In 2013, we published a set of clinical practice recommendations for the treatment of Alport syndrome in this journal. We recommended delaying the initiation of angiotensin-converting enzyme ...inhibition until the onset of overt proteinuria or, in some cases, microalbuminuria. Developments that have occurred over the past 7 years have prompted us to revise these recommendations. We now recommend the initiation of treatment at the time of diagnosis in males with X-linked Alport syndrome and in males and females with autosomal recessive Alport syndrome. We further recommend starting treatment at the onset of microalbuminuria in females with X-linked Alport syndrome and in males and females with autosomal dominant Alport syndrome. This article presents the rationale for these revisions as well as recommendations for diagnostic tactics intended to ensure the early diagnosis of Alport syndrome.
Reaction of the uranium(
iii
) metallocenium salt (Cp
iPr4
)
2
UB(C
6
F
5
)
4
with
tert
-butyl isocyanide (
t
BuNC) yielded the dicationic uranium(
iv
) complex (Cp
iPr4
)
2
U(CN
t
Bu)
4
B(C
6
F
5
)
...4
2
(
1
), which displays a linear metallocene geometry. Use of crude mixtures of (Cp
iPr4
)
2
UB(C
6
F
5
)
4
, which contain a soluble source of iodide, led instead to isolation of the monocationic uranium(
iv
) iodide complex (Cp
iPr4
)
2
U(I)(CN
t
Bu)
2
B(C
6
F
5
)
4
(
2
). Adduct formation with no change in oxidation state was observed upon addition of
t
BuNC to the neutral uranium(
iii
) species (Cp
iPr4
)
2
UI, resulting in isolation of (Cp
iPr4
)
2
U(I)(CN
t
Bu) (
3
). X-ray crystallographic and IR spectroscopic studies both showed effects ascribed to the presence of multiple strongly donating isocyanide ligands in
1
.
Reactions of uranium(
iii
) metallocenium salt (Cp
iPr4
)
2
UB(C
6
F
5
)
4
with
tert
-butyl isocyanide yielded cationic uranium(
iv
) products, including a rare example of a linear f-block metallocene complex.
High energy resolution fluorescence detected XANES (HERFD-XANES) and valence-to-core X-ray emission spectroscopy (VtC-XES) are introduced as powerful tools to investigate hydride–iron interaction, ...the possible iron–iron bond, and iron spin state of the dinuclear tetra-hydrido complex {5CpFe}2(μ-H)4 (1H, 5Cp = η5-C5 iPr5) by thoroughly accessing the geometric and electronic structure of this complex in comparison to the nonhydride reference 5CpCpFe (1, Cp = C5H5). The so far observed most intense hydride induced signals in the pre-edge feature of the HERFD-XANES and in the VtC-XES spectra at the iron K-edge allow a precise analysis of the LUMO and HOMO states, respectively, by application of time-dependent density function theory (TD-DFT) and density functional theory (DFT) calculations. The results of these calculations are further employed to understand the oxidation state, spin states, and potential Fe–Fe bonds in this complex.
This open access book covers the main topics for a course on the differential geometry of curves and surfaces. Unlike the common approach in existing textbooks, there is a strong focus on variational ...problems, ranging from elastic curves to surfaces that minimize area, or the Willmore functional. Moreover, emphasis is given on topics that are useful for applications in science and computer graphics. Most often these applications are concerned with finding the shape of a curve or a surface that minimizes physically meaningful energy. Manifolds are not introduced as such, but the presented approach provides preparation and motivation for a follow-up course on manifolds, and topics like the Gauss-Bonnet theorem for compact surfaces are covered.
Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian ...glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy. Herein we propose a new classification of genetic disorders of the collagen IV α345 molecule with the goal of improving renal outcomes through regular monitoring and early treatment.
Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the ...nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.
Two new complexes, (C5Me5)FeBr(tmeda) (tmeda = tetramethylethylenediamine) and {C5(CHMe2)5}FeN(SiMe3)2, have been synthesized and characterized as high‐spin iron(II) complexes with typical distances ...between the iron atom and the center of gravity of the C5 ring (Fe–Cpcent) exceeding 190 pm and displaying paramagnetic behavior in solution. Both are analogues of known complexes, namely, the Jonas complex (C5Me5)FeCl(tmeda) and the Siemeling “pogo‐stick” complex (C5Me5)FeN(SiMe3)2. The silylamide {C5(CHMe2)5}FeN(SiMe3)2 was treated with water to yield the bridged hydroxo dimer {C5(CHMe2)5}Fe(µ‐OH)2 with high‐spin iron(II) configuration. With 2,5‐dimethylpyrrole the azaferrocene derivative {C5(CHMe2)5}Fe(NC4H2Me2‐2,5) was obtained, and with diphenylphosphine a few crystals of the diphosphine hydride {C5(CHMe2)5}FeH(HPPh2)2 as well as a sample of its dehydrogenative P–P coupling product {C5(CHMe2)5}FeH(Ph2P–PPh2)n (n = 1 or 2) have been obtained, which are both diamagnetic 18‐valence‐electron complexes. Two‐coordinated {C5(CHMe2)5}FeN(SiMe3)2 features sizeable negative magnetic anisotropy and slow magnetic relaxation with an effective energy barrier for spin reversal of 113 cm–1 under an applied field of 3000 Oe.
Pentaisopropylcyclopentadienyliron(II) bis(trimethylsilyl)amide is a versatile starting compound for the synthesis of diamagnetic or paramagnetic iron(II) half‐sandwich complexes. Reactions with water, 2,5‐dimethylpyrrole, and diphenylphosphine have been studied and the products are discussed, including the magnetic properties of the title complex.
CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with ...Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences.
•Complete information flow to consider travel time uncertainty in city logistics vehicle routing.•An innovative approach for robust routing in city logistics.•Applicability of interval travel times ...in conjunction with min–max regret evaluation.•Comprehensive case study based on real-world data for a representative city logistics vehicle routing setting.•Computational results show alternatives that are more robust, but also cost efficient.
We propose a consistent information flow to integrate Interval Travel Times (ITT) into a city logistics vehicle routing problem with satellites. The consistent information flow encompasses the derivation of ITT, the usage of ITT in robust shortest path computation and the integration of ITT into robust vehicle routing. Based on the results of the information flow, robust meeting times of first-tier and second-tier vehicles are created. We evaluate the approach with large real-world traffic data sets. We observe that the integration of ITT leads to first-tier routes that are reasonably efficient and robust.
Using synchrotron X-ray scattering, we investigate liquid Ge15Te85 spanning a wide temperature range from near Tg to the melt, and demonstrate that the density anomaly and fragile-strong transition ...are not only related to short-range-order (SRO) structural change (e.g. Peierls-like distortion), but also accompanied by a remarkable development of medium-range-order (MRO). The latter manifests as an emerging pre-peak in total structure factor S(Q) and atomic pair correlations on the length scale of ∼8 Å in the real space G(r) function. The results highlight the role of medium-range structural ordering in the evolution of the configurational entropy which, according to the Adam-Gibbs theory, can be linked to the fragile-strong transition (FS-transition). Based on the relation between structure and liquid dynamics, the FS-transitions at high pressures are examined in terms of experimental data and the Ehrenfest relation. This work identifies the length scale for the atomic correlations in MRO structural evolutions and presents a structural approach to exploring liquid dynamics, which may be useful for investigating relevant phase-change alloys.
Display omitted
PDF
