Association between Fiber Intake and Risk of Incident Chronic Kidney Disease: The UK Biobank Study.

OBJECTIVES: Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the development of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes. RESULTS: A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for incident CKD were 0.85 (0.77-0.94), 0.78 (0.70-0.86), and 0.76 (0.68-0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +∆1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95-0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation. CONCLUSION: Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.

In-plane uniaxial pressure-induced out-of-plane antiferromagnetic moment and critical fluctuations in BaFe2As2.

A small in-plane external uniaxial pressure has been widely used as an effective method to acquire single domain iron pnictide BaFe2As2, which exhibits twin-domains without uniaxial strain below the tetragonal-to-orthorhombic structural (nematic) transition temperature Ts. Although it is generally assumed that such a pressure will not affect the intrinsic electronic/magnetic properties of the system, it is known to enhance the antiferromagnetic (AF) ordering temperature TN ( < Ts) and create in-plane resistivity anisotropy above Ts. Here we use neutron polarization analysis to show that such a strain on BaFe2As2 also induces a static or quasi-static out-of-plane (c-axis) AF order and its associated critical spin fluctuations near TN/Ts. Therefore, uniaxial pressure necessary to detwin single crystals of BaFe2As2 actually rotates the easy axis of the collinear AF order near TN/Ts, and such effects due to spin-orbit coupling must be taken into account to unveil the intrinsic electronic/magnetic properties of the system.

Anisotropic spin fluctuations in detwinned FeSe.

Superconductivity in FeSe emerges from a nematic phase that breaks four-fold rotational symmetry in the iron plane. This phase may arise from orbital ordering, spin fluctuations or hidden magnetic quadrupolar order. Here we use inelastic neutron scattering on a mosaic of single crystals of FeSe, detwinned by mounting on a BaFe2As2 substrate to demonstrate that spin excitations are most intense at the antiferromagnetic wave vectors QAF = (±1, 0) at low energies E = 6-11 meV in the normal state. This two-fold (C2) anisotropy is reduced at lower energies, 3-5 meV, indicating a gapped four-fold (C4) mode. In the superconducting state, however, the strong nematic anisotropy is again reflected in the spin resonance (E = 3.6 meV) at QAF with incommensurate scattering around 5-6 meV. Our results highlight the extreme electronic anisotropy of the nematic phase of FeSe and are consistent with a highly anisotropic superconducting gap driven by spin fluctuations.

Microscopic hematuria is a risk factor of incident chronic kidney disease in the Korean general population: a community-based prospective cohort study.

BACKGROUND: Although asymptomatic microscopic hematuria (MH) is a common finding in clinical practice, its long-term outcome remains unknown. AIM: This study evaluated the clinical implication of MH in the general population using a large-scale long-term longitudinal cohort database. METHODS: This study included 8719 participants from the Korean Genome and Epidemiology Study between 2001 and 2014. MH was defined as ≥5 red blood cells per high-power field in random urinalysis without evidence of pyuria. The primary study outcome measure was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate <60 ml min-1⋅1.73⋅m-2. RESULTS: During a median follow-up of 11.7 years, CKD occurred in 677 (7.8%) subjects. In Cox regression after adjustment for multiple confounders, subjects with MH had a significantly higher risk of incident CKD than those without [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.12-1.87; P = 0.005]. Isolated MH without proteinuria was also a risk factor of incident CKD (HR 1.37, 95% CI 1.04-1.79; P = 0.023) and the risk was further increased in MH with concomitant proteinuria (HR 5.41, 95% CI 2.54-11.49; P < 0.001). In propensity score matching analysis after excluding subjects with proteinuria, multi-variable stratified Cox regression analysis revealed that subjects with isolated MH had a significantly higher risk of incident CKD than those without (HR 1.83, 95% CI 1.14-2.94; P = 0.012). CONCLUSION: The presence of MH is associated with an increased risk of incident CKD in the general population. Therefore, attentive follow-up is warranted in persons with MH for early detection of CKD.

Structure of spin excitations in heavily electron-doped Li0.8Fe0.2ODFeSe superconductors.

Heavily electron-doped iron-selenide high-transition-temperature (high-T c) superconductors, which have no hole Fermi pockets, but have a notably high T c, have challenged the prevailing s ± pairing scenario originally proposed for iron pnictides containing both electron and hole pockets. The microscopic mechanism underlying the enhanced superconductivity in heavily electron-doped iron-selenide remains unclear. Here, we used neutron scattering to study the spin excitations of the heavily electron-doped iron-selenide material Li0.8Fe0.2ODFeSe (T c = 41 K). Our data revealed nearly ring-shaped magnetic resonant excitations surrounding (π, π) at ∼21 meV. As the energy increased, the spin excitations assumed a diamond shape, and they dispersed outward until the energy reached ∼60 meV and then inward at higher energies. The observed energy-dependent momentum structure and twisted dispersion of spin excitations near (π, π) are analogous to those of hole-doped cuprates in several aspects, thus implying that such spin excitations are essential for the remarkably high T c in these materials.The microscopic mechanism underlying an enhanced superconductivity in electron-doped iron selenide superconductor remains unclear. Here, Pan et al. report the spin excitations of Li0.8Fe0.2ODFeSe, revealing analogous momentum structure and dispersion to hole-doped cuprates.

Spin-Wave Excitations Evidencing the Kitaev Interaction in Single Crystalline α-RuCl_{3}.

Kitaev interactions underlying a quantum spin liquid have long been sought, but experimental data from which their strengths can be determined directly, are still lacking. Here, by carrying out inelastic neutron scattering measurements on high-quality single crystals of α-RuCl_{3}, we observe spin-wave spectra with a gap of ∼2 meV around the M point of the two-dimensional Brillouin zone. We derive an effective-spin model in the strong-coupling limit based on energy bands obtained from first-principles calculations, and find that the anisotropic Kitaev interaction K term and the isotropic antiferromagnetic off-diagonal exchange interaction Γ term are significantly larger than the Heisenberg exchange coupling J term. Our experimental data can be well fit using an effective-spin model with K=-6.8 meV and Γ=9.5 meV. These results demonstrate explicitly that Kitaev physics is realized in real materials.

Effect of Nematic Order on the Low-Energy Spin Fluctuations in Detwinned BaFe_{1.935}Ni_{0.065}As_{2}.

The origin of nematic order remains one of the major debates in iron-based superconductors. In theories based on spin nematicity, one major prediction is that the spin-spin correlation length at (0,π) should decrease with decreasing temperature below the structural transition temperature T_{s}. Here, we report inelastic neutron scattering studies on the low-energy spin fluctuations in BaFe_{1.935}Ni_{0.065}As_{2} under uniaxial pressure. Both intensity and spin-spin correlation start to show anisotropic behavior at high temperature, while the reduction of the spin-spin correlation length at (0,π) happens just below T_{s}, suggesting the strong effect of nematic order on low-energy spin fluctuations. Our results favor the idea that treats the spin degree of freedom as the driving force of the electronic nematic order.

Transition from Sign-Reversed to Sign-Preserved Cooper-Pairing Symmetry in Sulfur-Doped Iron Selenide Superconductors.

An essential step toward elucidating the mechanism of superconductivity is to determine the sign or phase of the superconducting order parameter, as it is closely related to the pairing interaction. In conventional superconductors, the electron-phonon interaction induces attraction between electrons near the Fermi energy and results in a sign-preserved s-wave pairing. For high-temperature superconductors, including cuprates and iron-based superconductors, prevalent weak coupling theories suggest that the electron pairing is mediated by spin fluctuations which lead to repulsive interactions, and therefore that a sign-reversed pairing with an s_{±} or d-wave symmetry is favored. Here, by using magnetic neutron scattering, a phase sensitive probe of the superconducting gap, we report the observation of a transition from the sign-reversed to sign-preserved Cooper-pairing symmetry with insignificant changes in T_{c} in the S-doped iron selenide superconductors K_{x}Fe_{2-y}(Se_{1-z}S_{z})_{2}. We show that a rather sharp magnetic resonant mode well below the superconducting gap (2Δ) in the undoped sample (z=0) is replaced by a broad hump structure above 2Δ under 50% S doping. These results cannot be readily explained by simple spin fluctuation-exchange pairing theories and, therefore, multiple pairing channels are required to describe superconductivity in this system. Our findings may also yield a simple explanation for the sometimes contradictory data on the sign of the superconducting order parameter in iron-based materials.

Commensurate antiferromagnetic excitations as a signature of the pseudogap in the tetragonal high-Tc cuprate HgBa2CuO(4+δ).

Antiferromagnetic correlations have been argued to be the cause of the d-wave superconductivity and the pseudogap phenomena exhibited by the cuprates. Although the antiferromagnetic response in the pseudogap state has been reported for a number of compounds, there exists no information for structurally simple HgBa2CuO(4+δ). Here we report neutron-scattering results for HgBa2CuO(4+δ) (superconducting transition temperature Tc≈71 K, pseudogap temperature T*≈305 K) that demonstrate the absence of the two most prominent features of the magnetic excitation spectrum of the cuprates: the X-shaped 'hourglass' response and the resonance mode in the superconducting state. Instead, the response is Y-shaped, gapped and significantly enhanced below T*, and hence a prominent signature of the pseudogap state.

Suppression of spin-exciton state in hole overdoped iron-based superconductors.

The mechanism of Cooper pair formation in iron-based superconductors remains a controversial topic. The main question is whether spin or orbital fluctuations are responsible for the pairing mechanism. To solve this problem, a crucial clue can be obtained by examining the remarkable enhancement of magnetic neutron scattering signals appearing in a superconducting phase. The enhancement is called spin resonance for a spin fluctuation model, in which their energy is restricted below twice the superconducting gap value (2Δs), whereas larger energies are possible in other models such as an orbital fluctuation model. Here we report the doping dependence of low-energy magnetic excitation spectra in Ba1-xKxFe2As2 for 0.5 < x < 0.84 studied by inelastic neutron scattering. We find that the behavior of the spin resonance dramatically changes from optimum to overdoped regions. Strong resonance peaks are observed clearly below 2Δs in the optimum doping region, while they are absent in the overdoped region. Instead, there is a transfer of spectral weight from energies below 2Δs to higher energies, peaking at values of 3Δs for x = 0.84. These results suggest a reduced impact of magnetism on Cooper pair formation in the overdoped region.

Magnon spectrum of the helimagnetic insulator Cu2OSeO3.

Complex low-temperature-ordered states in chiral magnets are typically governed by a competition between multiple magnetic interactions. The chiral-lattice multiferroic Cu2OSeO3 became the first insulating helimagnetic material in which a long-range order of topologically stable spin vortices known as skyrmions was established. Here we employ state-of-the-art inelastic neutron scattering to comprehend the full three-dimensional spin-excitation spectrum of Cu2OSeO3 over a broad range of energies. Distinct types of high- and low-energy dispersive magnon modes separated by an extensive energy gap are observed in excellent agreement with the previously suggested microscopic theory based on a model of entangled Cu4 tetrahedra. The comparison of our neutron spectroscopy data with model spin-dynamical calculations based on these theoretical proposals enables an accurate quantitative verification of the fundamental magnetic interactions in Cu2OSeO3 that are essential for understanding its abundant low-temperature magnetically ordered phases.

A novel cis-AB variant allele arising from a de novo nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene.

BACKGROUND: Cis-AB, a rare ABO variant, is the result of a mutated ABO gene that produces a glycosyltransferase enzyme with dual A and B glycosyltransferase activity. It may lead to ABO discrepancies and a delay in establishing the blood group. To date, there have been no reports of a de novo mutation leading to a cis-AB allele. OBJECTIVES AND METHODS: Sequencing of the ABO gene using blood and hair follicle cells from the proposita were performed along with blood from her parents. To establish maternity and paternity, short tandem repeat (STR) analysis was also performed. The A and B enzyme activities of the novel enzyme were measured in an in vitro expression study. RESULTS: A novel cis-AB allele arising from nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene were discovered in the blood and hair follicle cells from the proposita, which was absent from her parents. In all 15 autosomal STR loci analysed, the probability of maternity and paternity were 0.999999 and 0.999989, respectively. The novel enzyme created 33.1% and 60.2% of A and B antigen compared to wild type A and B glycosyltransferases. CONCLUSION: A novel mechanism leading to a cis-AB allele was discovered.

Differential in vivo tumorigenicity of diverse KRAS mutations in vertebrate pancreas: A comprehensive survey.

Somatic activation of the KRAS proto-oncogene is evident in almost all pancreatic cancers, and appears to represent an initiating event. These mutations occur primarily at codon 12 and less frequently at codons 13 and 61. Although some studies have suggested that different KRAS mutations may have variable oncogenic properties, to date there has been no comprehensive functional comparison of multiple KRAS mutations in an in vivo vertebrate tumorigenesis system. We generated a Gal4/UAS-based zebrafish model of pancreatic tumorigenesis in which the pancreatic expression of UAS-regulated oncogenes is driven by a ptf1a:Gal4-VP16 driver line. This system allowed us to rapidly compare the ability of 12 different KRAS mutations (G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D, Q61L, Q61R and A146T) to drive pancreatic tumorigenesis in vivo. Among fish injected with one of five KRAS mutations reported in other tumor types but not in human pancreatic cancer, 2/79 (2.5%) developed pancreatic tumors, with both tumors arising in fish injected with A146T. In contrast, among fish injected with one of seven KRAS mutations known to occur in human pancreatic cancer, 22/106 (20.8%) developed pancreatic cancer. All eight tumorigenic KRAS mutations were associated with downstream MAPK/ERK pathway activation in preneoplastic pancreatic epithelium, whereas nontumorigenic mutations were not. These results suggest that the spectrum of KRAS mutations observed in human pancreatic cancer reflects selection based on variable tumorigenic capacities, including the ability to activate MAPK/ERK signaling.

Childhood facial vitiligo: how intractable is it?

BACKGROUND: Following the recent elucidation of its pathogenic mechanisms involving reactive oxygen species, use of vitamins, folic acid and antioxidants as adjuvant therapy has been suggested. OBJECTIVE: To evaluate the long-term outcome of childhood facial vitiligo who were treated with nutritional education, vitamin E (α-tocopherol 100-400 IU/day), folic acid (1-2 mg/day) and multivitamin intake and antioxidant cosmetics as the mainstay of treatment as well as the conventional therapies including oral, topical and/or intralesional corticosteroid, topical macrolactam, Excimer laser and epidermal graft. METHODS: Medical data and photographs of 111 paediatric facial vitiligo patients who had been followed up for longer than 1 year from March 1, 2003 to June 30, 2013 were extracted from data warehouse of electric medical records. Photographic evaluation and final visual outcome assessment was performed. RESULT: By investigator's assessment, 9% of patients demonstrated no improvement regardless of treatment modality, whereas 91% showed improvement of lesions. Among the latter, 33.3% resulted in >75% improvement; 18% in 50%-75% improvement; 26.1% in 25%-50% improvement; and 13.5% in <25% improvement. In the final visual outcome assessment, 'Looking excellent' was seen in 42.3%; 'looking very good' in 30.6%; 'looking good' in 17.1%; 'looking fair' in 9.0%; and 'looking bad' in 0.9%. CONCLUSION: Although childhood facial vitiligo is quite refractory to treatment, the long-term outcome of this condition is not dismal with conventional vitiligo therapy along with basic nutritional therapeutic regimen.

Competing exchange interactions on the verge of a metal-insulator transition in the two-dimensional spiral magnet Sr3Fe2O7.

We report a neutron scattering study of the magnetic order and dynamics of the bilayer perovskite Sr(3)Fe(2)O(7), which exhibits a temperature-driven metal-insulator transition at 340 K. We show that the Fe(4+) moments adopt incommensurate spiral order below T(N) = 115 K and provide a comprehensive description of the corresponding spin-wave excitations. The observed magnetic order and excitation spectra can be well understood in terms of an effective spin Hamiltonian with interactions ranging up to third-nearest-neighbor pairs. The results indicate that the helical magnetism in Sr(3)Fe(2)O(7) results from competition between ferromagnetic double-exchange and antiferromagnetic superexchange interactions whose strengths become comparable near the metal-insulator transition. They thus confirm a decades-old theoretical prediction and provide a firm experimental basis for models of magnetic correlations in strongly correlated metals.

Superconductivity. Nematic spin correlations in the tetragonal state of uniaxial-strained BaFe(2-x)Ni(x)As2.

Understanding the microscopic origins of electronic phases in high-transition temperature (high-T(c)) superconductors is important for elucidating the mechanism of superconductivity. In the paramagnetic tetragonal phase of BaFe(2-x)T(x)As2 (where T is Co or Ni) iron pnictides, an in-plane resistivity anisotropy has been observed. Here, we use inelastic neutron scattering to show that low-energy spin excitations in these materials change from fourfold symmetric to twofold symmetric at temperatures corresponding to the onset of the in-plane resistivity anisotropy. Because resistivity and spin excitation anisotropies both vanish near optimal superconductivity, we conclude that they are likely intimately connected.

Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes.

AIMS/HYPOTHESIS: Translationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes-induced podocyte hypertrophy. METHODS: We investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro. RESULTS: Glomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs. CONCLUSIONS/INTERPRETATION: These findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest.

Magnetic resonant mode in the low-energy spin-excitation spectrum of superconducting Rb2Fe4Se5 single crystals.

We have studied the low-energy spin-excitation spectrum of the single-crystalline Rb(2)Fe(4)Se(5) superconductor (T(c)=32 K) by means of inelastic neutron scattering. In the superconducting state, we observe a magnetic resonant mode centered at an energy of ℏω(res)=14 meV and at the (0.5 0.25 0.5) wave vector (unfolded Fe-sublattice notation), which differs from the ones characterizing magnetic resonant modes in other iron-based superconductors. Our finding suggests that the 245-iron selenides are unconventional superconductors with a sign-changing order parameter, in which bulk superconductivity coexists with the √5×√5 magnetic superstructure. The estimated ratios of ℏω(res)/k(B)T(c)≈5.1±0.4 and ℏω(res)/2Δ≈0.7±0.1, where Δ is the superconducting gap, indicate moderate pairing strength in this compound, similar to that in optimally doped 1111 and 122 pnictides.

Reduced pre-pregnancy proteinuria is associated with improving postnatal maternal renal outcomes in IgA nephropathy women.

AIMS: In patients with immunoglobulin A (IgA) nephropathy, postnatal renal outcomes vary depending on kidney function and proteinuria. However, whether a decrease in proteinuria prior to conception improves postnatal maternal renal outcomes is unknown. METHODS: This was a single-center retrospective study. A total of 52 pregnant women with biopsy-proven IgA nephropathy were enrolled in the study between January 2004 and December 2009. We collected data on proteinuria, which had been measured 1 year prior to conception, at conception, during pregnancy, and postnatally. The study outcomes included changes in estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: The median serum creatinine, eGFR, and proteinuria levels at conception were 0.8 (0.5 - 2.6) mg/dl, 91.2 (24.1 - 157.0) ml/min, 0.7 (0.0 - 3.5) g/g, respectively. Compared with values measured at conception, serum creatinine (0.8 - 1.0 mg/dl, p < 0.01) and proteinuria (0.7 - 1.5 g/g, p < 0.01) increased significantly postnatally, while eGFR decreased (91.2 - 77.8 ml/min, p < 0.01). In a multiple linear regression analysis, proteinuria at conception were independently associated with a faster decline in postnatal maternal eGFR (ß = 4.50, p < 0.05). In addition, a less decline in maternal eGFR was observed in patients with a reduction in proteinuria (> 30%) prior to pregnancy, compared with those with a less reduction (≤ 30%). As for newborn outcomes, preterm delivery, caesarean section, low birth weight < 2,500 g, and need for neonatal intensive care were 15.4%, 46.2%, 25.0% and 7.7%, respectively. CONCLUSIONS: This study showed that in women with IgA nephropathy, proteinuria was significantly associated with the deterioration of postnatal maternal renal outcomes. Our study also suggests that a strategy for reducing proteinuria prior to pregnancy is required to preserve kidney function after delivery.

New anatomical insight of the levator labii superioris alaeque nasi and the transverse part of the nasalis.

PURPOSE: The aim of this study was to clarify the morphology and topography of the deep layer of levator labii superioris alaeque nasi muscle (LLSAN) and the transverse part of the nasalis. Anatomical variations in the topographic relationships were also described to understand the function of the LLSAN and the transverse part of the nasalis. METHODS: Anatomical dissections were performed on 40 specimens of embalmed Korean adult cadavers. RESULTS: The LLSAN was divided into two layers, which were superficial and deep in the levator labii superioris muscle (LLS), respectively. The superficial layer of LLSAN descended on the LLS, and the deep layer was located deep in the LLS. The deep layer of LLSAN originated from the superficial layer of LLSAN and the frontal process of the maxilla. It inserted between the levator anguli oris and the orbicularis oris muscles. This transverse part of the nasalis received some muscle fibers from the superficial layer of LLSAN in 90% (36/40) of specimens. The transverse part of the nasalis originated from the maxilla and ascended, passing posterior to the superficial layer of LLSAN in 65% (26/40) of specimens. However, it originated as two muscle bellies from the maxilla and the upper half of the alar facial crease, respectively, in 35% (14/40) of specimens. CONCLUSIONS: These findings will be crucial data to understand the structure and function of the LLSAN and the transverse part of the nasalis.