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Background: Early studies in cellular models suggested an iron accumulation in Friedreich's ataxia (FA), yet findings from patients are lacking. Objectives: The objective is to characterize systemic iron metabolism, body iron storages, and intracellular iron regulation in FA patients. Methods: In FA patients and matched healthy controls, we assessed serum iron parameters, regulatory hormones as well as the expression of regulatory proteins and iron distribution in peripheral blood mononuclear cells (PBMCs). We applied magnetic resonance imaging with R2*‐relaxometry to quantify iron storages in the liver, spleen, and pancreas. Across all evaluations, we assessed the influence of the genetic severity as expressed by the length of the shorter GAA‐expansion (GAA1). Results: We recruited 40 FA patients (19 women). Compared to controls, FA patients displayed lower serum iron and transferrin saturation. Serum ferritin, hepcidin, mean corpuscular hemoglobin and mean corpuscular volume in FA inversely correlated with the GAA1‐repeat length, indicating iron deficiency and restricted availability for erythropoiesis with increasing genetic severity. R2*‐relaxometry revealed a reduction of splenic and hepatic iron stores in FA. Liver and spleen R2* values inversely correlated with the GAA1‐repeat length. FA PBMCs displayed downregulation of ferritin and upregulation of transferrin receptor and divalent metal transporter‐1 mRNA, particularly in patients with >500 GAA1‐repeats. In FA PBMCs, intracellular iron was not increased, but shifted toward mitochondria. Conclusions: We provide evidence for a previously unrecognized iron starvation signature at systemic and cellular levels in FA patients, which is related to the underlying genetic severity. These findings challenge the use of systemic iron lowering therapies in FA. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Various types of digital dental technologies have been successfully implemented as a part of dental treatment to improve predictability and efficiency of dental procedures. Virtual smile design can be used to enhance predictability from an esthetic perspective, and the virtual articulator can be a useful tool to create a desired occlusal scheme. This case series describes a fully digital workflow that can predictably achieve desired esthetic and functional outcomes. The proposed protocol also includes other currently available digital technologies, such as intraoral scanning, computer-aided design, milling, and 3D printing. [ABSTRACT FROM AUTHOR]

Throughfall heterogeneity induced by the redistribution of precipitation in vegetation canopies has repeatedly been hypothesized to affect the variation of soil water content and runoff behavior, especially in forests. However, we are not aware of any observational study relating the spatial variation of soil water content directly to net precipitation to confirm modelling hypotheses. Here, we investigate whether throughfall patterns affect the spatial heterogeneity of soil water response in the main rooting zone. We assessed rainfall, throughfall and soil water contents (two depths: 7.5 cm and 27.5 cm) on a 1-ha temperate mixed beech forest plot in Germany 2015 - 2016 during the growing seasons in independent high-resolution stratified random designs. Because throughfall and soil water content cannot be measured at the same location, we used kriging to derive the throughfall values at the locations where soil water content was measured. We first explore the spatial variation and temporal stability of throughfall and soil water patterns, and next evaluate the effects of input (throughfall), soil properties (field capacity and air capacity), and vegetation parameters (canopy cover and distance to the next tree) on soil water content and dynamics. Throughfall spatial patterns were related to canopy density. Although spatial auto-correlation decreased with increasing event sizes, temporally stable throughfall patterns emerged, leading to reoccurring high and lower input locations across precipitation events. A linear mixed effect model analysis showed, that soil water content patterns were only poorly linked to throughfall spatial patterns, and it was rather shaped by unidentified but time constant factors. Instead of soil water content itself, the patterns of its increase after rainfall corresponded more closely to throughfall patterns, in that more water was stored in the soil where throughfall was elevated. Furthermore, soil moisture patterns themselves enhanced or decreased water storage in the soil, and probably fast drainage and runoff components. Locations with low topsoil water content tended to store less of the input water, indicating preferential flow. In contrast in subsoil, locations with high water content stored less water. Also, distance to the next tree and air capacity modified how much water was retained in soil storage. In this comprehensive study we show that throughfall patterns imprint less on soil water contents and more on soil water dynamics shortly after rainfall events, therefore only partly confirming previous modelling with data. Our findings highlight at the same time systematic patterns of times and locations where the capacity to store water is reduced and water probably conducted quickly to greater depth. Our results indicate that not soil moisture patterns but rather percolation may depend on small scale spatial heterogeneity of canopy input patterns. [ABSTRACT FROM AUTHOR]

Background: Women with Li‐Fraumeni syndrome (LFS) have elevated breast cancer (BC) risk. Optimal BC treatment strategies in this population are yet unknown. Methods: BC subtypes and treatment were retrospectively investigated between December 2016 and January 2019 in a multicentre study. BC risks were evaluated according to the type of surgery. Results: Thirty‐five women of our study population (35/44; 79.5%) had developed 36 breast lesions at first diagnosis at a mean age of 34 years. Those breast lesions comprised 32 invasive BCs (89%), three ductal carcinoma in situ alone (8%) and one malignant phyllodes tumour (3%). BCs were mainly high‐grade (18/32), of no special type (NST; 31/32), HER2‐enriched (11/32) or luminal‐B‐(like)‐type (10/32). Affected women (n = 35) received breast‐conserving surgery (BCS, n = 17) or a mastectomy (ME, n = 18) including seven women with simultaneous contralateral prophylactic mastectomy (CPM) at first diagnosis. Nineteen women suffered 20 breast or locoregional axillary lesions at second diagnosis with mean age of 36. Median time between first and second diagnosis was 57 months; median time to contra‐ and ipsilateral recurrence depended on surgical strategies (BCS: 46 vs. unilateral ME: 93 vs. bilateral ME > 140 months). Women with a primary treatment of solitaire therapeutic ME suffered from contralateral BC earlier compared to those with therapeutic ME and CPM (median: 93 vs. >140 months). Conclusion: Aggressive BC subtypes occur among women with LFS. Surgical treatment, i.e. ME and CPM, may prolong time to a second BC diagnosis. Conclusion on long‐term survival benefit is pending. Individual competing tumour risks and long‐term outcomes need to be taken into consideration. [ABSTRACT FROM AUTHOR]

Iron is an essential co-factor for many cellular metabolic processes, and mitochondria are main sites of utilization. Iron accumulation promotes production of reactive oxygen species (ROS) via the catalytic activity of iron species. Herein, we investigated the consequences of dietary and genetic iron overload on mitochondrial function. C57BL/6N wildtype and Hfe−/− mice, the latter a genetic hemochromatosis model, received either normal diet (ND) or high iron diet (HI) for two weeks. Liver mitochondrial respiration was measured using high-resolution respirometry along with analysis of expression of specific proteins and ROS production. HI promoted tissue iron accumulation and slightly affected mitochondrial function in wildtype mice. Hepatic mitochondrial function was impaired in Hfe−/− mice on ND and HI. Compared to wildtype mice, Hfe−/− mice on ND showed increased mitochondrial respiratory capacity. Hfe−/− mice on HI showed very high liver iron levels, decreased mitochondrial respiratory capacity and increased ROS production associated with reduced mitochondrial aconitase activity. Although Hfe−/− resulted in increased mitochondrial iron loading, the concentration of metabolically reactive cytoplasmic iron and mitochondrial density remained unchanged. Our data show multiple effects of dietary and genetic iron loading on mitochondrial function and linked metabolic pathways, providing an explanation for fatigue in iron-overloaded hemochromatosis patients, and suggests iron reduction therapy for improvement of mitochondrial function. [ABSTRACT FROM AUTHOR]

• Rh supported large pore Zr-MOFs with different pore structure were prepared and characterized. • The catalysts show markedly different catalytic effects in the hydroformylation reaction with different framework types. • All catalysts show superior activity at low rh content as expected from rh single site catalysts. • A markedly impact of the pore structure on selectivity to aldehydes and enones is observed. • Catalytic differences are due to different accessibility of rh located in various framework sites. Three large pore crystalline zirconium-based metal-organic frameworks (Zr-MOFs) of different pore sizes (6–18 Å) and structure were synthesized and used for the preparation of the Rh-supported catalysts Rh@UiO-66, Rh@UiO-67, and Rh@MOF-808. The materials were characterized by XRD, FTIR, SEM/TEM, XPS, and nitrogen adsorption/desorption measurements. The catalytic performance was studied in the hydroformylation of olefins to the corresponding aldehydes. A series of n-alk-1-enes of different chain length was used to study the influence of the pore size and structure. The results show that the Zr-MOF-based catalysts are very active and show high aldehyde selectivity. The superior catalytic properties are assigned to the presence of highly dispersed active Rh sites located at the isolated zirconia moieties and the enhanced accessibility of sites via the large pores. Nevertheless, marked differences in the catalytic performance of the catalysts are observed, which are assigned to the different accessibility of Rh located at various secondary building units. [Display omitted] [ABSTRACT FROM AUTHOR]

Anemia is a major health issue and associated with increased morbidity. Iron deficiency anemia (IDA) is the most prevalent, followed by anemia of chronic disease (ACD). IDA and ACD often co-exist, challenging diagnosis and treatment. While iron supplementation is the first-line therapy for IDA, its optimal route of administration and the efficacy of different repletion strategies in ACD are elusive. Female Lewis rats were injected with group A streptococcal peptidoglycan-polysaccharide (PG-APS) to induce inflammatory arthritis with associated ACD and/or repeatedly phlebotomized and fed with a low iron diet to induce IDA, or a combination thereof (ACD/IDA). Iron was either supplemented by daily oral gavage of ferric maltol or by weekly intravenous (i.v.) injection of ferric carboxymaltose for up to 4 weeks. While both strategies reversed IDA, they remained ineffective to improve hemoglobin (Hb) levels in ACD, although oral iron showed slight amelioration of various erythropoiesis-associated parameters. In contrast, both iron treatments significantly increased Hb in ACD/IDA. In ACD and ACD/IDA animals, i.v. iron administration resulted in iron trapping in liver and splenic macrophages, induction of ferritin expression and increased circulating levels of the iron hormone hepcidin and the inflammatory cytokine interleukin-6, while oral iron supplementation reduced interleukin-6 levels. Thus, oral and i.v. iron resulted in divergent effects on systemic and tissue iron homeostasis and inflammation. Our results indicate that both iron supplements improve Hb in ACD/IDA, but are ineffective in ACD with pronounced inflammation, and that under the latter condition, i.v. iron is trapped in macrophages and may enhance inflammation.