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During cellular stress it is essential for cells to alter their gene expression to adapt and survive. Gene expression is regulated at multiple levels, but translation regulation is both a method for rapid changes to the proteome and, as one of the most energy-intensive cellular processes, a way to efficiently redirect cellular resources during stress conditions. Despite this ideal positioning, many of the specifics of how translation is regulated, positively or negatively, during various types of cellular stress remain poorly understood. To further assess this regulation, we examined the essential translation factor Ded1, an RNA helicase that has been previously shown to play important roles in the translational response to cellular stress. In particular, ded1 mutants display an increased resistance to growth inhibition and translation repression induced by the TOR pathway inhibitor, rapamycin, suggesting that normal stress responses are partially defective in these mutants. To gain further insight into Ded1 translational regulation during stress, synthetic genetic array analysis was conducted in the presence of rapamycin with a ded1 mutant and a library of nonessential genes in Saccharomyces cerevisiae to identify positive and negative genetic interactions in an unbiased manner. Here, we report the results of this screen and subsequent network mapping and Gene Ontology-term analysis. Hundreds of candidate interactions were identified, which fell into expected categories, such as ribosomal proteins and amino acid biosynthesis, as well as unexpected ones, including membrane trafficking, sporulation, and protein glycosylation. Therefore, these results provide several specific directions for further comprehensive studies.A minority of individuals with eating disorders report being asked about their eating by health care professionals; delayed detection of eating disorders may contribute to poorer outcomes. The current study investigated common meal-related gastrointestinal symptoms (i.e., elevated fullness and bloating) as correlates of eating pathology that may be more readily disclosed to health professionals and indicate the need to assess for eating pathology. The current study also tested the hypothesis that elevated fullness and bloating are more strongly linked to eating pathology among those with higher body dissatisfaction. 281 university students (70.1% female, 84.3% white) completed gastrointestinal symptom and eating pathology assessments. Elevated fullness and bloating were each associated with increased purging, restrictive eating behaviors, and likelihood of having an eating disorder. Elevated fullness and bloating were more strongly linked to purging and probable eating disorder diagnosis with higher, relative to lower, body dissatisfaction. However, body dissatisfaction did not moderate the relationship between gastrointestinal symptoms and restrictive eating behaviors. Results indicate that elevated fullness and bloating are correlates of eating pathology. Healthcare professionals should consider and/or assess for eating pathology when elevated fullness and bloating are reported; further assessment of body dissatisfaction may be helpful in identifying purging behaviors.
Central post-stroke pain (CPSP) refers to neuropathic pain in areas of the body corresponding to stroke lesions. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is safe and effective against neuropathic pain. In this randomized double-blind placebo-controlled study, we studied the effect of duloxetine in CPSP patients.
Consecutive patients satisfying the inclusion criteria were enrolled in the study and were randomized in a simple 11 randomization to duloxetine and placebo groups. Baseline demographic, clinical and imaging data were obtained. Prespecified primary outcome was comparison of change in pain intensity from baseline to 4 weeks, as assessed on Numeric Rating Scale (NRS) in both groups. Prespecified secondary outcomes were comparison of change in average pain severity from baseline to 4 weeks as measured on Short-form McGill Pain Questionnaire-2 (SFMPQ-2) score and Pain Disability Index (PDI) score and comparison of Patient Global Impression of Change (PGIC) score at the end of 4 weekstine group (80.5%) than placebo group (43.9%) (p = 0.042).
Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain.
Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain.
Symptom-based automatic diagnostic system queries the patient's potential symptoms through continuous interaction with the patient and makes predictions about possible diseases. A few studies use reinforcement learning (RL) to learn the optimal policy from the joint action space of symptoms and diseases. However, existing RL (or Non-RL) methods focus on disease diagnosis while ignoring the importance of symptom inquiry. Although these systems have achieved considerable diagnostic accuracy, they are still far below its performance upper bound due to few turns of interaction with patients and insufficient performance of symptom inquiry. To address this problem, we propose a new automatic diagnostic framework called DxFormer, which decouples symptom inquiry and disease diagnosis, so that these two modules can be independently optimized. OT-82 The transition from symptom inquiry to disease diagnosis is parametrically determined by the stopping criteria. In DxFormer, we treat each symptom as a token, and formalize the symptom inquiry and disease diagnosis to a language generation model and a sequence classification model, respectively. We use the inverted version of Transformer, i.e. the decoder-encoder structure, to learn the representation of symptoms by jointly optimizing the reinforce reward and cross-entropy loss.
We conduct experiments on three real-world medical dialogue datasets, and the experimental results verify the feasibility of increasing diagnostic accuracy by improving symptom recall. Our model overcomes the shortcomings of previous RL-based methods. By decoupling symptom query from the process of diagnosis, DxFormer greatly improves the symptom recall and achieves the state-of-the-art diagnostic accuracy.
Both code and data are available at https//github.com/lemuria-wchen/DxFormer.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Ascorbic acid (ASC; vitamin C) is a weak chromophoric substance, so its presence cannot be determined directly by spectrophotometry.
This work aims to develop and validate a simple and ecofriendly analytical method for the determination of ASC concentration based on the reaction of ASC with the metal complex ferric salicylate.
The visible absorbance of ferric salicylate was found to be inversely proportional to the concentration of ASC. The possible mechanism of the reaction between ASC and ferric salicylate was investigated ferric salicylate was found to be reduced by ASC under the applied experimental conditions. Different parameters that may affect the reaction were also investigated ferric salicylate concentration, pH, ionic strength, and the time of reaction. The optimum concentration of ferric salicylate was found to be 1000 µM and the optimum pH was 5.5. The developed method was validated according to ICH guidelines.
The linearity range of the developed method was 5-70 µg/mL and the correlation coefficient was 0.9994. The limits of detection and quantitation were 0.38 µg/mL and 1.16 µg/mL, respectively. The method was successfully applied to the determination of ASC concentration in commercial Ruta-C60® tablets. The mean % recovery ± standard deviation was found to be 101.10 ± 0.70. The results were statistically compared to those obtained by a reported high performance liquid chromatographic method. Good agreement was observed.
The developed method is simple, fast, cost-effective, and suitable for routine pharmaceutical analysis of ASC.
The developed method is more sensitive than the other spectrophotometric methods reported for determination of ASC.
The developed method is more sensitive than the other spectrophotometric methods reported for determination of ASC.Understanding the dose-response for formaldehyde-induced nasal cancer in rats is complicated by (1) the uneven distribution of inhaled formaldehyde across the interior surface of the nasal cavity and, (2) the presence of endogenous formaldehyde (endoF) in the nasal mucosa. In this work, we used computational fluid dynamics (CFD) modeling to predict flux of inhaled (exogenous) formaldehyde (exogF) from air into tissue at the specific locations where DNA adducts were measured. Experimental work has identified DNA-protein crosslink (DPX) adducts due to exogF and deoxyguanosine (DG) adducts due to both exogF and endoF. These adducts can be considered biomarkers of exposure for effects of endoF and exogF on DNA that may be part of the mechanism of tumor formation. We describe a computational model linking CFD-predicted flux of formaldehyde from air into tissue, and the intracellular production of endoF, with the formation of DPX and DG adducts. We assumed that, like exogF, endoF can produce DPX. The model accurately reproduces exogDPX, exogDG, and endoDG data after inhalation from 0.7 to 15 ppm. The dose-dependent concentrations of exogDPX and exogDG are predicted to exceed the concentrations of their endogenous counterparts at about 2 and 6 ppm exogF, respectively. At all concentrations examined, the concentrations of endoDPX and exogDPX were predicted to be at least 10-fold higher than that of their DG counterparts. The modeled dose-dependent concentrations of these adducts are suitable to be used together with data on the dose-dependence of cell proliferation to conduct quantitative modeling of formaldehyde-induced rat nasal carcinogenicity.Thermal ablation has become a novel method for the treatment of pulmonary nodules, but the short-time evaluation of the ablation effect is mainly based on computed tomography images. We report a case of local tumour residue after microwave ablation, which was confirmed by pathology after lobectomy. This case alerts us that thermal ablation should not be the preferred treatment for operable pulmonary nodules.Autistic people are on average more likely to experience poor health than people who are not autistic. Health checks have been shown to improve access to effective healthcare. This study investigated people's views about a primary care health check for autistic adults. We held discussion groups and interviewed autistic adults, adults with intellectual disabilities, supporters and health professionals. People wanted the health check to look at a person's physical and mental health, and how they were doing socially. They thought people should be able to share information about their needs and the reasonable adjustments they would like before the health check. They wanted healthcare services to change the way they communicate with autistic people, such as being able to book appointments online rather than by telephone. They wanted a choice in how the health check was completed, with video call or email offered as well as face-to-face appointments. People thought further training of primary care staff on autism was needed, to increase awareness of the diversity of experiences of autistic people and ways in which difficulties, such as pain, may present differently to non-autistic people.
Homepage: https://www.selleckchem.com/products/ot-82.html
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