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Abstract Background Vegan diets have recently gained popularity in Switzerland as well as globally. The aim of the present study was to develop a diet quality score for vegans (DQS-V) based on the Swiss dietary recommendations for vegans. Methods The dataset included 52 healthy vegan adults. Dietary intake data were assessed by three-day weighed food records. Body weight and height were measured, and a venous blood sample for the analysis of vitamin and mineral status was collected. Spearman rank correlation coefficients were used due to not-normally distributed data. Dietary patterns were identified using principal component analysis (PCA). Results The DQS-V score (mean ± SD) was 48.9 ± 14.7. Most vegans adhered to the recommended portions of vegetables, vitamin C-rich vegetables, fruits, omega-3-rich nuts, fats and oils, and iodized salt. However, the intake of green leafy vegetables, vitamin C-rich fruits, wholegrains, legumes, nuts and seeds, selenium-rich nuts, zero caloric liquid, and calcium-fortified foods was suboptimal. The sample overconsumed sweet-, salty-, fried foods, and alcohol. The DQS-V had a significantly positive correlation with intakes of fibre, polyunsaturated fatty acids, potassium, zinc, and phosphorus intakes (p’s

Human induced pluripotent stem cell (hiPSC) line INEUi001-A was reprogrammed from peripheral blood mononuclear cells (PBMC) using the lentiviral-hSTEMCCA-loxP vector. PBMCs were obtained from a 75- year-old female ALS/FTD disease patient carrying a heterozygous deletion within the C9ORF72 hexanucleotide repeat region resulting in a GGGGCCG sequence (∼1.16 repeats). C9ORF72 genotype was maintained and stemness and pluripotency confirmed in INEUi001-A hiPSC line.

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training’s effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

Abstract Background CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. Results We found that CBPKIX/KIX mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBPKIX/KIX mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBPKIX/KIX mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. Conclusions These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms. Graphical abstract

Rose Bengal (RB) is a xanthene dye used as a sensitizer to convert triplet (3O2) to singlet oxygen (1O2). This photophysical property makes it one of the most used dyes in photodynamic therapy. Thus, understanding its interaction with biomacromolecules can provide helpful information about its mode of action and application. The protein chosen for this study was human serum albumin (HSA), which has nine binding sites for fatty acids (FA), and at least three sites for interactions of drugs (DS). The complexation of HSA with RB caused a maximum bathochromic shift in its absorption. From this displacement and the application of the Benesi–Hildebrand model, the ligand–protein association constant (3.90 ± 0.08 × 105 M−1) was obtained. Applying the Job’s Plot method resulted in a 6:1 (ligand-protein) stoichiometry. The determination of preferred binding sites was performed by measuring the association constant in the presence of drugs for which their binding sites in HSA are already well established, such as warfarin (DS1), ibuprofen (DS2 and FA6), digitoxin (DS3), diazepam (DS2), and diflunisal (DS2 and FA6). From these studies, it was found that RB is able to bind at DS1, DS3, and FA6 sites but not at DS2. Subsequently, molecular docking studies using the 2BX8 and 2BXE crystallographic structures were performed and corroborated the experimental results. The lowest energy poses were −52.13, −58.79, and −67.55 kcal mol−1 at DS1, DS3, and FA6, respectively. Conversely, DS2 was the lower affinity binding site. In conclusion, HSA has a high affinity for RB, being able to bind up to six dye molecules.

Abstract The aim of this study was to investigate the effects of yerba mate (Ilex paraguariensis St. Hil.) extract (YME) on oxidative stress parameters and pathological changes in the lungs of mice chronically exposed to hand-rolled cornhusk cigarette (HRC) smoke. Twenty-four male Swiss mice were divided into four groups exposed to the following treatments: control (ambient air), HRC, YME, and HRC plus YME. The animals were exposed to four HRCs per session, with 3 sessions/day, every day for 30 days. Twenty-four hours after the last inhalation, the mice were killed, and the left lungs were removed. The results showed that HRC contains elevated levels of tin and carbon oxide, but less arsenic, cobalt, manganese, and selenium than commercial cigarettes. YME administration reversed fibrosis, alveolar enlargement, and hemorrhage induced by HRC smoke. In addition, the YME and HRC significantly reduced the production of oxidants, oxidative damage and promoted a significant increase in total thiol. In conclusion, exposure to HRC smoke compromised pulmonary histoarchitecture by promoting structural changes and increasing oxidative stress in tissues. However, concomitant treatment with YME regulated the redox state and reduced the harmful effects of HRC smoke exposure in the lungs.

The aim of this study was to identify, by magnetic resonance imaging (MRI), the ability of the blood-pool contrast agent B22956/1 to detect atherosclerotic plaques developing at the brachiocephalic artery of apolipoprotein E knockout (apoE-KO) mice and to possibly identify vulnerable atherosclerotic lesions. After high-fat feeding for 8 or 12 weeks, MRIs of brachiocephalic arteries were acquired before and after B22956/1 administration; then vessels were removed and analyzed by histology. B22956/1 injection caused a rapid increase in plaque signal enhancement and plaque to muscle contrast values, which remained stable up to 70 minutes. A linear correlation between signal enhancement and macrophage content was found 10 minutes after B22956/1 injection ( p < .01). Signal enhancement and plaque to muscle contrast values correlated with macrophage content 40 minutes after contrast agent administration ( p < .01). Finally, 70 minutes after B22956/1 infusion, plaque to muscle contrast significantly correlated with the percentage of stenosis ( p < .005). B22956/1 administration to high fat-fed apoE-KO mice resulted in a rapid enhancement of atherosclerotic plaques and in a great ability to rapidly visualize vulnerable plaques, characterized by a high macrophage content. These results suggest that B22956/1 could represent an interesting tool for the identification of atherosclerotic plaques potentially leading to acute cardiovascular events.

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E(-/-) mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE(-/)- mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20:4n-6) and oleic acid (C18:1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE(-/-) mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids.

Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs) and proliferation of mitochondria. This study aimed to penetrate the effect of TTA on the development of atherosclerotic lesions in apolipoprotein (apo)-E(-/-) mice fed a high-fat diet containing 0.3% TTA for 12 weeks. These mice displayed a significantly less atherosclerotic development vs control. Plasma cholesterol was increased by TTA administration and triacylglycerol (TAG) levels in plasma and liver were decreased by TTA supplementation, the latter, probably due to increased mitochondrial fatty acid oxidation and reduced lipogenesis. TTA administration also changed the fatty acid composition in the heart, and the amount of arachidonic acid (ARA) and eicosapentaenoic acid (EPA) was reduced and increased, respectively. The heart mRNA expression of inducible nitric oxidase (NOS)-2 was decreased in TTA-treated mice, whereas the mRNA level of catalase was increased. Finally, reduced plasma levels of inflammatory mediators as IL-1α, IL-6, IL-17, TNF-α and IFN-γ were detected in TTA-treated mice. These data show that TTA reduces atherosclerosis in apoE(-/-) mice and modulates risk factors related to atherosclerotic disorders. TTA probably acts at both systemic and vascular levels in a manner independent of changes in plasma cholesterol, and triggers TAG catabolism through improved mitochondrial function.

Introduction/Aims: Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. Methods: One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy. Results: Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12–322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17–416.43) in psoriasis patients and 18.75 (95% CI = 1.07–327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length‐dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p =.0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant. Discussion: Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Resumo Este estudo teve por objetivo comparar os efeitos do exercício agudo com carga de trabalho relativa em gastrocnêmio de ratos Wistar com três e 18 meses. Os animais foram divididos em quatro grupos (n = 6): controle de três e 18 meses; exercício de três e 18 meses. Os grupos exercitados foram submetidos a uma única sessão de corrida na esteira com 60 minutos em velocidade de 0,8 km/h e 1,2 km/h. Foram analisados parâmetros do metabolismo (níveis de lactato, conteúdo de glicogênio, níveis de succinato desidrogenase, citocromo c oxidase e de estresse oxidativo (SOD, CAT e GPX). Os resultados mostraram um aumento nos marcadores metabólicos após o exercício agudo independentemente da idade dos animais e similaridade nos danos oxidativos apesar de as enzimas antioxidantes apresentarem modulação diferenciada nos animais mais velhos em comparação com animais jovens.

Background Studies have demonstrated an inverse relationship between body mass index (BMI) and the risk of developing lung cancer. We conducted a retrospective cohort study evaluating baseline quantitative computed tomography (CT) measurements of body composition, specifically muscle and fat area in a large CT lung screening cohort (CTLS). We hypothesized that quantitative measurements of baseline body composition may aid in risk stratification for lung cancer. Methods Patients who underwent baseline CTLS between January 1st, 2012 and September 30th, 2014 and who had an in-network primary care physician were included. All patients met NCCN Guidelines eligibility criteria for CTLS. Quantitative measurements of pectoralis muscle area (PMA) and subcutaneous fat area (SFA) were performed on a single axial slice of the CT above the aortic arch with the Chest Imaging Platform Workstation software. Cox multivariable proportional hazards model for cancer was adjusted for variables with a univariate p < 0.2. Data were dichotomized by sex and then combined to account for baseline differences between sexes. Results One thousand six hundred and ninety six patients were included in this study. A total of 79 (4.7%) patients developed lung cancer. There was an association between the 25th percentile of PMA and the development of lung cancer [HR 1.71 (1.07, 2.75), p < 0.025] after adjusting for age, BMI, qualitative emphysema, qualitative coronary artery calcification, and baseline Lung-RADS® score. Conclusions Quantitative assessment of PMA on baseline CTLS was associated with the development of lung cancer. Quantitative PMA has the potential to be incorporated as a variable in future lung cancer risk models., Author(s): Lee Gazourian [sup.1], Chantal S. Durgana [sup.2], Devon Huntley [sup.3], Giulia S. Rizzo [sup.4], William B. Thedinger [sup.3], Shawn M. Regis [sup.5], Lori Lyn Price [sup.6] [sup.7], Elizabeth J. [...]

OBJECTIVES: Progressive decline of physiological processes with aging is normal. Aging is also associated with decreased functional capacity and onset of many diseases. This study evaluated the changes in physical fitness (PF), body composition (BC), and lipid profile (LP) in elderly men completing different training protocols. METHODS: Fifty-five men (age 60-80 years) were randomized into the following groups: without training, aerobic training on dry land, combined training on dry land, and combined training in water. Training was conducted for 8 weeks, and PF, LP, and BC were assessed at the beginning and end of the intervention. RESULTS: Significant improvements were observed in all parameters; however, combined programs on land or in water were more effective at improving strength and aerobic fitness. Combined exercise produced greater effects on BC and LP and some muscle fitness parameters; however, improvements in muscular and aerobic capacities occurred independently of exercise type or model. CONCLUSION: These results indicate that the effects of training occur regardless of training type or model, and are directly associated with training periodization, adherence, and regularity.

Purpose: Pseudoaneurysm (PA) of the access artery is a common and potentially severe complication after percutaneous endovascular interventions. Most PA require interventional therapy, including thrombin injection, covered stent implantation, or surgical repair, which are costly and associated with other complications. Treating PA by external compression is uncomfortable and time consuming, with a low success rate. By injecting local tumescence anesthesia around the PA and close to its neck, the tumescence anesthesia and echo-guided compression technique (TACT) aims to improve efficacy and patient's comfort. Materials and Methods: We retrospectively reviewed all consecutive patients treated for femoral PA in our center from May 2009 to July 2019 and estimated efficacy and safety. Vascular specialists performed TACT according to a standardized protocol including ultrasound-guided injection of tumescence solution (45 ml of 0.9% saline, 15 ml of lidocaine 1%/epinephrine 5 μg/ml) in the soft tissue around the PA and its neck, local compression with the sonography probe until PA closure, and external compression by elastic belt for 3 hours. Results: Among a total of 125 patients with femoral artery PA, 82 (65.6%) were treated by TACT (including 3 patients with haemorrhagic shock), 14 (11.2%) by thrombin injection; 12 (9.6%) by endovascular interventions; 8 (6.4%) by open surgery; and 9 (7.2%) conservatively. In patients treated by TACT, PA neck was short (<1 cm) in 51.8% and mean cavity diameter 30 ± 23 mm. After injection of 58 ± 8 ml of tumescence solution, mean time of echo-guided compression was 12 ± 8 minutes. Pseudoaneurysm was successfully closed in 92.7% after the first attempt and in 96.3% after the second attempt. The intervention was well tolerated, without any adverse event. Conclusion: Tumescence anesthesia and echo-guided compression technique (TACT) is an effective and safe treatment for PA. Compared to other therapies, TACT is minimally invasive and widely available for minimal costs, even for large PA and in unstable patients. Clinical Impact: Tumescence anesthesia and echo-guided compression technique seems to be an efficient, safe, and a fair economical choice in comparison with alternative techniques. The implementation of this procedure is simple with low risk of complications. Based on the results of this study, we believe that TACT should be considered as the first-line treatment of most iatrogenic PA. [ABSTRACT FROM AUTHOR]