne bacterial community at each site. These results provide a basis for understanding the size-resolved properties of bacterial community composition, diversity, and abundance in outdoor aerosol samples and their potential influence on human health.

New chelating resins immobilizing carboxymethylated polyallylamine (CM-PAA) were prepared by immobilizing PAAs with some molecular weights on methacrylate resins and then carboxymethylating a part of amino groups in the PAAs using various amounts of sodium monochloroacetate. The molecular weight of PAA barely affected both the amount of PAA immobilized on the resin and the relationship between the carboxymethylation (CM) rate and the ratio of the amount of monochloroacetate used in the CM step. The selectivity of CM-PAA resin for solid-phase extraction of trace elements was almost the same as that of a resin immobilizing carboxylymethylated polyethyleneimine; 10 elements, namely Cd, Co, Cu, Fe, Mo, Ni, Pb, Ti, V, and Zn, could be quantitatively recovered over a wide pH range and alkali and alkaline earth elements were scarcely extracted under acidic and neutral conditions. The CM-PAA resin was applicable to the separation and preconcentration of the elements in a certified reference material (Waste Water, EU-L-1) and a real environmental water sample (ground water).

Three types of transmembrane protein, IRE1α/IRE1β, PERK, and ATF6α/ATF6β, are expressed ubiquitously in vertebrates as transducers of the unfolded protein response (UPR), which maintains the homeostasis of the endoplasmic reticulum. IRE1 is highly conserved from yeast to mammals, and transmits a signal by a unique mechanism, namely splicing of mRNA encoding XBP1, the transcription factor downstream of IRE1 in metazoans. IRE1 contains a ribonuclease domain in its cytoplasmic region which initiates splicing reaction by direct cleavage of XBP1 mRNA at the two stem loop structures. As the UPR is considered to be involved in the development and progression of various diseases, as well as in the survival and growth of tumor cells, UPR inhibitors have been sought. To date, IRE1 inhibitors have been screened using cell-based reporter assays and fluorescent-based in vitro cleavage assays. Here, we used medaka fish to develop an in vivo assay for IRE1α inhibitors. IRE1α, IRE1β, ATF6α and ATF6β are ubiquitously expressed in medaka. We found that IRE1α/ATF6α-double knockout is lethal, similarly to IRE1α/IRE1β- and ATF6α/ATF6β-double knockout. Therefore, IRE1 inhibitors are expected to confer lethality to ATF6α-knockout medaka but not to wild-type medaka. One compound named K114 was obtained from 1,280 compounds using this phenotypic screening. K114 inhibited ER stress-induced splicing of XBP1 mRNA as well as reporter luciferase expression in HCT116 cells derived from human colorectal carcinoma, and inhibited ribonuclease activity of human IRE1α in vitro. Thus, this phenotypic assay can be used as a quick test for the efficacy of IRE1α inhibitors in vivo.Key words: endoplasmic reticulum, inhibitor screening, mRNA splicing, phenotypic assay, unfolded protein response.

Fabry disease (FD) is a rare X-linked hereditary disorder (Xq22) caused by a deficiency in alpha-galactosidase activity. A 34-year-old man was referred to our hospital because of renal dysfunction. He had previously undergone pacemaker implantation at 24 years of age. Investigations revealed undetectable alpha-galactosidase A activity levels. Renal biopsy results indicated vacuolization of podocytes. A genetic analysis revealed that the patient carried the W340X mutation. Enzyme replacement therapy with agalsidase beta was started. This case is novel because most cases of FD nephropathy precede cardiac disease. In our patient, the cardiac event was the initial event, and renal impairment followed.

Chelating resins immobilizing carboxymethylated polyethyleneimine (CM-PEI) with different carboxymethylation rates were prepared. The thermal decomposition behavior of CM-PEI resins was investigated using thermogravimetry-differential thermal analysis/photo ionization-quadrupole mass spectrometry (TG-DTA/PI-QMS) and ion attachment ionization-quadrupole mass spectrometry equipped with direct inlet probe (DIP/IA-QMS). The obtained results suggested that the carboxymethyl group decomposed at relatively low temperature (150 °C - 300 °C); the peak areas at m/z 45 and 59 in TG-DTA/PI-QMS and m/z 58, 70, and 72 in DIP/IA-QMS significantly increased with increasing carboxymethylation rate. These relationships should be useful for estimating the carboxymethylation rate of CM-PEI resin.

Chelating resins immobilizing phosphomethylated polyethyleneimine (PM-PEI) with different phosphomethylation (PM) rates were prepared by using different amounts of both phosphonic acid and paraformaldehyde in the phosphomethylation of PEI immobilized on a methacrylate resin as a base resin. The extraction of many elements improved with increasing PM rate; REEs, Be, Fe, Mo, Ti, and V were quantitatively extracted at pH 2. The elution of the elements tended to become difficult with increasing PM rate. When a PM-PEI resin with a PM rate of 0.26 was used, REEs and Be could be eluted using 0.2 mol L -1 EDTA solution adjusted to a pH of 7 and 3 mol L -1 nitric acid, respectively, although the elution of Fe, Mo, Ti, and V was insufficient. The PM-PEI resin could be reused at least 10 times to recover REEs and Be without the influence of any other elements. The PM-PEI resin could be applied to a recovery test using artificial seawater spiked with REEs, except for Sc, Tm, Yb, and Lu, and the separation of the REEs in NIST SRM 1515 Apple Leaves.

Percutaneous native renal biopsy is recognized as a safe procedure. The majority of bleeding events occur within 24 h after the procedure, and reports of delayed major complications are very limited. We report a patient presenting with sudden flank pain 7 days after renal biopsy, in whom abdominal computed tomography showed increased hematoma size with extravasation and who was treated with radiological intervention. Careful attention should be paid to diagnose and treat delayed major complications in patients undergoing native renal biopsy.

A previously healthy 58-year-old man was admitted for muscle pain and weakness [manual muscle testing (MMT) of 4/4 for upper and lower limbs]. We detected elevated levels of inflammatory makers and PR3-anti-neutrophil cytoplasmic antibody (ANCA). Subsequently, the muscle weakness rapidly progressed to an MMT of 2 for all limbs. Magnetic resonance imaging indicated muscle edema, and the creatine kinase (CK) level increased to 29,998 U/L. Methylprednisolone (mPSL) and cyclophosphamide pulse therapy improved the patient symptoms. MMT recovered to 4 for all limbs. A muscle biopsy showed degenerated muscle fibers surrounded by neutrophil-predominant infiltration. In addition, lamina elastic breakdown and fibrinoid necrosis of arterioles were observed. A final diagnosis of microscopic polyangiitis (MPA) limited to the muscles was made.

Background/aim: Cardiovascular disease is the most serious cause of death in patients on hemodialysis. Low serum magnesium (Mg) and high serum calcium (Ca) levels have been associated with poor outcome and cardiovascular mortality in patients on maintenance and initiation dialysis. As a more accurate marker is warranted, we evaluated the efficacy of a novel serum Ca-Mg marker of all-cause and cardiovascular mortality that indicates vessel calcification., Methods: We recruited 378 consecutive patients with end-stage renal disease who started dialysis between January 2009 and December 2015 at the Japanese Red Cross Ishinomaki Hospital. We collected data of patients' demographic characteristics and comorbidities from their electronic medical records. We retrospectively examined the association of the serum Ca-Mg ratio with all-cause and cardiovascular mortality using the Cox proportional hazard model, and determined the value that predicted cardiovascular death using the receiver operating characteristic (ROC) curve., Results: Overall, 253 patients with serum Mg and Ca data were analyzed. The 3-year survival rate of this group was 0.70 (95% confidence interval [CI] 0.55-0.80), and the hazard ratio for the risk of death was 3.94 (95% CI 1.37-11.31). The 3-year cardiovascular mortality rate was 0.12 (95% CI 0.05-0.23), which was significantly higher than that of the other groups. The ROC curve of cardiovascular mortality with the Ca-Mg ratio was greater than that of Mg (area under the curve 0.75 vs. 0.69, p = 0.037)., Conclusion: A high Ca-Mg ratio was significantly associated with all-cause and cardiovascular mortality, and it was more accurate than serum Mg.

Recrystallization behaviors of water sorbed into four poly(meth)acrylates, poly(2-methoxyethyl acrylate), poly(tetrahydrofurfuryl acrylate), poly(methyl acrylate), and poly(methyl methacrylate), are investigated by variable-temperature mid-infrared (VT-MIR) spectroscopy and molecular dynamics (MD) simulation. VT-MIR spectra demonstrate that recrystallization temperatures of water sorbed into the polymers are positively correlated with their glass-transition temperatures reported previously. The present MD simulation shows that a lower-limit temperature of the diffusion for the sorbed water and the glass-transition temperatures of the polymers also have a positive correlation, indicating that the recrystallization is controlled by diffusion mechanism rather than reorientation mechanism. Detailed molecular processes of not only recrystallization during rewarming but also crystallization during cooling and hydrogen-bonding states of water in the polymers are systematically analyzed and discussed.

Background: Antineutrophil cytoplasmic antibody-associated vasculitis is triggered by environmental factors, including silica dust exposure. Repeated tsunami waves brought a large volume of silica-containing sludge inland after the Great East Japan earthquake in 2011. We aimed to determine if the serious disaster influenced the clinical features of the microscopic polyangiitis., Methods: This is an observational retrospective study conducted in a single institute. A total of 43 patients were included based on the CHCC2012 criteria for microscopic polyangiitis from 2007 to 2015. We used the Poisson regression model to determine the incidence of microscopic polyangiitis within the annual population of the medical district. The participants were selected during a 3-year period from before (N = 13) to after the disaster (N = 20). The differences of parameters and the overall survival between the groups were analyzed., Results: The incidence of microscopic polyangiitis increased after the disaster (λ = 17.4/million/year [95%CI: 7.66-39.6] before the disaster and λ = 33.1/million/year [17.7-61.7] after the disaster, P = 0.044). A high Birmingham Activity Score was associated with a high incidence of microscopic polyangiitis after the disaster. The overall survival of the patients with microscopic polyangiitis declined significantly after the disaster., Conclusions: The Great East Japan earthquake influenced the development of the microscopic polyangiitis in our restricted area. The patients who developed after the disaster had severe symptoms and a high mortality rate.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m 2 /week for 4 weeks (i.e., the conventional lymphoma dosing schedule) is used, but the optimal dosing schedule is controversial. Indeed, a single-dose of RTX successfully controlled nephrotic syndrome. However, to date, the effectiveness of a single RTX dose in treating MPA has not been fully investigated in Japan. This was a retrospective observational study. Six newly diagnosed patients with MPA were initially treated with methylprednisolone and a single dose of RTX (375 mg/m 2 ). We investigated the patients' clinical features, as well as the efficacy and safety of RTX treatment. All patients attained remission on a tapered prednisolone dose of < 10 mg/day during the first 12 months. One patient relapsed after 12 months whereas another required hospitalization owing to infective spondyloarthritis. Adverse reactions to RTX infusion and late-onset neutropenia were not observed. Therefore, a single-dose treatment with RTX induced remission with few complications, and allowed tapering the prednisolone treatment. We conclude that a single dose of RTX is a promising induction therapy for MPA, reducing the cost associated with multiple doses.

Background: The aim of this study was to investigate specific bleeding volume after percutaneous renal biopsy (PRB) and the correlation between bleeding volume and clinical parameters. Methods: A retrospective study of 252 consecutive patients (153 male patients and 99 female patients) who underwent PRB at the Department of Nephrology, Japanese Red Cross Ishinomaki Hospital, between July 2013 and January 2016 was conducted. PRB was performed under ultrasound guidance using an automated spring-loaded biopsy device and a 16-cm, 16-gauge needle. Patients underwent computed tomography (CT) the day after PRB. Bleeding volume after PRB was evaluated using reconstructed CT data. Results: The median bleeding volume after PRB was 38 mL (25th-75th percentile, 18-85 mL), with ≥4 punctures identified as a risk factor for massive bleeding. The incidence rates of macrohematuria, transient hypotension and bladder obstruction were 14.3, 8.7 and 4.7%, respectively. Post-PRB blood transfusion and intervention were required in 4.7 and 0.8% of patients, respectively. Conclusion: Although it is difficult to assess the risk for massive bleeding prior to PRB, we do provide evidence of a specific increased risk with ≥4 puncture attempts, and recommend careful follow-up of these patients.

An important reason for the inefficient extraction of Cr(VI) from its acidic solutions into polymer inclusion membranes (PIMs), consisting of poly(vinyl chloride) as the base-polymer and Aliquat 336 as the carrier, was found to be associated with the leaching of Aliquat 336 from the PIMs into the solutions, where it subsequently reduced the anionic Cr(VI) species to cationic Cr(III) species. The PIM extraction efficiency for Cr(VI) was significantly improved by the addition of NaNO 3 to the solutions, which suppressed the leaching of Aliquat 336 and the reduction of Cr(VI) to Cr(III).

Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Antiestrogen agents are commonly used to treat patients with estrogen receptor (ER)-positive breast cancer. Tamoxifen has been the mainstay of endocrine treatment for patients with early and advanced breast cancer for many years. Following tamoxifen treatment failure, however, there are still limited options for subsequent hormonal therapy. We discovered a novel compound, NK150460, that inhibits 17β-estradiol (E2)-dependent transcription without affecting binding of E2 to ER. Against our expectations, NK150460 inhibited growth of not only most ER-positive, but also some ER-negative breast cancer cell lines, while never inhibiting growth of non-breast cancer cell lines. Cell-based screening using a random shRNA library, identified aryl hydrocarbon receptor nuclear translocator (ARNT) as a key gene involved in NK150460's antitumor mechanism. siRNAs against not only ARNT but also its counterpart aryl hydrocarbon receptor (AhR) and their target protein, CYP1A1, dramatically abrogated NK150460's growth-inhibitory activity. This suggests that the molecular cascade of AhR/ARNT plays an essential role in NK150460's antitumor mechanism. Expression of ERα was decreased by NK150460 treatment, and this was inhibited by an AhR antagonist. Unlike two other AhR agonists now undergoing clinical developmental stage, NK150460 did not induce histone H2AX phosphorylation or p53 expression, suggesting that it did not induce a DNA damage response in treated cells. Cell lines expressing epithelial markers were more sensitive to NK150460 than mesenchymal marker-expressing cells. These data indicate that NK150460 is a novel AhR agonist with selective antitumor activity against breast cancer cell lines, and its features differ from those of the other two AhR agonists., (©2014 American Association for Cancer Research.)

This article presents an overview of our recent progress on the development of chelating materials. Carboxymethylated pentaethylenehexamine (CM-PEHA) and polyethyleneimine (CM-PEI) as chelating ligands show excellent performance for the solid-phase extraction of trace elements. Chelating resins immobilizing these ligands can be readily prepared by immobilizing PEHA and PEI on methacrylate resins and then carboxymethylating them. Chelating fiber can also be prepared with a wet spinning technique using a mixture of a viscose solution and a solution containing fine particulate CM-PEHA resin or CM-PEI. The potentials of these chelating materials for the separation and preconcentration of trace elements are outlined.

The potential of Presep(®) PolyChelate as a chelating resin was studied in detail. The chelating resin with extraction capacity for Cu of 0.30 mmol L(-1) could quantitatively extract Cd, Co, Cu, Fe, Mo, Ni, Pb, V, and Zn at pH 4 or 5.5; however, only very scant amounts of Na, K, Mg, and Ca were captured at pH levels below 7. The quantitative extraction could be achieved in 100 - 1000 mL of artificial seawater and at a flow rate of 3 - 30 mL min(-1). The performance of Presep(®) PolyChelate was compared to the other aminocarboxylic acid-type chelating resins, including Nobias Chelate-PA1, Chelex 100, Muromac B-1, Lewatit TP 207, and NTA Superflow, under the same conditions. The solid-phase extraction of the nine elements in the certified reference material (ES-L-1, ground water) and a commercially available table salt was also demonstrated.

A simple and sensitive suppressed ion chromatography (IC) method with conductivity detection for the determination of molybdate in environmental water is proposed. Molybdate in highly saline water was extracted and preconcentrated. Preconcentration was accomplished by using a chelating resin using a chelating resin immobilized with carboxymethylated polyethylenimine (Presep(®) PolyChelate). This resin is able to trap a variety of metal elements without any interference of alkali and alkaline-earth metals. A 30-mL volume of brackish water was adjusted for appropriate pH and then flushed through 100 mg of the chelating resin. Molybdate concentrated on the resin could be easily eluted with 6 mL of 0.1 M NaOH. A large volume injection method for IC was achieved with in-line neutralization of the effluent. The determination of 0.6 μg L(-1) molybdate in highly saline water was made possible with a 500-μL injection. Samples of brackish water were taken at various distances from the river mouth. The determined concentrations of molybdate correlated closely with concentrations of chloride.

The extraction of cobalt(II) from solutions containing various concentrations of lithium chloride, hydrochloric acid, and mixtures of lithium chloride plus hydrochloric acid is reported using a poly(vinyl chloride) (PVC)-based polymer inclusion membrane (PIM) containing 40% (w/w) Aliquat 336 as a carrier. The extraction from lithium chloride solutions and mixtures with hydrochloric acid is shown to be more effective than extraction from hydrochloric acid solutions alone. The solution concentrations giving the highest amounts of extraction are 7 mol L(-1) for lithium chloride and 8 mol L(-1) lithium chloride plus 1 mol L(-1) hydrochloric acid for mixed solutions. Cobalt(II) is easily stripped from the membrane using deionized water. The cobalt(II) species extracted into the membrane are CoCl(4)(2-) for lithium chloride solutions and HCoCl(4)(-) for mixed solutions; these form ion-pairs with Aliquat 336. It is also shown that both lithium chloride and hydrochloric acid are extracted by the PIM and suppress the extraction of cobalt(II) by forming ion-pairs in the membrane (i.e. R(3)MeN(+)·HCl(2)(-) for hydrochloric acid and R(3)MeN(+)·LiCl(2)(-) for lithium chloride)., (2011 © The Japan Society for Analytical Chemistry)

Solid phase extraction using a mini cartridge packed with 22 mg of chelate resin immobilizing carboxymethylated pentaethylenehexamine was successfully utilized for separation/preconcentration of cadmium in water samples prior to liquid electrode plasma atomic emission spectrometric (LEP-AES) determination. The combined method with the extraction and LEP-AES was applicable to the determination of cadmium in the certified reference materials (EU-L-1 wastewater and ES-L-1 groundwater); the detection limit was 0.20 microg in 200 mL of sample solution (500-fold preconcentration).

A useful method to separate/concentrate lanthanoids was developed based on a rapid coprecipitation technique using yttrium phosphate. Lanthanoids, which were quantitatively coprecipitated at pH 3 with yttrium phosphate, could be readily determined by inductively coupled plasma atomic emission spectrometry with indium used as an internal standard element. The detection limits ranged from 0.0003 microg (Yb, Lu) to 0.0099 microg (Er) in 100 mL of sample solutions. The proposed method was applicable to the separation/concentration of lanthanoids in NIST SRM 1515 (apple leaves).

CD28 stimulation contributes to activation of the IL-2 promoter by up-regulating the activity of several transcription factors, including nuclear factor kappaB (NF-kappaB)/Rel family members. However, the signal-transducing cascades linking the CD28 molecule and activation of NF-kappaB remain unclear. Protein kinase C (PKC) , CARMA1 and Bcl10 have recently been reported to integrate TCR-mediated NF-kappaB activation. However, since the data in these studies were drawn from experiments in which T cells were usually stimulated with both TCR and CD28, the relative contributions of TCR- and CD28-mediated signals to initiation of the NF-kappaB pathway remain elusive. To examine the role of these molecules in NF-kappaB activation through CD28-mediated stimulation, Bcl10 was over-expressed in Jurkat cells and their NF-kappaB activation by CD28- or TCR-cross-linking was evaluated. We found that CD28 stimulation alone can induce NF-kappaB activation in Bcl10-over-expressing Jurkat cells, whereas TCR stimulation alone has only little effect. In addition, we found that Bcl10-induced NF-kappaB activation through CD28-mediated stimulation could be blocked by the dominant-negative form of PKC or CARMA1. Furthermore, genetic studies revealed that Grb2/Gads binding, but not phosphatidylinositol 3-kinase binding, is important in CD28-mediated NF-kappaB activation. These findings indicate that the PKC-CARMA1-Bcl10 signaling pathway participates in the CD28 co-stimulatory signal independently of the TCR-signaling pathway, which leads us to propose that the activation of the NF-kappaB-signaling pathway via PKC-CARMA1-Bcl10 may be markedly dependent on CD28 stimulation rather than TCR stimulation.

Topoisomerase II (Top2) is a ubiquitous nuclear enzyme that relieves torsional stress in chromosomal DNA during various cellular processes. Agents that target Top2, involving etoposide, doxorubicin, and mitoxantrone, are among the most effective anticancer drugs used in the clinic. Mammalian cells possess two genetically distinct Top2 isoforms, both of which are the target of these agents. Top2alpha is essential for cell proliferation and is highly expressed in vigorously growing cells, whereas Top2beta is nonessential for growth and has recently been implicated in treatment-associated secondary malignancies, highlighting the validity of a Top2alpha-specific drug for future cancer treatment; however, no such agent has been hitherto reported. Here we show that NK314, a novel synthetic benzo[c]phenanthridine alkaloid, targets Top2alpha and not Top2beta in vivo. Unlike other Top2 inhibitors, NK314 induces Top2-DNA complexes and double-strand breaks (DSBs) in an alpha isoform-specific manner. Heterozygous disruption of the human TOP2alpha gene confers increased NK314 resistance, whereas TOP2beta homozygous knock-out cells display increased NK314 sensitivity, indicating that the alpha isoform is the cellular target. We further show that the absence of Top2beta does not alleviate NK314 hypersensitivity of cells deficient in non-homologous end-joining, a critical pathway for repairing Top2-mediated DSBs. Our results indicate that NK314 acts as a Top2alpha-specific poison in mammalian cells, with excellent potential as an efficacious and safe chemotherapeutic agent. We also suggest that a series of human knock-out cell lines are useful in assessing DNA damage and repair induced by potential topoisomerase-targeting agents.

Yttrium hydroxide quantitatively coprecipitated Be(II), Ti(IV), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II) at pH 9.6 - 10.0 for seawater and pH 10.5 - 11.4 for a table-salt solution. The coprecipitated elements could be determined by inductively coupled plasma atomic emission spectrometry; yttrium was used as an internal standard element. The detection limits ranged from 0.001(6) microg (Mn(II)) to 0.22 microg (Zn(II)) in 100 mL of sample solutions. The operation time required to separate 11 elements was approximately 30 min.

Phenol is degraded by biological treatment, however mineralization requires long time. To decrease the time and operational cost necessary for the mineralization of phenol, an optimum operation condition of the combined biological-photocatalytical treatment was investigated. The mineralization of phenol (50 mg l(-1)) was conducted in a flow-type biomembrane tank combined with a batch-type TiO2-suspended photocatalytic reactor. Phenol was degraded biologically to the concentration of 6.8 mg l(-1), an effective concentration for further photocatalytic treatment. After the biological treatment, the biotreated phenol was treated photocatalytically to complete the mineralization of phenol. The combined treatment shortened the mineralization time compared to the biological treatment and electric cost compared to the photocatalytic treatment only. The combined treatment may be suitable for a short-time mineralization of phenol in wastewater.

Fe-doped TiO2 was prepared by the calcination of Fe(x)TiS(2) (x=0, 0.002, 0.005, 0.008, 0.01) and characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and UV-visible diffuse reflectance spectra. All the Fe-doped TiO2 were composed of an anatase crystal form and showed red shifts to a longer wavelength. The activity of the Fe-doped TiO2 for the degradation of phenol was investigated by varying the iron content during UV (365nm) and visible light (405nm and 436nm) irradiation. The degradation rate depended on the Fe content and the Fe-doped TiO2 was responsive to the visible light as well as the elevated activity toward UV light. The molar ratio of 0.005 was the optimum for both the UV and visible light irradiations. The result was discussed on the basis of the balance of the excited electron-hole trap by the doped Fe(3+) and their charge recombination on the doped Fe(3+) level. The Fe-doped TiO2 (x=0.005) was more active than P25 TiO2 under solar light irradiation. The suspended Fe-doped TiO2 spontaneously precipitated once the stirring of the reaction mixture was terminated.

Within the nuclear receptor superfamily, Nur77, Nurr1, and NOR1 constitute the nuclear receptor subfamily 4 group A. Modulation of NOR1 function would be therapeutic potential for diseases related to dysfunction of NOR1, including extraskeletal myxoid chondrosarcoma and autoimmune diseases. By screening arachidonate metabolites for their capacity of transcriptional activation, we have identified prostaglandin (PG) A2 as a transactivator for NOR1. PGA2 acted as a potent activator of NOR1-dependent transcription through the GAL4-based reporter system. The putative ligand-binding domain (LBD) of the receptor directly bound PGA2, and LBD-deleted receptor showed little transcriptional activation by PGA2. Primary cultured spleen cells derived from transgenic mice overexpressing NOR1, showed higher sensitivity to PGA2 compared to those from wild-type mice. These observations suggest that PGA2 can serve as a transactivator of NOR1, and thus suggest a possibility of pharmacological modulation of the NOR1 pathways by PGA2-related compounds.

Cadmium ranging from 1 - 8 ng could be coprecipitated quantitatively with lanthanum phosphate at pH 5 - 6 from up to 200 mL of river water samples spiked with 5 microg of indium as an internal standard. Cadmium and indium coprecipitated were measured by using electrothermal atomic absorption spectrometry. The cadmium content in the original sample solution could be determined by internal standardization with indium. Since complete collection of the precipitate and strict adjustment of the volume of the final solution after coprecipitation are not required in this method, the precipitate could be collected by using decantation and centrifugation, and then dissolved with 1 mL of about 2.4 mol L(-1) nitric acid. The proposed method is simple and rapid, and enrichment close to 200-times can be attained; the detection limit (3sigma, n = 6) was 0.63 ng L(-1) in 200 mL of the sample solution.

By applying an internal standardization, we could use a rapid coprecipitation technique using lanthanum phosphate as a coprecipitant for preconcentration of iron(III) and lead in their flame atomic absorption spectrometric determination. Indium as an internal standard was added to the initial sample solution together with lanthanum and phosphoric acid; the coprecipitation of iron(III) and lead was then carried out at pH about 3. After measuring the atomic absorbances of iron, lead, and indium in the final sample solution, we determined the contents of iron(III) and lead in the original sample solution by using the internal standardization with indium. In this method, complete collection of the precipitate was not required after the coprecipitation of iron(III), lead, and indium, because the ratio of the recovery of iron(III) or lead to that of indium was almost constant regardless of the recovery of the precipitate. This method was simple and rapid, and was available for the determination of 2-300 micrograms L-1 of iron(III) and 5-400 micrograms L-1 of lead in some water samples.

Cachexic patients with chronic obstructive pulmonary disease (COPD) show abnormalities of the autonomic nervous system (ANS), neuroendocrine function, and energy expenditure. Leptin has been implicated in the regulation of ANS, neuroendocine function, and thermogenesis in humans. We assessed the physiologic significance of the circadian rhythm of circulating leptin using power spectrum analysis of heart rate variability (HRV) in nine cachexic male patients with COPD, eight noncachexic patients with COPD, and seven healthy control subjects. A diurnal pattern of 24-h leptin levels was present in both the control subjects (analysis of variance [ANOVA]; F = 7.80, p < 0.0001) and noncachexic COPD patients (F = 9.29, p < 0.0001), but was strikingly absent in the cachexic COPD patients (F = 2.09, p = NS). Analysis of HRV demonstrated that the diurnal rhythm of 24-h very low frequency (VLF; 0.003 to 0.04 Hz) showed significantly identical fluctuations with those of 24-h leptin levels, in all of the three groups (r = 0.388, p < 0.0001). Because VLF has been considered to reflect neuroendocrine and thermoregulatory influences, these data may suggest that the loss of circadian rhythm of circulating leptin has clinical importance in the pathophysiologic features in cachexic patients with COPD.

Conversion of NO2, HNO2 gas, their mixture and a mixed gas of HNO2 and HNO3 on silica particles was investigated under simulated atmospheric conditions. Both HNO2 and HNO3 were detected as the products from conversion of NO2 on silica particles. However, unlike HNO3, which increased with conversion time, HNO2 underwent an increase-decrease time course due to the increased HNO3 further transformed HNO2 into NO+ on silica particles. Considering the catalytic effect of HNO3 and HNO2 on the nitration of pyrene adsorbed on silica particles by NO2, another electrophilic nitration path, analogous to the one that we previously reported, with NONO2+ and NON2O4+ as electrophiles was suggested. The two paths together gave an appropriate explanation for the catalytic effect of HNO2, HNO3 and their mixed gas on the nitration of the adsorbed pyrene by NO2.