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Alzheimer's disease (AD) is a highly prevalent multifactorial disease for which Diabetes Mellitus (DM) is a risk factor. Abnormal phosphorylation and aggregation of tau is a key hallmark of AD. In animal models, DM induces or exacerbates the phosphorylation of tau, suggesting that DM may influence the risk at AD by directly facilitating tau pathology. Previously we reported that tau phosphorylation induced in response to metabolic stress is reversible. Since identification and understanding of early players in tau pathology is pivotal for therapeutic intervention, we here investigated the mechanism underlying tau phosphorylation in the diabetic brain and its potential for reversibility. To model DM we used streptozotocin-treatment to induce insulin deficiency in rats. Insulin depletion leads to increased tau phosphorylation in the brain and we investigated the activation status of known tau kinases and phosphatases in this model. We identified protein kinase A (PKA) as a tau kinase activated by DM in the brain. The potential relevance of this signaling pathway to AD pathogenesis is indicated by the increased level of active PKA in temporal cortex of early stage AD patients. Our data indicate that activation of PKA and tau phosphorylation are associated with insulin deficiency per se , rather than the downstream energy deprivation. In vitro studies confirm that insulin deficiency results in PKA activation and tau phosphorylation. Strikingly, both active PKA and induced tau phosphorylation are reversed upon insulin treatment in the steptozotocin animal model. Our data identify insulin deficiency as a direct trigger that induces the activity of the tau kinase PKA and results in tau phosphorylation. The reversibility upon insulin treatment underscores the potential of insulin as an early disease-modifying intervention in AD and other tauopathies. [ABSTRACT FROM AUTHOR]

Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response. [ABSTRACT FROM AUTHOR]

To determine the impact of increased glucose concentration on gene expression of primary healthy human limbal fibroblasts (LFCs) and congenital aniridia human limbal fibroblasts (AN-LFCs), in vitro. LFCs (n = 8) and AN-LFCs (n = 8) were isolated and cultured in serum containing DMEM, including either normal glucose (17.5 mM) or increased glucose (70 mM) concentration for 48h or 72h, respectively. mRNA and protein expression of transforming growth factor beta 1 (TGF-β1), alpha-smooth muscle actin (ACTA)2A1, SMAD 2/3, hypoxia markers such as nuclear factor kappa B (NFκB), inducible nitric oxide synthase (iNOS), hypoxia-inducible factor 1-alpha (HIF-1ɑ), oxidative stress markers such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Catalase (CAT) were analyzed using qPCR and Western blot. In 70 mM glucose concentration medium for 48 h, TGF-β1 mRNA expression was significantly lower (p = 0.001, p < 0.001), Nrf2 (p = 0.001, p = 0.001) and CAT (p = 0.001, p = 0.001) mRNA expression was significantly higher in LFCs and AN-LFCs, than using 17.5 mM glucose concentration medium. In addition, in 70 mM glucose concentration medium for 48 h, SMAD 2 , SMAD 3 , NFκB , HIF-1ɑ mRNA expression was significantly lower in AN-LFCs, than in 17.5 mM glucose concentration medium (p = 0.003, p = 0.002, p = 0.008, p = 0.020). At this time-point in 70 mM glucose concentration medium, at protein level, TGF-β1, SMAD2/3 and NFκB were significantly lower in AN-LFCs, than in 17.5 mM glucose concentration medium (p = 0.041, p = 0.002, p = 0.012). In 70 mM glucose concentration medium for 72h, TGF-β1 was significantly higher (p < 0.001, p < 0.001) and Nrf2 (p = 0.001, p = 0.001) and CAT (p < 0.001, p < 0.001) mRNA were significantly lower in LFCs and AN-LFCs, than in 17.5 mM glucose concentration medium. At this time-point, in 70 mM glucose concentration medium, NFκB mRNA was significantly higher (p < 0.001) in LFCs , than in 17.5 mM glucose concentration DMEM medium. In 70 mM glucose concentration medium for 72 h, TGF-β1 and NFκB protein were significantly lower in AN-LFCs, than in 17.5 mM glucose concentration medium (p < 0.001, p < 0.001). Our study confirmed that high glucose concentration has an impact on TGF-β1 and NFκB signaling both in AN-LFCs and LFCs. These findings highlight that prolonged exposure to high glucose levels may contribute to cellular stress and dysfunction in LFCs and AN-LFCs. • This study demonstrates that elevated glucose concentrations lead to alterations in the transforming growth factor-beta (TGF-β) signaling pathway in both limbal fibroblast cells (LFCs) and aniridia limbal fibroblast cells (AN-LFCs). • High glucose concentration induces hypoxia in both LFCs and AN-LFCs when compared to normal glucose levels. The TGF-β1 signaling pathway and hypoxic responses exhibit greater sensitivity to increased glucose concentrations in AN-LFCs than in healthy controls. • Paired box protein 6 (PAX6) mRNA levels in AN-LFCs are significantly upregulated after 72 h of exposure to elevated glucose concentrations. • Both LFCs and AN-LFCs are susceptible to oxidative stress induced by 48 h of exposure to high glucose concentrations; however, this response may be mitigated after 72 h. • This study underscores the critical role of glucose metabolism in LFCs and AN-LFCs and suggests that elevated glucose levels may contribute to the pathogenesis of aniridia-associated keratopathy. [ABSTRACT FROM AUTHOR]

Purpose: To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls.Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2 years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7 years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4 years). Main outcome parameters were the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, and their difference (A-V SO2; %) recorded with the oxygen saturation tool of the Retinal Vessel Analyzer (IMEDOS Systems UG, Germany). Statistical analyses were performed with linear mixed-effects models.Eyes suffering from CHM differed significantly from both RP and control eyes, when the retinal oxygen metabolic parameters were taken into account. While RP showed significantly higher A-SO2 and V-SO2 values when compared to controls, CHM showed opposite findings with significantly lower values when compared to both RP and controls (P < 0.001). The A-V SO2, which represents the retinal oxygen metabolic consumption, showed significantly lower values in CHM compared to controls.The retina in CHM is a relatively hypoxic environment. The decrease in oxygen levels may be due to the profound choroidal degeneration, leading to decreased oxygen flux to the retina. RO measurements may help understand the pathogenesis of CHM and RP. These findings may provide useful details to inform the planning of clinical trials of emerging therapies for CHM.What was known before?Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.What this study adds:RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.Methods: To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls.Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2 years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7 years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4 years). Main outcome parameters were the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, and their difference (A-V SO2; %) recorded with the oxygen saturation tool of the Retinal Vessel Analyzer (IMEDOS Systems UG, Germany). Statistical analyses were performed with linear mixed-effects models.Eyes suffering from CHM differed significantly from both RP and control eyes, when the retinal oxygen metabolic parameters were taken into account. While RP showed significantly higher A-SO2 and V-SO2 values when compared to controls, CHM showed opposite findings with significantly lower values when compared to both RP and controls (P < 0.001). The A-V SO2, which represents the retinal oxygen metabolic consumption, showed significantly lower values in CHM compared to controls.The retina in CHM is a relatively hypoxic environment. The decrease in oxygen levels may be due to the profound choroidal degeneration, leading to decreased oxygen flux to the retina. RO measurements may help understand the pathogenesis of CHM and RP. These findings may provide useful details to inform the planning of clinical trials of emerging therapies for CHM.What was known before?Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.What this study adds:RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.Results: To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls.Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2 years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7 years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4 years). Main outcome parameters were the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, and their difference (A-V SO2; %) recorded with the oxygen saturation tool of the Retinal Vessel Analyzer (IMEDOS Systems UG, Germany). Statistical analyses were performed with linear mixed-effects models.Eyes suffering from CHM differed significantly from both RP and control eyes, when the retinal oxygen metabolic parameters were taken into account. While RP showed significantly higher A-SO2 and V-SO2 values when compared to controls, CHM showed opposite findings with significantly lower values when compared to both RP and controls (P < 0.001). The A-V SO2, which represents the retinal oxygen metabolic consumption, showed significantly lower values in CHM compared to controls.The retina in CHM is a relatively hypoxic environment. The decrease in oxygen levels may be due to the profound choroidal degeneration, leading to decreased oxygen flux to the retina. RO measurements may help understand the pathogenesis of CHM and RP. These findings may provide useful details to inform the planning of clinical trials of emerging therapies for CHM.What was known before?Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.What this study adds:RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.Conclusion: To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls.Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2 years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7 years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4 years). Main outcome parameters were the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, and their difference (A-V SO2; %) recorded with the oxygen saturation tool of the Retinal Vessel Analyzer (IMEDOS Systems UG, Germany). Statistical analyses were performed with linear mixed-effects models.Eyes suffering from CHM differed significantly from both RP and control eyes, when the retinal oxygen metabolic parameters were taken into account. While RP showed significantly higher A-SO2 and V-SO2 values when compared to controls, CHM showed opposite findings with significantly lower values when compared to both RP and controls (P < 0.001). The A-V SO2, which represents the retinal oxygen metabolic consumption, showed significantly lower values in CHM compared to controls.The retina in CHM is a relatively hypoxic environment. The decrease in oxygen levels may be due to the profound choroidal degeneration, leading to decreased oxygen flux to the retina. RO measurements may help understand the pathogenesis of CHM and RP. These findings may provide useful details to inform the planning of clinical trials of emerging therapies for CHM.What was known before?Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.What this study adds:RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.Key messages: To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls.Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2 years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7 years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4 years). Main outcome parameters were the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, and their difference (A-V SO2; %) recorded with the oxygen saturation tool of the Retinal Vessel Analyzer (IMEDOS Systems UG, Germany). Statistical analyses were performed with linear mixed-effects models.Eyes suffering from CHM differed significantly from both RP and control eyes, when the retinal oxygen metabolic parameters were taken into account. While RP showed significantly higher A-SO2 and V-SO2 values when compared to controls, CHM showed opposite findings with significantly lower values when compared to both RP and controls (P < 0.001). The A-V SO2, which represents the retinal oxygen metabolic consumption, showed significantly lower values in CHM compared to controls.The retina in CHM is a relatively hypoxic environment. The decrease in oxygen levels may be due to the profound choroidal degeneration, leading to decreased oxygen flux to the retina. RO measurements may help understand the pathogenesis of CHM and RP. These findings may provide useful details to inform the planning of clinical trials of emerging therapies for CHM.What was known before?Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa.What this study adds:RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.RO function in choroideremia is significantly altered when compared to controls.Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa.By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia. [ABSTRACT FROM AUTHOR]

PAX6 haploinsufficiency related aniridia is characterized by disorder of limbal epithelial cells (LECs) and aniridia related keratopathy. In the limbal epithelial cells of aniridia patients, deregulated retinoic acid (RA) signaling components were identified. We aimed to visualize differentiation marker and RA signaling component expression in LECs, combining a differentiation triggering growth condition with a small interfering RNA (siRNA) based aniridia cell model (PAX6 knock down). Primary LECs were isolated from corneoscleral rims of healthy donors and cultured in serum free low Ca2+ medium (KSFM) and in KSFM supplemented with 0.9 mmol/L Ca2+. In addition, LECs were treated with siRNA against PAX6. DSG1, PAX6, KRT12, KRT 3, ADH7, RDH10, ALDH1A1, ALDH3A1, STRA6, CYP1B1, RBP1, CRABP2, FABP5, PPARG, VEGFA and ELOVL7 expression was determined using qPCR and western blot. DSG1, FABP5, ADH7, ALDH1A1, RBP1, CRABP2 and PAX6 mRNA and FABP5 protein expression increased (p ≤ 0.03), PPARG, CYP1B1 mRNA expression decreased (p ≤ 0.0003) and DSG1 protein expression was only visible after Ca2+ supplementation. After PAX6 knock down and Ca2+ supplementation, ADH7 and ALDH1A1 mRNA and DSG1 and FABP5 protein expression decreased (p ≤ 0.04), compared to Ca2+ supplementation alone. Using our cell model, with Ca2+ supplementation and PAX6 knockdown with siRNA treatment against PAX6, we provide evidence that haploinsufficiency of the master regulatory gene PAX6 contributes to differentiation defect in the corneal epithelium through alterations of RA signalling. Upon PAX6 knockdown, DSG1 differentiation marker and FABP5 RA signaling component mRNA expression decreases. A similar effect becomes apparent at protein level though differentiation triggering Ca2+ supplementation in the siRNA-based aniridia cell model. Expression data from this cell model and from our siRNA aniridia cell model strongly indicate that FABP5 expression is PAX6 dependent. These new findings may lead to a better understanding of differentiation processes in LECs and are able to explain the insufficient cell function in AAK. • PAX6 , DSG1 and RA signaling component FABP5 expression is significantly upregulated in presence of Ca2+ in LECs. • DSG1 protein expression is only visible under Ca2+ growth conditions, proving enhanced differentiation in LECs through Ca2+. • Ca2+ supplementation can be combined with PAX6 siRNA treatment to mimic aniridia cellular behavior observed in patients. • DSG1 and FABP5 seem to be PAX6 dependent or driven by PAX6 in LECs. [ABSTRACT FROM AUTHOR]

The isomorphous substitution of Al 3 + and/or Fe 3 + cations into the erionite zeolite framework were studied through periodic density functional theory computations. Taking as reference the Mulliken charges for siliceous framework computed in previous work (Antúnez-García et al. in J Mol Struct 1059:232–238, 2014), the present results show that the basicity of ERI zeolite increases when those cations are introduced into the framework. It was also observed that when at least two Si 4 + cations are isomorphically substituted by Fe 3 + in the unit cell of the erionite zeolite, it acquires magnetic properties. The results show that a specific net-spin polarization (up or down) could be correlated with particular configurations of erionite zeolite, containing ferric iron. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondrial dysfunction in CKD are not entirely known. The purpose of this study was to define the impact of uremic metabolites on mitochondrial energetics. Skeletal muscle mitochondria were isolated from C57BL/6N mice and exposed to vehicle (DMSO) or varying concentrations of uremic metabolites: indoxyl sulfate, indole- 3-acetic-acid, L-kynurenine, and kynurenic acid. A comprehensive mitochondrial phenotyping platform that included assessments of mitochondrial oxidative phosphorylation (OXPHOS) conductance and respiratory capacity, hydrogen peroxide production (JH2O2), matrix dehydrogenase activity, electron transport system enzyme activity, and ATP synthase activity was employed. Uremic metabolite exposure resulted in a ~25-40% decrease in OXPHOS conductance across multiple substrate conditions (P < 0.05, n = 5-6/condition), as well as decreased ADP-stimulated and uncoupled respiratory capacity. ATP synthase activity was not impacted by uremic metabolites; however, a screen of matrix dehydrogenases indicated that malate and glutamate dehydrogenases were impaired by some, but not all, uremic metabolites. Assessments of electron transport system enzymes indicated that uremic metabolites significantly impair complex III and IV. Uremic metabolites resulted in increased JH2O2 under glutamate/malate, pyruvate/malate, and succinate conditions across multiple levels of energy demand (all P < 0.05, n = 4/group). Disruption of mitochondrial OXPHOS was confirmed by decreased respiratory capacity and elevated superoxide production in cultured myotubes. These findings provide direct evidence that uremic metabolites negatively impact skeletal muscle mitochondrial energetics, resulting in decreased energy transfer, impaired complex III and IV enzyme activity, and elevated oxidant production. [ABSTRACT FROM AUTHOR]

Abstract PAX6-related Aniridia is a sight-threatening disease involving progression of secondary glaucoma and aniridia related keratopathy (ARK). Change or loss of limbal epithelial progenitors causes epithelial surface defects. We analyzed the effect of PAX6 on mRNA expression changes with a two-step approach, as follows. First, we sequenced mRNA from limbal epithelial cells isolated from controls and aniridia patients. Second, we confirmed the bioinformatics and literature-based result list for a small interfering RNA (siRNA)-based primary aniridia cell model (PAX6 knockdown). With this approach, we expected that the genes directly influenced by PAX6 would be distinguishable from those affected secondarily by the ARK disease state. Therefore, epithelial cells were isolated from the limbus region of two patients with aniridia and cultured in keratinocyte serum-free medium. Normal control cells were obtained from the limbus region of corneal donors. For the siRNA-based aniridia cell model, cells were transfected with Lipofectamine and 5 nM siRNA against PAX6 or control treatment. All cells were lysed to yield DNA, RNA, and protein. Reduction of PAX6 protein was assessed by western blot. Aniridia and control Poly-A–enriched RNA libraries were subjected to next-generation sequencing. The differential analysis was a combination of quantification with RSEM and differential tests with edgeR. Gene lists were filtered by comparison to NCBI GEO datasets, annotated with DAVID, and manually annotated using a literature search. Based on the resulting filtered gene list, qPCR primers were purchased, and candidate genes (TP63 , ABCG2 , ADH7 , ALDH1A1 , PITX1 , DKK1 , DSG1 , KRT12 , KRT3 , KRT13 , SPINK6 , SPINK7 , CTSV , SERPINB1) were verified by qPCR on the siRNA-based aniridia cell model. We identified genes that might be regulated by PAX6 and showed that SPINK7 mRNA, which codes for a protease inhibitor, is downregulated in patients as well as in our primary aniridia cell model. ALDH1A1 and AHD7 mRNA levels were reduced in limbal epithelial cells of aniridia patients, and both transcripts were downregulated by PAX6 knockdown in our cell model. This siRNA-based aniridia cell model is a valuable tool for confirming identified PAX6-affected genes that might promote ARK pathogenesis. The model recapitulated expression changes for SPINK7 , ADH7 , and ALDH1A1 that were also observed in patient samples. These results provide evidence that PAX6 might drive corneal epithelial differentiation by direct or indirect control of retinoic acid signaling processes through ADH7 and ALDH1A1. Highlights • PAX6 has an important influence on the differentiation process of limbal epithelial (stem) cells. • PAX6 siRNA model recapitulates differentiation defects of aniridia limbal epithelial cells. • Retinoic acid signaling components are potentially PAX6 related. • SPINK protease inhibitors are downregulated in aniridia limbal epithelial cells. [ABSTRACT FROM AUTHOR]

Congenital aniridia is a rare panocular disease in which almost all structures of the eye are affected. The observed corneal abnormalities are called aniridia‐associated keratopathy (AAK). AAK is characterized by progressive limbal stem cell deficiency (LSCD), epithelial thinning and erosions, corneal ulceration, vascularization, inflammation and pannus formation. Although in some aspects AAK resembles other types of LSCD, through its specific genetic origin, alterations in corneal epithelial cell gene expression differ from other types of corneal diseases. Primary limbal epithelial cells of aniridia subjects lack expression of KRT3 and KRT12 mRNA and protein, and DSG1, ADH7, FABP5, CRABP2, SPINK7 and ALDH1A1 mRNA expression is decreased in these cells. However, miRNA 138‐5p expression is upregulated. This epithelial behaviour can also be mimicked using an siRNA based aniridia primary limbal epithelial cell model. [ABSTRACT FROM AUTHOR]

Congenital aniridia is a rare panocular disease in which almost all structures of the eye are affected. The observed corneal abnormalities are called aniridia‐associated keratopathy (AAK). AAK is characterized by progressive limbal stem cell deficiency (LSCD), epithelial thinning and erosions, corneal ulceration, vascularization, inflammation and pannus formation. Although in some aspects AAK resembles other types of LSCD, through its specific genetic origin, alterations in corneal epithelial cell gene expression differ from other types of corneal diseases. Primary limbal epithelial cells of aniridia subjects lack expression of KRT3 and KRT12 mRNA and protein, and DSG1, ADH7, FABP5, CRABP2, SPINK7 and ALDH1A1 mRNA expression is decreased in these cells. However, miRNA 138‐5p expression is upregulated. This epithelial behaviour can also be mimicked using an siRNA based aniridia primary limbal epithelial cell model. [ABSTRACT FROM AUTHOR]

Objectives The nutrition and physical activity transitions, characterized by increased consumption of high energy density foods and more sedentary lifestyles, are associated with increased obesity and hypertension in Ecuador. These transitions have been characterized primarily in urban areas, which may neglect variation in specific rural areas of Ecuador. Therefore we examined the extent of the differences in dietary and activity patterns, obesity prevalence, and blood pressure (BP) in urban and rural-dwelling women in the Ecuadorian central highlands. Methods Urban-dwelling women (UW, n = 198, mean age = 44 years) from three areas of a city of 250,000 residents and rural women (RW; n = 202, mean age = 47 years) from three remote communities in the same province (Chimborazo) were randomly selected and surveyed for dietary and activity practices, BP, and anthropometrics. Results Ninety percent of UW reported obtaining their food primarily from markets while 65% of RW women obtained their food primarily from their own cultivation. Cookies, cakes, candies, ice cream, and French fries were consumed more frequently by UW. RW reported lower consumption of beef, poultry, and chicken, as well as fruits, milk, and white rice. UW compared to RW women spent less time walking and in strenuous work activities. Obesity (BMI > 30 kg/m2) (UW = 18.7% vs RW = 9.2%) and hypertension (UW = 15.7%, RW= 3.0%) were more common in UW. Average systolic and diastolic BP was significantly higher in UW. Conclusions The nutrition and physical activity transitions appear more evident in urban- compared to rural-dwelling women, and are associated with more obesity and higher BP. [ABSTRACT FROM AUTHOR]

The measurement of 3D spatial coordinates for model reconstruction through artificial machine vision systems based on optical sensors and the corresponding signal processing associated with algorithms is a powerful module for cyber systems. It provides an efficient, functional, and intelligent vision and data information of the objects and scenes under observation for decisions, as well as for remote environment interactivity and autonomous robot systems actuation. Over the past 20 years, the artificial machine vision has benefited from emerging technology and a promising huge potential is peeking out, but also technical difficulties achieving customized and true commercial applications. This paper reviews the research progress, trends, and future research directions; the state-of-the-art of topics related to the 3D spatial measurement for model reconstruction. It classifies the technology by its fundamental principles and applications, to construct an outlook about its advantages, disadvantages, and challenges. • Topics related to the 3D spatial measurement for model reconstruction. • Review of the research progress and the state of the art of topics. • State of the art and the fundamental principles of topics detailed explanation. • Description of technologies and applications are presented. • Classification of technology based on optical sensors and its signal processing. • Technology outlook construction advantages, disadvantages, advances, and challenges. • This literature point out the emergence and boost the machine vision for innovation. • Machine vision based cyber-systems contribution to industry 4.0. • Literature for promotion and encourage of research in related fields. [ABSTRACT FROM AUTHOR]

The electronic properties of various cationic forms of MFI type lamellar zeolites were studied using DFT calculations and compared with their bulk counterparts. In this study, Na+ and H+ cations were considered for the effect of charge deficit compensation on the surface of lamellar zeolites. The results show that lamellar zeolites in different cationic forms exhibit two distinct band gap widths, whose values are lower than those of their bulk counterparts and arise from the surface atoms. Furthermore, the results suggest that the Na+ cation behaves as a structure-directing agent on the surface, while H+ passivates the surface of the lamellar zeolites. [Display omitted] • Compared to the bulk, the lamellar zeolites presented two different bandgaps. • The H+ cations have a passivating function on the surface of the lamellar zeolites. • The nature of the Na+ cations on the surface is that of structure directing agent. [ABSTRACT FROM AUTHOR]

In the current research, podometry vision system (PVS) and classification method are developed as alternative ionizing radiation free system for the classification of different foot malformations. PVS is composed of one scanning unit and one load distribution unit, which measure anthropometric angles and the load distribution. The obtained measurements enable the application of the proposed method, which classifies the foot type and rearfoot in accordance with the anthropometric measurements and load distribution. The method provides a detailed classification of the cavus foot as posterior, mixed and anterior. Anterior can be divided as direct and intern depending on the symmetry of the 1st metatarsal and 5th metatarsal. The PVS and method can be used as a tool to analyze the evolution of the foot in response to the treatments indicated by the medical professional. On the other hand, the obtained results coincide with the classification provided by a medical professional. Moreover, the measurements provide additional information on the rearfoot deviation and load distribution. • Podometry vision system measures anthropometric angles and load distribution. • Foot types classification based on anthropometric and load measurements. • System free of ionizing-radiation to characterize the foot types. • The system provides a detailed classification of the cavus foot. • The system can be used as a tool for comparison of functional and clinical tests. [ABSTRACT FROM AUTHOR]

On the basis of the density functional theory (DFT) calculations, the successive isomorphic substitution of one to six tetrahedrally coordinated Si cations by trivalent Al was systematically studied. As a result of exploring a significant number of configurations, without using a priori assumptions, it was found that the Al atoms are accommodated according to the ground state sequence in the tetrahedral sites T I ​− ​T III ​− ​T III ​− ​T I ​− ​T III ​− ​T III. The results in the general show: a) Al cations preferentially occupy T III positions, b) the distribution of cations in the framework does not violate Löwenstein's rule, c) the distribution of cations in the framework does not satisfy Dempsey's rule, and d) only one Al cation is found per ζ -cage. Self-assembling of mordenite structural motifs. [Display omitted] • Found the minimum energy positions of 1 to 6 aluminum atoms in mordenite zeolite. • Aluminum atoms preferentially occupy T III sites. • The distribution of the aluminum atoms does not violate Löwenstein's rule. • Only one aluminum atom is found per ζ-cage. [ABSTRACT FROM AUTHOR]

[Display omitted] • The electronic properties of the LTA-type zeolites were studied by DFT computations. • Non-Löwensteinian configuration is energetically more favorable preferred for the aluminized framework. • For the ferric frameworks, theoretical results predicts a magnetic behavior. The electronic properties of LTA-type zeolites in their siliceous, aluminized, and ferric frameworks compositions, all of which were selected in their sodium ion-exchange form and under anhydrous conditions, were studied through DFT computations. In the case of an aluminized framework, it was found that the non-Löwensteinian configuration is not only energetically more favorable but also has better electronic conductivity than the Löwensteinian framework. The two different ferric frameworks under consideration presented distinct magnetic nature and higher acidity compared to aluminized ones. Furthermore, it was observed that the purely siliceous LTA framework presented an inversion in the Löwdin charge trace behavior, suggesting that it is associated with its hydrophobic nature. [ABSTRACT FROM AUTHOR]

Introduction: Congenital aniridia is increasingly recognized as part of a complex syndrome with numerous ocular developmental anomalies and non-ocular systemic manifestations. This requires comprehensive care and treatment of affected patients. Our purpose was to analyze systemic diseases in patients with congenital aniridia within the Homburg Aniridia Registry., Methods: Our retrospective, monocentric study included patients who underwent a comprehensive ophthalmic examination at Saarland University Medical Center beginning in June 2003. Age, gender, genetic test results, and information on systemic anomalies were recorded. In addition, parents and affected patients were interviewed about developmental and other disease-related conditions., Results: Data from 337 patients (mean age 22 ± 20 [0.3-90] years; 181 women [53.7%]) were analyzed. Genetic testing was performed in 187 (55.5%) patients. A PAX6 mutation was detected in 174 of 187 (93%) cases, of which 20 (10.7%) had WAGR(O) syndrome. Systemic diseases were detected in 155 of 337 (46%) patients, with the most common being obesity (29 [8.6%]), thyroid disease (28 [8.3%]), hypertension (26 [7.7%]), intellectual disability (22 [6.5%]), diabetes mellitus (19 [5.6%]), auditory perception disorder/speech development delay (16 [4.7%]), and epilepsy (12 [3.6%])., Conclusions: A comprehensive analysis of patients with aniridia and systemic effects reveals the complexity of this rare disorder, which goes beyond ocular symptoms and can have profound effects on metabolic balance, cardiovascular health, and the central nervous system. Therefore, early genetic diagnosis, early systemic checkup, and adequate treatment, as well as cooperation with pediatrists, neurologists, and audiologists, is suggested in congenital aniridia, which should be considered a syndrome and not an isolated ocular disease., Competing Interests: Declarations. Conflict of Interest: Jessica Obst, Fabian Norbert Fries, Maryam Amini, Annamária Náray, Cristian Munteanu, Tanja Stachon, Shweta Suiwal, Neil Lagali, Berthold Seitz, Barbara Käsmann-Kellner, and Nóra Szentmáry have no conflict of interests to declare. Nóra Szentmáry is an Editorial Board member of Ophthalmology and Therapy. Nóra Szentmáry was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: This study was approved by the Ethics Committee of Saarland (No. 144/15) and complied with the provisions of the Declaration of Helsinki and its amendments., (© 2025. The Author(s).)

Purpose: The potential risks and benefits of cataract surgery, in context of congenital aniridia (CA), are not widely understood, yet. Our purpose was to investigate the effect of lens properties on visual acuity (VA), aniridia-associated keratopathy (AAK) stage and presence of glaucoma at the Homburg Aniridia Center., Methods: CA subjects, examined at the Department of Ophthalmology of Saarland University between June 2003 and January 2022, were included. VA, slit-lamp examination, AAK grade, and glaucoma evaluation data were extracted from the medical records, from the first visit to the center. Eyes were categorized as clear lens, cataract, pseudophakic, aphakic, or subluxated lens. Patients were grouped by age (0-10, 10-20, 20-40, 40+ years)., Results: In 553 eyes of 286 CA subjects (age 19.9 ± 19.9 (0-83) years, 46.1% males), analysis revealed significant differences in VA and mean IOP (ANOVA p  < 0.0001; p  = 0.001, respectively) with lens status. Lens status was strongly associated with AAK Grade and glaucoma presence ( p  < 0.0001 for both). In age subgroups, AAK Stage was strongly associated with lens status in the 0-10 years ( p  < 0.001), 10-20 years ( p  < 0.001), and 40+ years ( p  = 0.02) groups and lens status was strongly associated with glaucoma presence in the 0-10 years ( p  = 0.003) and 20-40 years ( p  = 0.002) groups. AAK Stage was the most advanced in pseudophakic and aphakic eyes and presence of glaucoma was more pronounced in pseudophakic, aphakic and subluxated lens eyes., Conclusions: In a large population of CA, previous cataract surgery was associated with higher AAK Grade and presence of secondary glaucoma both in postoperatively pseudophakic and aphakic eyes. Our data indicate that caution is warranted with cataract surgery in congenital aniridia.

Research Highlights: IDS presented pathognomonic dilatation of the jejunum up to Meckel's diverticulum.IDS caused weight loss, decreased egg production, and increased culling and mortality.Chicken parvovirus (ChPV) was consistently detected through PCR assays.Chicken megrivirus (ChMV) was consistently detected through viral metagenomics.

Background and Objective: Volume-renderings of computed tomography or magnetic resonance angiograms (MRAs) are routinely used by surgeons in the preoperative assessment of vascular anatomy in kidney donors. Stereoscopic headsets (OST-HMD) like Microsoft HoloLens allow intuitive interaction with three-dimensional content for more intuitive comprehension, but do not allow real-time ray-casting volume-rendering of medical volume datasets on-device due to computational limitations., Methods: We introduce NEsted Semi-Transparent Isosurface Simulated Volume-Rendering (NESTIS-VR), as an on-device alternative to ray-casting volume-rendering and developed an application for HoloLens to render kidney donor MRAs with interactive control of fundamental rendering parameters. We compared NESTIS-VR with current standard pre-calculated 2D ray-cast volume-renderings in an observational study with 2 expert kidney transplant surgeons, measuring their confidence in pre-operatively assessing the kidney pedicle arterial anatomy in 20 potential donors. We also compared it against other 3D rendering techniques to understand which features contributed most to any improvements., Results: Real-time stereoscopic three-dimensional (3D) NESTIS-VR in Augmented Reality significantly improves surgeons' confidence compared with pre-calculated conventional two-dimensional (2D) ray-casting volume-rendered images (p = 0.0415/p = 0.00003). 2D non-stereoscopic NESTIS-VR was significantly superior to pre-calculated 2D ray-casting volume-rendered images for both surgeons (p = 0.044/p = 0.0003). Single isosurface 2D rendering was significantly superior than pre-calculated 2D volume-rendered images for one surgeon. There was no significant difference between binocular 3D display over 2D views with NESTIS-VR or between constrained and unconstrained vantage points for 2D viewing., Conclusion: NESTIS-VR provides a new approach to rendering medical datasets in computationally limited OST-HMD headsets and significantly increases surgeons' confidence of kidney donor arterial anatomy. The principal confidence benefit arises from providing surgeons interactive control over rendering parameters compared to pre-calculated renderings at preset parameters whilst rendering on-device and keeping the OST-HMD untethered from a workstation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bruce Daniel reports financial support was provided by GE Healthcare France. Fabian Necker reports a relationship with Siemens Healthineers that includes: employment. Fabian Necker was supported by BaCaTeC (Bavaria California Technology Center, Erlangen Germany) and is a scholarship holder at the Bavarian Research Institute for Digital Transformation (Munich, Germany), both institutions being funded by the Bavarian State Ministry for Science and Art. Christoph Leuze is Co-founder of Nakamir Inc, Menlo Park, CA., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro., Methods: Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7., Results: In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039)., Conclusions: The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media., (© 2024. The Author(s).)

Objective:  The aim of the study was to determine the effect of a short and long working length screw configuration on construct stiffness and plate strain in a synthetic, short fragment, small gap fracture model stabilized with a 12-hole 3.5-mm locking compression plate (LCP)., Study Design:  Six replicates of short and long working length constructs on a short fragment, small gap fracture model underwent four-point bending. Construct stiffness and plate strain were compared across working length and along the plate., Results:  With the LCP on the compression surface (compression bending), the short working length had a significantly higher construct stiffness and lower plate strain than the long working length. Conversely, with the LCP on the tension surface (tension bending), transcortical contact between 150 and 155 N induced load sharing at the fracture gap, which significantly increased construct stiffness and decreased plate strain in the long working length. At 100 N (precontact), the short working length had a significantly higher construct stiffness and lower plate strain than the long working length, comparable with our compressing bending results., Conclusion:  In compression bending, and before transcortical contact occurred in tension bending, the short working length had a significantly higher construct stiffness and lower plate strain than the long working length. Load sharing due to transcortical contact observed in our model in tension bending will vary with fracture gap, working length, and loading condition. These results must be interpreted with caution when considering clinical relevance or potential in vivo biomechanical advantages., Competing Interests: None declared., (Thieme. All rights reserved.)

Summary: Preoperative computed tomographic angiography is increasingly performed before perforator flap-based reconstruction. However, radiologic two-dimensional thin slices do not allow for intuitive interpretation and translation to intraoperative findings. Three-dimensional volume rendering has been used to alleviate the need for mental two-dimensional to three-dimensional abstraction. Even though volume rendering allows for a much easier understanding of anatomy, it currently has limited utility, as the skin obstructs the view of critical structures. Using free, open-source software, the authors introduce a new skin-masking technique that allows surgeons to easily create a segmentation mask of the skin that can later be used to toggle the skin on and off. In addition, the mask can be used in other rendering applications. The authors use Cinematic Anatomy for photorealistic volume rendering and interactive exploration of computed tomographic angiography with and without skin. The authors present results from using this technique to investigate perforator anatomy in deep inferior epigastric perforator flaps and demonstrate that the skin-masking workflow is performed in less than 5 minutes. In Cinematic Anatomy, the view onto the abdominal wall and especially onto perforators becomes significantly sharper and more detailed when no longer obstructed by the skin. The authors perform a virtual, partial muscle dissection to show the intramuscular and submuscular course of the perforators. The skin-masking workflow allows surgeons to improve arterial and perforator detail in volume renderings easily and quickly by removing skin and could alternatively be performed solely using open-source and free software. The workflow can be easily expanded to other perforator flaps without the need for modification., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Plastic surgeons routinely use 3D-models in their clinical practice, from 3D-photography and surface imaging to 3D-segmentations from radiological scans. However, these models continue to be viewed on flattened 2D screens that do not enable an intuitive understanding of 3D-relationships and cause challenges regarding collaboration with colleagues. The Metaverse has been proposed as a new age of applications building on modern Mixed Reality headset technology that allows remote collaboration on virtual 3D-models in a shared physical-virtual space in real-time. We demonstrate the first use of the Metaverse in the context of reconstructive surgery, focusing on preoperative planning discussions and trainee education. Using a HoloLens headset with the Microsoft Mesh application, we performed planning sessions for 4 DIEP-flaps in our reconstructive metaverse on virtual patient-models segmented from routine CT angiography. In these sessions, surgeons discuss perforator anatomy and perforator selection strategies whilst comprehensively assessing the respective models. We demonstrate the workflow for a one-on-one interaction between an attending surgeon and a trainee in a video featuring both viewpoints as seen through the headset. We believe the Metaverse will provide novel opportunities to use the 3D-models that are already created in everyday plastic surgery practice in a more collaborative, immersive, accessible, and educational manner., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F. Necker is a part-time research student at Siemens Healthineers (Erlangen, Germany). Dr. C.W. Leuze is a co-founder and owner of Nakamir Inc (Menlo Park, CA). Dr. A. Momeni is a consultant for AxoGen, Gore, RTI, and Sientra. The remaining authors have no conflict of interest to disclose.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing., (© 2024. The Author(s).)

Objective:  To evaluate the effect of 3.5-mm locking compression plate (LCP) length on construct stiffness and plate and bone model strain in a synthetic, short-fragment, fracture-gap model., Study Design:  Six replicates of 6-hole, 8-hole, 10-hole, and 12-hole LCP constructs on a short-fragment, tubular Delrin fracture gap model underwent four-point compression and tension bending. Construct stiffness and surface strain, calculated using three-dimensional digital image correlation, were compared across plate length and region of interest (ROI) on the construct., Results:  The 12-hole plates (80% plate-bone ratio) had significantly higher construct stiffness than 6-hole, 8-hole, and 10-hole plates and significantly lower plate strain than 6-hole plates at all ROIs. Strain on the bone model was significantly lower in constructs with 10-hole and 12-hole plates than 6-hole plates under both compression and tension bending., Conclusion:  Incremental increases in construct stiffness and incremental decreases in plate strain were only identified when comparing 6-hole, 8-hole, and 10-hole plates to 12-hole plates, and 6-hole to 12-hole plates, respectively. Strain on the bone model showed an incremental decrease when comparing 6-hole to 10-hole and 12-hole plates. A long plate offered biomechanical advantages of increased construct stiffness and reduced plate and bone model strain, over a short plate in this in vitro model., Competing Interests: None declared., (Thieme. All rights reserved.)