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In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Veliparib Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals.Mitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the absence of a specific disease-modifying therapy. Management of patients with MDs is based on different therapeutical strategies, particularly the early treatment of organ-specific complications and the avoidance of catabolic stressors or toxic medication. In this review, we discuss the therapeutic management of MDs, supported by a revision of the literature, and provide an overview of the drugs that should be either avoided or carefully used both for the specific treatment of MDs and for the management of comorbidities these subjects may manifest. We finally discuss the latest therapies approved for the management of MDs and some ongoing clinical trials.Surgery, including minimally invasive surgery, and radiotherapy are key modalities in the treatment of gynecological malignancies. The aim of this review is to offer the multidisciplinary care team a comprehensive summary of the intersections of surgery and radiotherapy in the local treatment of gynecological malignancies. Recent advances in radiotherapy are highlighted. Relevant publications were identified through a review of the published literature. Ovarian, endometrial, cervical, vaginal, and vulvar cancer were included in the search. Current guidelines are summarized. The role of radiotherapy in adjuvant as well as definitive treatment of these entities is synthesized and put into context with surgery, focusing on survival and quality of life. link2 Although these outcomes have improved recently, further research must be focused on the number of life years lost, and the potential morbidity encountered by patients.CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5237 proteins, of which significant alterations in the levels of 1119 proteins were observed between resting and activated CD4+ T cells. In addition to identifying several known T-cell activation-related processes altered expression of several stimulatory/inhibitory immune checkpoint markers between resting and activated CD4+ T cells were observed. Network analysis further revealed several known and novel regulatory hubs of CD4+ T cell activation, including IFNG, IRF1, FOXP3, AURKA, and RIOK2. Comparison of primary CD4+ T cell proteomic profiles with human lymphoblastic cell lines revealed a substantial overlap, while comparison with mouse CD+ T cell data suggested interspecies proteomic differences. The current dataset will serve as a valuable resource to the scientific community to compare and analyze the CD4+ proteome.Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with relatively much less attention given to other body systems, such as the gastrointestinal tract and its particular connection with the brain, known as the brain-gut axis. This narrative review provides an overview of the effect of coffee brew; its by-products; and its components on the gastrointestinal mucosa (mainly involved in permeability, secretion, and proliferation), the neural and non-neural components of the gut wall responsible for its motor function, and the brain-gut axis. Despite in vitro, in vivo, and epidemiological studies having shown that coffee may exert multiple effects on the digestive tract, including antioxidant, anti-inflammatory, and antiproliferative effects on the mucosa, and pro-motility effects on the external muscle layers, much is still surprisingly unknown. link3 Further studies are needed to understand the mechanisms of action of certain health-promoting properties of coffee on the gastrointestinal tract and to transfer this knowledge to the industry to develop functional foods to improve the gastrointestinal and brain-gut axis health.

The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in ≥80 years patients.

From June 1998 to July 2017, 101 patients ≥80 years were included in a tertiary center. link= Veliparib The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A;

= 41) and 15 months for HR prostate cancer (group B;

= 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity.

Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of ≥80 years patients with no impact on OS. In the multivariate analysis, age <82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS.

Age ≥80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.

Age ≥80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.Mucositis is a common side-effect of chemotherapy treatment, inducing alterations in the composition of the gut microbiota. Redox active compounds, such as vitamins B2 and C, have been shown to reduce inflammation and enhance the growth of anaerobic bacteria in the gut. We therefore aimed to (1) validate the ability of these compounds to promote bacterial cell growth in vitro, and (2) determine their prophylactic efficacy in a rat model of methotrexate (MTX)-induced mucositis. link2 Bacterial growth curves were performed to assess the growth kinetics of bacteria exposed to Vitamins C and B2 (0.5 mM). Male wistar rats (150-200 g) received vitamins B2 (12 mg/day) and C (50 mg/day) via daily oral gavage (from day -1 to day 10). MTX (45 mg/Kg) was administrated via I.V. injection (N = 4-8/group) on day 0. Body weight, water/food consumption and diarrhea were assessed daily. Blood and faecal samples were collected longitudinally to assess citrulline levels (mucositis biomarker) and gut microbiota composition. Vitamins C/B2 enhanced the in vitro growth of anaerobic bacteria Blautia coccoides and Roseburia intestinalis. Contrarily to vitamin B2, in vivo administration of Vitamin C significantly attenuated clinical symptoms of mucositis. Despite their influence on the composition of the gut microbiota, both vitamins did not modulate the course of MTX-induced mucositis, as accessed by plasma citrulline. Vitamins B2 and C enhanced anaerobic bacterial growth in vitro, however their ability to mitigate MTX-induced mucositis was limited.Carukia barnesi was the first in an expanding list of cubozoan jellyfish whose sting was identified as causing Irukandji syndrome. Nematocysts present on both the bell and tentacles are known to produce localised stings, though their individual roles in Irukandji syndrome have remained speculative. This research examines differences through venom profiling and pulse wave Doppler in a murine model. The latter demonstrates marked measurable differences in cardiac parameters. Veliparib The venom from tentacles (CBVt) resulted in cardiac decompensation and death in all mice at a mean of 40 min (95% CL ± 11 min), whereas the venom from the bell (CBVb) did not produce any cardiac dysfunction nor death in mice at 60 min post-exposure. This difference is pronounced, and we propose that bell exposure is unlikely to be causative in severe Irukandji syndrome. To date, all previously published cubozoan venom research utilised parenterally administered venom in their animal models, with many acknowledging their questionable applicability to real-world envenomation. Our model used live cubozoans on anaesthetised mice to simulate normal envenomation mechanics and actual expressed venoms. Consequently, we provide validity to the parenteral methodology used by previous cubozoan venom research.Long-term enteral nutrition (LTEN) can induce gut microbiota (GM) dysbiosis and gastrointestinal related symptoms, such as constipation or diarrhoea. To date, the treatment of constipation is based on the use of laxatives and prebiotics. Only recently have probiotics and synbiotics been considered, the latter modulating the GM and regulating intestinal functions. This randomized open-label intervention study evaluated the effects of synbiotic treatment on the GM profile, its functional activity and on intestinal functions in long-term home EN (LTHEN) patients. Twenty LTHEN patients were recruited to take enteral formula plus one sachet/day of synbiotic (intervention group, IG) or enteral formula (control group, CG) for four months and evaluated for constipation, stool consistency, and GM and metabolite profiles. In IG patients, statistically significant reduction of constipation and increase of stool consistency were observed after four months (T1), compared to CG subjects. GM ecology analyses revealed a decrease in the microbial diversity of both IC and CG groups. Biodiversity increased at T1 for 5/11 IG patients and Methanobrevibacter was identified as the biomarker correlated to the richness increase. Moreover, the increase of short chain fatty acids and the reduction of harmful molecules have been correlated to synbiotic administration. Synbiotics improve constipation symptoms and influences Methanobrevibacter growth in LTHEN patients.The triglyceride glucose (TyG) index, a product of triglyceride and fasting glucose, is a reliable marker for insulin resistance. We aimed to investigate the association between the TyG-related markers and coronary artery calcification (CAC) progression. We enrolled 1145 asymptomatic participants who underwent repeated CAC score measurements during routine health examinations. Homeostasis model assessment of insulin resistance (HOMA-IR), TyG index, TyG-BMI (body mass index), and TyG-WC (waist circumference) were calculated. link3 Progression of CAC was defined as (1) incident CAC in a CAC-free population, or an (2) increase of ≥2.5 units between the baseline and final square root of the CAC scores in participants with detectable CAC. According to the quartiles of parameters, we stratified the subjects into four groups. The prevalence of progression increased with the TyG-WC quartile (15.0%, 24.1%, 31.0%, and 32.2% for each of the groups; p less then 0.001). The multivariate-adjusted odds ratio (95% confidence interval) for CAC score progression was 1.

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