Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure.

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc–modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease

Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation

Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring

Compositional and diversity comparisons between the palynological records of the Neogene (Solimões Formation) and Holocene sediments of Western Amazonia

Western Amazonia underwent dramatic changes in its landscape and environments during the Neogene, which led to its extant, hyperdiverse, tropical rainforest. Although the palynological fossil record has been the most useful proxy for understanding the history of the Amazonian biome, the floristic composition and diversity of the Neogene and the present Amazonian environments have never been thoroughly compared. In this work, we present preliminary comparisons of the pollen content of a Miocene core from the Solimões Formation in western Amazonia (Brazil) with the pollen content of Holocene sediments from flooded environments (várzeas and lake margins) near the Miocene site. We found a total of 463 pollen and spore types (Miocene, n = 284; Holocene, n = 231), only 52 of which were shared. The Holocene flooding environments displayed distinct palynological signals; both the Holocene and Miocene palynofloras have pollen primarily sourced from the local, flooded environments, with no significant differences in within-sample pollen diversity. The Holocene palynoflora was more heterogeneous in composition than the Miocene palynoflora, probably because the Miocene wetlands (the Pebas System) were highly homogeneous at a continental scale, far more than modern western Amazonia, thus implying that the spatial vegetation turnover was much lower than in modern ecosystems. © 2019, © 2019 AASP–The Palynological Society

Sex and Gender-Related Differences in the Outcome of Total Hip Arthroplasty: A Current Concepts Review

Background and Objectives: Sex and gender-related differences may influence the outcome of patients undergoing total hip arthroplasty (THA). The present paper aims to depict the importance of sex and gender-related issues in the perioperative management of patients undergoing THA to improve clinical outcomes and prevent postoperative complications. Materials and Methods: From January 2002 to August 2022, OVID-MEDLINE, EMBASE, SCOPU S, Web of Science, Google Scholar, and PubMed were searched to identify relevant studies for further analysis. The search strategy included the following terms: ((“gender-related differences” [MeSH Terms] OR “sex-related differences” [All Fields]) OR (“gender indicators” [MeSH Terms] OR “sex” [All Fields])) AND (“total hip arthroplasty” [MeSH Terms] OR (total hip replacement [All Fields])). Results: Twenty-eight papers were included in this current concepts review. Sex and gender-related differences were analyzed with regard to the following points: (1) surgical approach, robotic surgery, scar cosmesis, and implant choice; (2) postoperative clinical outcome and complications; (3) sexual activity after THA; and (4) psychological status and daily functional requirements. The data analysis showed that female patients need more specific attention in the preoperative, intraoperative, and postoperative phases to improve clinical and functional outcomes, reduce complications risk, and manage patient satisfaction. Conclusions: THA outcomes may be influenced by sex and gender-related factors which should be carefully assessed and addressed in patients undergoing surgery to improve the postoperative outcomes of patients’ satisfaction and reduce postoperative complications that can differ between the two sexes

Ancient Grain Flours with Different Degrees of Sifting: Advances in Knowledge of Nutritional, Technological, and Microbiological Aspects

Ancient grains have gained considerable attention in recent years, as some research suggests they may be healthier than modern wheat. The present study aims to evaluate the chemical, rheological, and microbiological features of three Southern Italian cultivated ancient wheat varieties: Risciola, Carosella, and Saragolla. ATR-FTIR analyses were performed on the finely ground grain samples of the three varieties. The selected grains were ground with a stone mill, and different sifting degrees (whole—100%, type 1—80%, and type 0—72%) were evaluated. The flours showed a good nutritional profile, a higher amylose/amylopectin ratio, and a lower glycemic index than the literature. The gluten index of the samples was in the range 2.6–28.9%, and the flours can be classified as weak, having a value <30%. The farinographic test showed a short development time, low dough stability, a high softening degree, and water absorption, which increased with the degree of sifting. Microbiological analyses performed on flours from ancient grains at different degrees of sifting show their safety, according to their microbiological parameters, which fall within the legal microbiological requirements established by the European Commission Regulation (EC)

A Novel DLG1 Variant in a Family with Brugada Syndrome: Clinical Characteristics and In Silico Analysis

Background: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated to sudden cardiac death. Overall, variants have been identified in eighteen genes encoding for ion channel subunits and seven genes for regulatory proteins. Recently, a missense variant in DLG1 has been found within a BrS phenotype-positive patient. DLG1 encodes for synapse associated protein 97 (SAP97), a protein characterized by the presence of multiple domains for protein–protein interactions including PDZ domains. In cardiomyocytes, SAP97 interacts with Nav1.5, a PDZ binding motif of SCN5A and others potassium channel subunits. Aim of the Study: To characterize the phenotype of an Italian family with BrS syndrome carrying a DLG1 variant. Methods: Clinical and genetic investigations were performed. Genetic testing was performed with whole-exome sequencing (WES) using the Illumina platform. According to the standard protocol, a variant found by WES was confirmed in all members of the family by bi-directional capillary Sanger resequencing. The effect of the variant was investigated by using in silico prediction of pathogenicity. Results: The index case was a 74-year-old man with spontaneous type 1 BrS ECG pattern that experienced syncope and underwent ICD implantation. WES of the index case, performed assuming a dominant mode of inheritance, identified a heterozygous variant, c.1556G>A (p.R519H), in the exon 15 of the DLG1 gene. In the pedigree investigation, 6 out of 12 family members had the variant. Carriers of the gene variant all had BrS ECG type 1 drug induced and showed heterogeneous cardiac phenotypes with two patients experiencing syncope during exercise and fever, respectively. The amino acid residue #519 lies near a PDZ domain and in silico analysis suggested a causal role for the variant. Modelling of the resulting protein structure predicted that the variant disrupts an H-bond and a likelihood of being pathogenic. As a consequence, it is likely that a conformational change affects protein functionality and the modulating role on ion channels. Conclusions: A DLG1 gene variant identified was associated with BrS. The variant could modify the formation of multichannel protein complexes, affecting ion channels to specific compartments in cardiomyocytes