ABP1-TMK auxin perception for global phosphorylation and auxin canalization.

The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1-3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.

Cell surface and intracellular auxin signalling for H+ fluxes in root growth.

Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phosphoproteomics in Arabidopsis thaliana, we advance understanding of how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on rapid regulation of apoplastic pH, a causative determinant of growth. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+ influx, causing apoplast alkalinization. Simultaneous activation of these two counteracting mechanisms poises roots for rapid, fine-tuned growth modulation in navigating complex soil environments.

TMK-based cell-surface auxin signalling activates cell-wall acidification.

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.

Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

INTRODUCTION: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. METHODS: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate <60 mL/min/1.73m2 and/or proteinuria) at baseline. Breakfast-skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the eGFR from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. RESULTS: During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p=0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI 1.29‒5.26) for the breakfast-skipping group (p=0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR and baseline proteinuria. CONCLUSION: Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.

Salivary gland-type cancers: cross-organ demographics of a rare cancer.

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

Discovery of a Plant 14-3-3 Inhibitor Possessing Isoform Selectivity and In Planta Activity.

Synthetic modulators of plant 14-3-3s are promising chemical tools both for understanding the 14-3-3-related signaling pathways and controlling plant physiology. Herein, we describe a novel small-molecule inhibitor for 14-3-3 proteins of Arabidopsis thaliana. The inhibitor was identified from unexpected products in a stock solution in dimethyl sulfoxide (DMSO) of an in-house chemical library. Mass spectroscopy, mutant-based analyses, fluorescence polarization assays, and thermal shift assays revealed that the inhibitor covalently binds to an allosteric site of 14-3-3 with isoform selectivity. Moreover, infiltration of the inhibitor to Arabidopsis leaves suppressed the stomatal aperture. The inhibitor should provide new insight into the design of potent and isoform-selective 14-3-3 modulators.

Casual Serum Triglyceride Concentrations and New-Onset Chronic Kidney Disease in the General Japanese Population: The Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease Study.

INTRODUCTION: Non-fasting triglyceride (TG) concentrations are useful for predicting various diseases, but most epidemiological studies investigated the association between fasting TG concentrations and chronic kidney disease (CKD). This study aimed to examine the association between casual (fasting or non-fasting) serum TG concentrations and new-onset CKD in the general Japanese population. METHODS: We conducted a population-based, retrospective cohort study using annual health checkup data of residents of Iki City, Nagasaki Prefecture, Japan. Between 2008 and 2019, participants without CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or proteinuria) at baseline were included. Casual serum TG concentrations were classified by sex as tertile 1 (men: <0.95 mmol/L; women: <0.86 mmol/L), tertile 2 (0.95-1.49 mmol/L; 0.86-1.25 mmol/L), and tertile 3 (≥1.50 mmol/L; ≥1.26 mmol/L). The outcome was incident CKD. Multivariable-adjusted hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model. RESULTS: 4,946 participants (2,236 [45%] men and 2,710 [55%] women; 3,666 [74%] fasting and 1,182 [24%] non-fasting) were included in the present analysis. During an average follow-up of 5.2 years, 934 participants (434 men and 509 women) developed CKD. In men, the incidence rate (per 1,000 person-years) of CKD increased with an elevation in TG concentrations (tertile 1: 29.4, tertile 2: 42.2, and tertile 3: 43.3). This association was significant, even after adjustment for other risk factors of age, current smoking habits, current alcohol intake, exercise habits, obesity, hypertension, diabetes mellitus, hyper-low-density-lipoprotein cholesterolemia, and use of lipid-lowering therapy (p = 0.003 for trend). In contrast, in women, TG concentrations were not associated with incident CKD (p = 0.547 for trend). CONCLUSION: Casual serum TG concentrations are significantly associated with new-onset CKD in Japanese men in the general population.

Efficacy and Safety of Electrohydraulic Lithotripsy Using Peroral Cholangioscopy under Endoscopic Retrograde Cholangiopancreatography Guidance in Older Adults: A Single-Center Retrospective Study.

Background and objectives: The safety of electrohydraulic lithotripsy (EHL) in older adults remains unclear. We aimed to investigate the efficacy and safety of EHL using peroral cholangioscopy (POCS) under endoscopic retrograde cholangiopancreatography (ERCP) guidance in older adults aged ≥80 years. Materials and Methods: This retrospective clinical study was conducted at a single center. Fifty patients with common bile duct stones who underwent EHL using POCS under ERCP guidance at our institution, between April 2017 and September 2022, were enrolled in this study. The eligible patients were divided into an elderly group (n = 21, age ≥80 years) and a non-elderly group (n = 29, age ≤79 years), and were analyzed. Results: A total of 33 and 40 EHL procedures were performed in the elderly and non-elderly groups, respectively. After excluding cases in which stone removal was performed at other institutions, complete removal of common bile duct stones was confirmed in 93.8% and 100% of the elderly and non-elderly groups, respectively (p = 0.20). The mean number of ERCPs required for complete removal of bile duct stones was 2.9 and 4.3 in the elderly and non-elderly groups, respectively (p = 0.17). In the EHL session, the overall occurrence of adverse events was eight and seven in the elderly (24.2%) and non-elderly (17.5%) groups, respectively; however, the difference was insignificant (p = 0.48). Conclusions: EHL using POCS under ERCP guidance is effective in patients aged ≥80 years and there was no significant increase in adverse event rates compared to those aged ≤79 years.

Amyloid deposit corresponds to technetium-99m-pyrophosphate accumulation in abdominal fat of patients with transthyretin cardiac amyloidosis.

BACKGROUND: Radionuclide imaging using bone-avid tracers plays a critical role in diagnosing transthyretin cardiac amyloidosis (ATTR-CA), but technetium-99m-pyrophosphate (PYP) rarely allows the detection of extracardiac amyloid infiltration. We retrospectively investigated the frequency of PYP uptake in the subcutaneous abdominal fat of patients with ATTR-CA and its relevance to the results of fine-needle aspiration biopsy (FNAB) of this tissue. METHODS: Chest-centered images of PYP scintigraphy were obtained 2 h after the intravenous injection of the tracer (20 mCi), and the frequency of PYP uptake in the subcutaneous abdominal fat was evaluated. Amyloid deposits of fat smears taken by subcutaneous abdominal fat FNAB were assessed by Congo red staining. RESULTS: Twenty-four patients with ATTR-CA were included. Ten (41.7%) patients showed some PYP uptake in the subcutaneous abdominal fat (positive PYP group), and 14 patients did not (negative PYP group). Amyloid deposits were detected by subcutaneous abdominal fat FNAB in 7/10 patients (70.0%) of the positive PYP group versus 0/14 patients (0%) of the negative PYP group, and the difference was significant. CONCLUSIONS: In patients with ATTR-CA, abnormal PYP uptake in the subcutaneous abdominal fat could reflect the regional amyloid deposition confirmed by FNAB of this tissue.

A super-sensitive auxin-inducible degron system with an engineered auxin-TIR1 pair.

The auxin-inducible degron (AID) system enables rapid depletion of target proteins within the cell by applying the natural auxin IAA. The AID system is useful for investigating the physiological functions of essential proteins; however, this system generally requires high dose of auxin to achieve effective depletion in vertebrate cells. Here, we describe a super-sensitive AID system that incorporates the synthetic auxin derivative 5-Ad-IAA and its high-affinity-binding partner OsTIR1F74A. The super-sensitive AID system enabled more than a 1000-fold reduction of the AID inducer concentrations in chicken DT40 cells. To apply this system to various mammalian cell lines including cancer cells containing multiple sets of chromosomes, we utilized a single-step method where CRISPR/Cas9-based gene knockout is combined with insertion of a pAID plasmid. The single-step method coupled with the super-sensitive AID system enables us to easily and rapidly generate AID-based conditional knockout cells in a wide range of vertebrate cell lines. Our improved method that incorporates the super-sensitive AID system and the single-step method provides a powerful tool for elucidating the roles of essential genes.

Changes in oral function, swallowing function, and quality of life in patients with head and neck cancer: a prospective cohort study.

BACKGROUND: Head and neck cancer (HNC) treatment can cause oral morbidities, such as oral dryness and dysphagia, affecting the patient's quality of life (QOL). The relationship between oral functions and QOL in patients with early-stage HNC remains poorly studied. This study aimed to evaluate changes in the QOL of patients with early-stage HNC and identify factors that affect the QOL of these patients. METHODS: In this prospective cohort study, 37 patients who underwent early-stage (Stage I/Stage II) HNC treatment were evaluated for their oral function, swallowing function, and the QOL score at baseline (BL) and 12 months after surgical treatment (12 M). The participants were divided into two groups: patients who returned to the BL QOL score at 12 M (RE; n = 26) and those who did not (NR; n = 11). RESULTS: In total, 29.7% (11/37) patients with early-stage HNC did not return to the BL QOL score at 12 M. There was no significant difference between the RE and NR groups regarding the oral and swallowing function. Moreover, oral and swallowing function of all patients returned to the BL at 12 M. The NR group showed lower QOL scores than the RE group in the global health status, and "sticky saliva" parameters in the questionnaires. CONCLUSION: Restoration of the oral function is insufficient to improve the QOL of patients with early-stage HNC. The treatment of these patients should instead consider several factors that affect their QOL.

Transnasal transplantation of human induced pluripotent stem cell-derived microglia to the brain of immunocompetent mice.

Microglia are the resident immune cells of the brain, and play essential roles in neuronal development, homeostatic function, and neurodegenerative disease. Human microglia are relatively different from mouse microglia. However, most research on human microglia is performed in vitro, which does not accurately represent microglia characteristics under in vivo conditions. To elucidate the in vivo characteristics of human microglia, methods have been developed to generate and transplant induced pluripotent or embryonic stem cell-derived human microglia into neonatal or adult mouse brains. However, its widespread use remains limited by the technical difficulties of generating human microglia, as well as the need to use immune-deficient mice and conduct invasive surgeries. To address these issues, we developed a simplified method to generate induced pluripotent stem cell-derived human microglia and transplant them into the brain via a transnasal route in immunocompetent mice, in combination with a colony stimulating factor 1 receptor antagonist. We found that human microglia were able to migrate through the cribriform plate to different regions of the brain, proliferate, and become the dominant microglia in a region-specific manner by occupying the vacant niche when exogenous human cytokine is administered, for at least 60 days.

Identification of three closely linked loci conferring broad-spectrum Phytophthora sojae resistance in soybean variety Tosan-231.

KEY MESSAGE: A variable genomic region containing two Harosoy-derived loci related to Rps7 and one Nemashirazu-derived locus confers broad-spectrum Phytophthora sojae resistance in Tosan-231 and is useful for developing resistant cultivars. We investigated resistance to pathotypically variable Phytophthora sojae isolates in the soybean variety Tosan-231, which has broad-spectrum resistance. Mapping analysis using descendent lines from a cross between Shuurei and Tosan-231 demonstrated that a genomic region between SSR markers BARCSOYSSR_03_0209 and BARCSOYSSR_03_0385 (termed "Region T"), confers broad-spectrum resistance in Tosan-231 and contains three closely linked resistance loci. Inoculation tests with 20 P. sojae isolates of different pathotypes and simple sequence repeat (SSR) analysis of progenitors of Tosan-231 facilitated identification and characterization of Rps genes at the three resistance loci. Two resistance genes, RpsT1 and RpsT2, were found to be derived from Harosoy carrying Rps7. This result suggested two mutually exclusive possibilities: (1) either RpsT1 or RpsT2 is Rps7, and the other is a locally functional novel gene; (2) Rps7 is not a single gene but in fact comprises RpsT1 and RpsT2. The resistance locus containing RpsT3 is derived from Nemashirazu, in which Rps genes have remained poorly defined. Moreover, we identified two genomic regions with relatively high recombination frequencies on the basis of mapping information and proposed a strategy to readily assemble useful resistance genes in or around Region T.

Mechanistic Insights into Nanobubble Merging Studied Using In Situ Liquid-Phase Electron Microscopy.

Nanobubbles have attracted great interest in recent times because of their application in water treatment, surface cleaning, and targeted drug delivery, yet the challenge remains to gain thorough understanding of their unique behavior and dynamics for their utilization in numerous potential applications. In this work, we have used a liquid-phase electron microscopy technique to gain insights into the quasistatic merging of surface nanobubbles. The electron beam environment was controlled in order to suppress any new nucleation and slow down the merging process. The transmission electron microscopy study reveals that merging of closely positioned surface nanobubbles is initiated by gradual localized changes in the physical properties of the region between the adjoining nanobubble boundary. The observed phenomenon is then analyzed and discussed based on the different perceptions: localized liquid density gradient and bridge formation for gas exchange. In this study, it is estimated that the merging of the stable nanobubbles is initiated by the formation of a thin gas layer. This work not only enhances our understanding of the merging process of stable surface nanobubbles but will also lead to exploration of new domains for nanobubble applications.

Reflected Laser Interferometry: A Versatile Tool to Probe Condensation of Low-Surface-Tension Droplets.

Experimental investigation of dropwise condensation of low-surface-tension liquids remains prone to error owing to the imaging difficulties caused by the typically low droplet height. Using reflection interference contrast microscopy in confocal mode, we demonstrate a noninvasive framework to accurately capture this condensation dynamics of volatile liquids with low surface tension. The capability of the developed framework is demonstrated in studying the condensation dynamics of acetone, where it accurately describes the growth mechanism of condensed microdroplets with excellent spatiotemporal resolution even for submicron-range drop height and a three-phase contact angle of <5°. From experimentally obtained interferograms, the framework can reconstruct three-dimensional topography of the microdroplets even when the contact line of the droplet is distorted due to strong local pinning. The obtained results exhibit excellent quantitative agreement with several theoretically predicted trends. The proposed protocol overcomes the limitation of conventional techniques (e.g., optical imaging/environmental scanning electron microscopy) and provides an efficient alternative for studying the condensation of low-surface-tension liquids under atmospheric conditions.

Pinning in a Contact and Noncontact Manner: Direct Observation of a Three-Phase Contact Line Using Graphene Liquid Cells.

Pinning of a three-phase contact line at the nanoscale cannot be explained by conventional macroscale theories and thus requires an experimental insight to understand this phenomenon. We performed in-situ transmission electron microscopy observation of the three-phase contact lines of bubbles inside graphene liquid cells to experimentally investigate the causes of nanoscale pinning. In our observations, the three-phase contact line was not affected by the 0.6 nm-thick inhomogeneity of the graphene surface, but thicker metal nanoparticles with diameters of 2-10 nm and nanoflakes caused pinning of the gas-liquid interface. Notably, we found that flake-like objects can cause pinning that prevents the bubble overcome the flake object in a noncontact state, with a 2 nm-thick liquid film between them and the bubble. This phenomenon can be explained by the repulsive force obtained using the Derjaguin, Landau, Verwey, and Overbeek theory. We also observed that the flake temporally prevented the gas-liquid interface moving away from the flake. We discussed the physical mechanism of the attractive force-like phenomenon by considering the nanoconfinement effect of the liquid sandwiched by two graphene sheets and the hydration layer formed near the solid surface.

Dynamic interplay between interfacial nanobubbles: oversaturation promotes anisotropic depinning and bubble coalescence.

Probing the dynamics of nanobubbles is essential to understand their longevity and behavior. Importantly, such an observation requires tools and techniques having high temporal resolutions to capture the intrinsic characteristics of the nanobubbles. In this work, we have used the in situ liquid-phase electron microscopy (LPEM) technique to gain insights into nanobubbles' behavior and their interfacial dynamics. Interestingly, we could observe a freely growing-shrinking nanobubble and a pinned nanobubble under the same experimental conditions, suggesting the possibility of multiple nanobubble stabilization theories and pathways. Remarkably, the study reveals that a freely growing-shrinking nanobubble induces anisotropic depinning in the three-phase contact line of a strongly pinned neighboring nanobubble. The anisotropic depinning is attributed to the differential local gas saturation levels, depending on the relative positioning of the freely growing-shrinking nanobubble. Furthermore, we also observed a unique pull-push phenomenon exhibited by the nanobubble's interfaces, which is attributed to the van der Waals interactions and the electric double layer collectively. The role of the electric double layer in suppressing and delaying the merging is also highlighted in this study. The present work aims to reveal the role of locally varying gas saturation in the depinning of nanobubbles, their longevity due to the electric double layer, and the consequent coalescence, which is crucial to understand the behavior of the nanobubbles. Our findings will essentially contribute to the understanding of these novel nanoscale gaseous domains and their dynamics.

Current status of medical oncology in Japan and changes over the most recent 7-year period: results of a questionnaire sent to designated cancer care hospitals.

BACKGROUND: According to a questionnaire sent to Designated Cancer Care Hospitals in Japan in 2013, only 39.4% of the institutes had medical oncology departments. Furthermore, most of these medical oncology departments were primarily responsible for the treatment of limited disease categories and the administration of newly developed therapeutic modalities, including molecular-targeted therapy. The aim of the present study was to update these previous findings and to clarify the changes over the intervening 7-year period. METHODS: The questionnaire was sent to all 393 Designated Cancer Care Hospitals on 13 March 2020. Similar to the previous questionnaires, questions were asked regarding the presence of a medical oncology department, the number of physicians in the department and the degrees of responsibility for drug therapies provided by medical oncologists to adult patients with solid cancers. RESULTS: In total, 270 institutions (68.7%) responded. Overall, 145 of these 270 institutions (53.7%) had medical oncology departments, representing a significant increase compared with the results of the previous study (P < 0.01). Among the institutions with a medical oncology department, these departments were responsible for the administration of over 30% of all cytotoxic and molecular-targeted drug therapies for extragonadal germ cell tumors, cancers of unknown primary site, soft tissues, head and neck, esophagus, stomach, colon and rectum, and pancreas as well as the administration of immune checkpoint inhibitors (ICI) for microsatellite instability-high tumors, cancers of the stomach, esophagus and head and neck, and melanoma. CONCLUSION: The proportion of institutes with medical oncology departments in Japan has increased. In addition, the responsibility of medical oncology departments has expanded to include newly emerging drugs, such as ICIs.

Suppression of amiodarone-induced torsade de pointes by landiolol in a patient with atrial fibrillation-mediated cardiomyopathy.

An elderly Japanese woman developed acute decompensated heart failure caused by persistent atrial fibrillation (AF) and left ventricular systolic dysfunction. Approximately 6 days after starting intravenous administration of amiodarone (600 mg/day) for maintaining sinus rhythm after cardioversion of AF, electrocardiograms revealed a prolonged QT interval associated with torsade de pointes (TdP). The amiodarone-induced TdP disappeared after intravenous administration of landiolol plus magnesium and potassium, without discontinuation of amiodarone or overdrive cardiac pacing, although the prolonged QT interval persisted. To the best of our knowledge, this is the first report that landiolol could be effective for amiodarone-induced TdP.

Association between serum uric acid and new onset and progression of chronic kidney disease in a Japanese general population: Iki epidemiological study of atherosclerosis and chronic kidney disease.

BACKGROUND: Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. METHODS: This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. RESULTS: During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03-1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92-1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. CONCLUSION: SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.