Lamontroy2059

Disrupted cognition and chronic musculoskeletal pain (CMP) are prevalent experiences among Gulf War Veterans (GWV). A negative association between CMP and cognition (i.e., chronic pain-related cognitive interference) has been observed in some chronic pain populations but has not been evaluated in GWV. Additional research suggests that disrupted cognition in GWV with CMP may be exacerbated by stressing the nociceptive system. Therefore, we compared cognitive performance and related neural activity between CMP and healthy control (CO) GWV in the absence and presence of experimental pain.

During functional magnetic resonance imaging (fMRI), Veterans (CMP=29; CO=27) completed cognitive testing via congruent and incongruent conditions of a modified Stroop task (Stroop-only). A random subset (CMP=13; CO=13) also completed cognitive testing with experimental pain (Pain+Stroop). Yuen's modified t-test and robust mixed-model analysis of variance (ANOVA) models were used for analyzing cognitive performance data. Independent t-tests and repeated-measures ANOVA models were employed for fMRI data with thresholding for multiple-comparisons (p<0.005) and cluster size (> 320mm

).

Functional MRI analysis revealed significant between-group differences for the incongruent but not congruent-Stroop run. Neither correct responses nor reaction time differed between groups in either Stroop condition (all p≥0.21). Significant group (CMP, CO) by run (Stroop-only, Pain+Stroop) interactions revealed greater neural responses in CMP Veterans during Pain+Stroop runs. No significant interactions were observed for correct responses or reaction time (p≥0.31).

GWV with CMP require a greater amount of neural resources to sustain cognitive performance during nociceptive stress.

GWV with CMP require a greater amount of neural resources to sustain cognitive performance during nociceptive stress.Intestinal inflammation is associated with the integrity of the intestinal epithelium, which forms a physical barrier against noxious luminal substances. Heat shock 70 kDa protein 1A (HSP70), a molecular chaperon that exerts a cytoprotective effect, regulates intestinal integrity. This study investigated the modulation of HSP70 expression by dietary polyphenols, with particular reference to curcumin, in human intestinal Caco-2 cells. Immunoblot analysis demonstrated that among the 21 different polyphenols tested, curcumin most potently increased HSP70 levels in Caco-2 cells without affecting cell viability. Curcumin also increased the phosphorylation of heat shock factor 1 (HSF1), a well-known transcription factor of HSP70. Promoter and qRT-PCR assays indicated that curcumin upregulated Hspa1a levels via transcriptional activation. Pharmacological inhibition of MEK, a mechanistic target of rapamycin, p38 mitogen-activated protein kinase, and phosphatidyl 3-inositol kinase suppressed curcumin-mediated HSP70 expression, whereas HSF1 phosphorylation was sensitive only to MEK inhibition. Taken together, curcumin increases the expression of HSP70 in intestinal Caco-2 cells via transcriptional activation, possibly enhancing cell integrity. The effects exerted by curcumin are regulated by various signaling pathways. Our findings will expectedly contribute to a deeper understanding of the regulation of intestinal HSP70 by dietary components.The basophils, first described by Paul Ehlrich in 1879, are rare circulating cells, representing approximately 0.01 to 0.3% of the blood leukocytes. Until recently, these cells have been neglected because of their minority status among immune cells and because they show some similarities to mast cells residing in tissues. However, basophils and mast cells are now recognized as distinct cell lines and it appears that basophils have important and non-redundant functions, distinct from those of mast cells. On the one hand, basophils have beneficial contribution to protective immunity, in particular against parasitic infections. On the other hand, basophils are involved in the development of various benign and malignant pathologies, ranging from allergy to certain leukemias. Basophils interact with other immune cells or neoplastic cells through direct contacts or soluble mediators, such as cytokines and proteases, thus contributing to the regulation of the immune system but also to allergic responses, and probably to the process of neoplastic transformation. In this review, we will develop recent knowledge on the involvement of basophils in the modulation of innate and adaptive immunity. We will then describe the benign or malignant circumstances in which an elevation of circulating basophils can be observed. Finally, we will discuss the role played by these cells in the pathophysiology of certain leukemias, particularly during chronic myeloid leukemia.

To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG).

One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe.

Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy.

Patients were randomized 31 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive mitomycin C (0.2 mg/ml for 2 minutes).

The primary effectiveness end point was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness end points at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional end points included glaucoma medication use .01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients.

Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.

Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.Phytoestrogens have been identified as a natural, plant-based alternative to synthetically derived estrogens, to supplement the absence of endogenous estrogens in post-menopausal women, and attenuate the progression of pathologies and side-effects associated with menopause. The increased availability of these plant's derived compounds as diet or nutritional supplements makes their ingestion and consumption easier and more accessible as compared to pharmacological alternatives. Further, phytoestrogen intake has shown beneficial effects as estrogens alternatives in attenuating severe complications in diseases such as type 2 diabetes, metabolic syndrome, NAFLD, and obesity. However, in many cases phytoestrogen effectiveness remains largely circumstantial or just anecdotal as significant uncertainties on the relative abundance of different phytoestrogens in a given diet, the need for conversion to an active principle through the gut microbiome, the possibility of an effect threshold, the synergistic effect of different phytoestrogens possible due to different modality of actions still persist. The present article aims at highlighting the main issues and concerns plaguing the field as well as some of the possible causes of inconsistencies observed in the various nutritional and clinical studies attempted so far.Decontamination of unprotected skin areas is crucial to prevent excessive penetration of chemical contaminants after criminal or accidental release. A review of literature studies was performed to identify the available decontamination methods adopted to treat skin contamination after chemical, radiological and metal exposures. In this bibliographic review, an overview of the old and recent works on decontamination procedures followed in case of potential hazards substances contaminations with a comparison between these systems are provided. Almost all data from our 95 selected studies conducted in vitro and in vivo revealed that a rapid skin decontamination process is the most efficient way to reduce the risk of intoxication. The commonly-used or recommended conventional procedures are simple rinsing with water only or soapy water. However, this approach has some limitations because an easy removal by flushing may not be sufficient to decontaminate all chemical deposited on the skin, and skin absorption can be enhanced by the wash-in effect. Other liquid solutions or systems as adsorbent powders, mobilizing agents, chelation therapy are also applied as decontaminants, but till nowadays does not exist a decontamination method which can be adopted in all situations. Therefore, there is an urgent need to develop more efficient and successful decontaminating formulations.Imatinib, a specific Bcr-Abl tyrosine kinase inhibitor, is the most commonly used drug in the treatment of chronic myeloid leukemia. However, optimal response is not achieved in up to 33% of patients. Therefore, development of novel therapeutic strategies for chronic myeloid leukemia is critical. Betulinic (1) and ursolic (2) acids are natural pentacyclic triterpenes that exhibit antileukemic activities. In this study, we evaluated the effects of pharmacomodulations at the C-3 position of the triterpene moiety of betulinic and ursolic acids on their activity against K562 leukemia cells. Six new derivatives (1a-2c) were synthesized and evaluated for pro-apoptotic and anti-proliferative effects in mammalian and leukemic cells. 2c derivative containing an amine group at the C-3 position of ursolic acid was the most active against leukemia cells with an IC50 value of 5.2 μM after 48 h of treatment. 2c did not exhibit cytotoxic effects against VERO and HepG2 cells and human lymphocytes, showing a good selectivity index for cancer over normal cells. Induced cell death by apoptosis via caspases 3 and 8, and also caused cell cycle arrest as evidenced by accumulation of cells in the G1 phase and decreased cell population in the G2 phase. Furthermore, co-treatment of 2c with imatinib, the chemotherapy drug most commonly used to treat leukemia, resulted in a synergistic effect. Our findings provide a strong rationale for further investigation of combination therapy using the 2c derivative and imatinib in pre-clinical studies.In recent years, various AI-based methods have been developed in order to uncover chemico-biological interactions associated with DNA damage and oxidative stress. Various decision trees, bayesian networks, random forests, logistic regression models, support vector machines as well as deep learning tools, have great potential in the area of molecular biology and toxicology, and it is estimated that in the future, they will greatly contribute to our understanding of molecular and cellular mechanisms associated with DNA damage and repair. Selleckchem GSK3 inhibitor In this concise review, we discuss recent attempts to build machine learning tools for assessment of radiation - induced DNA damage as well as algorithms that can analyze the data from the most frequently used DNA damage assays in molecular biology. We also review recent works on the detection of antioxidant proteins with machine learning, and the use of AI-related methods for prediction and evaluation of noncoding DNA sequences. Finally, we discuss previously published research on the potential application of machine learning tools in aging research.