Extending Expectancy Theory to Food Intake: Effect of a Simulated Fast-Food Restaurant on Highly and Minimally Processed Food Expectancies.

Unhealthy diets are widespread and linked to a number of detrimental clinical outcomes. The current preregistered experiment extended Expectancy Theory into the study of food intake; specifically, we tested whether a fast-food restaurant affects food expectancies, or the emotions one expects to feel while eating highly (e.g., pizza) and minimally (e.g., carrots) processed foods. Participants (N = 200, M age = 18.79) entered a simulated fast-food restaurant or a neutral space, completed questionnaires, and engaged in a 'bogus' taste test. The simulated fast-food restaurant increased positive highly-processed food expectancies (d = 0.29). Palatable eating coping motives scores did not moderate the effect; however, this clinically-relevant pattern of eating behavior was associated with greater positive highly-processed food expectancies. In addition, there was an indirect effect of the fast-food restaurant on ad libitum food intake through positive highly-processed food expectancies. Reducing positive highly-processed food expectancies may improve diet, which may broadly impact health.

The Role of Resistance Training Dosing on Pain and Physical Function in Individuals With Knee Osteoarthritis: A Systematic Review.

CONTEXT: Dosing parameters are needed to ensure the best practice guidelines for knee osteoarthritis. OBJECTIVE: To determine whether resistance training affects pain and physical function in individuals with knee osteoarthritis, and whether a dose-response relationship exists. Second, we will investigate whether the effects are influenced by Kellgren-Lawrence grade or location of osteoarthritis. DATA SOURCES: A search for randomized controlled trials was conducted in MEDLINE, Embase, and CINAHL, from their inception dates, between November 1, 2018, and January 15, 2019. Keywords included knee osteoarthritis, knee joint, resistance training, strength training, and weight lifting. STUDY SELECTION: Inclusion criteria were randomized controlled trials reporting changes in pain and physical function on humans with knee osteoarthritis comparing resistance training interventions with no intervention. Two reviewers screened 471 abstracts; 12 of the 13 studies assessed were included. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2. DATA EXTRACTION: Mean baseline and follow-up Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and standard deviations were extracted to calculate the standard mean difference. Articles were assessed for methodological quality using the CONSORT (Consolidated Standards of Reporting Trials) 2010 scale and Cochrane Collaboration tool for assessing risk of bias. RESULTS: The 12 included studies had high methodological quality. Of these, 11 studies revealed that resistance training improved pain and/or physical function. The most common regimen was a 30- to 60-minute session of 2 to 3 sets of 8 to 12 repetitions with an initial resistance of 50% to 60% of maximum resistance that progressed over 3 sessions per week for 24 weeks. Seven studies reported Kellgren-Lawrence grade, and 4 studies included osteoarthritis location. CONCLUSION: Resistance training improves pain and physical function in knee osteoarthritis. Large effect sizes were associated with 24 total sessions and 8- to 12-week duration. No optimal number of repetitions, maximum strength, or frequency of sets or repetitions was found. No trends were identified between outcomes and location or Kellgren-Lawrence grade of osteoarthritis.

Evolutionary Divergence of Gene and Protein Expression in the Brains of Humans and Chimpanzees.

Although transcriptomic profiling has become the standard approach for exploring molecular differences in the primate brain, very little is known about how the expression levels of gene transcripts relate to downstream protein abundance. Moreover, it is unknown whether the relationship changes depending on the brain region or species under investigation. We performed high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses on two regions of the human and chimpanzee brain: The anterior cingulate cortex and caudate nucleus. In both brain regions, we found a lower correlation between mRNA and protein expression levels in humans and chimpanzees than has been reported for other tissues and cell types, suggesting that the brain may engage extensive tissue-specific regulation affecting protein abundance. In both species, only a few categories of biological function exhibited strong correlations between mRNA and protein expression levels. These categories included oxidative metabolism and protein synthesis and modification, indicating that the expression levels of mRNA transcripts supporting these biological functions are more predictive of protein expression compared with other functional categories. More generally, however, the two measures of molecular expression provided strikingly divergent perspectives into differential expression between human and chimpanzee brains: mRNA comparisons revealed significant differences in neuronal communication, ion transport, and regulatory processes, whereas protein comparisons indicated differences in perception and cognition, metabolic processes, and organization of the cytoskeleton. Our results highlight the importance of examining protein expression in evolutionary analyses and call for a more thorough understanding of tissue-specific protein expression levels.

Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition.

The S-nitrosoglutathione-metabolizing enzyme, GSNO reductase (GSNOR), has emerged as an important regulator of protein S-nitrosylation. GSNOR ablation is protective in models of asthma and heart failure, raising the idea that GSNOR inhibitors might hold therapeutic value. Here, we investigated the effects of a small molecule inhibitor of GSNOR (GSNORi) in mouse RAW 264.7 macrophages. We found that GSNORi increased protein S-nitrosylation in cytokine-stimulated cells, and we utilized stable isotope labeling of amino acids in cell culture (SILAC) to quantify the cellular response to this "nitrosative stress". The expression of several cytokine-inducible immunomodulators, including osteopontin, cyclooxygenase-2, and nitric oxide synthase isoform 2 (NOS2), were decreased by GSNORi. In addition, selective targets of the redox-regulated transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-including heme oxygenase 1 (HO-1) and glutamate cysteine ligase modulatory subunit-were induced by GSNORi in a NOS2- and Nrf2-dependent manner. In cytokine-stimulated cells, Nrf2 protected from GSNORi-induced glutathione depletion and cytotoxicity and HO-1 activity was required for down-regulation of NOS2. Interestingly, GSNORi also affected a marked increase in NOS2 protein stability. Collectively, these data provide the most complete description of the global effects of GSNOR inhibition and demonstrate several important mechanisms for inducible response to GSNORi-mediated nitrosative stress.

Risk factors for subject withdrawals in clinical trials evaluating glaucoma medications.

BACKGROUND: To evaluate risk factors for subject withdrawals from multicenter clinical trials evaluating glaucoma medications. METHODS: An analysis of prospective, randomized, multicenter, parallel, active-controlled clinical trials with 70 subjects/treatment arm published from 1996-2008. RESULTS: We analyzed 36 glaucoma studies including 17,511 subjects at 1,294 clinical sites. There were 2,060 (12%) subject withdrawals with 669 (32%) for administrative errors, 945 (46%) for adverse events (AEs), 197 (10%) for inadequate intraocular pressure (IOP) control and 249 (12%) for unknown reasons. By multilinear regression analysis, no positive risk factors for early subject withdrawals were observed following a Bonferroni correction (p > or = 0.01). A positive correlation was observed for medication errors and protocol violations to withdrawals due to ocular AEs and total administrative errors (p < 0.0001). Protocol violations alone were correlated to subject withdrawals for any AE (total/month) and systemic AEs (p < 0.0001). Females and Caucasians were correlated to medication errors (p < 0 .0001). Among medical therapies, alpha-agonists, beta-blockers, the carbonic anhydrase inhibitor/beta-blocker fixed combination and prostaglandins were correlated with systemic AEs (p < or = 0.005) while the alpha-agonists were correlated with withdrawals for poor IOP control (p = 0.00056). CONCLUSIONS: Subject withdrawals from clinical trials for total administrative errors or AEs potentially might be reduced by choosing sites with lower historical rates of protocol violations or medication dispensing errors. Drug class choice also may influence subject withdrawals for AEs and poor IOP control.

Effects of styrene and styrene oxide on glutathione-related antioxidant enzymes.

Styrene is both hepatotoxic and pneumotoxic in mice. Its mode of action is not clear, but it may be related to oxidative stress including a very large decrease in reduced glutathione (GSH). The current studies evaluated if: (1) the more toxic R-styrene oxide had a greater effect on reduced GSH levels than the less toxic S-styrene oxide, (2) the ratio of reduced to oxidized forms of glutathione was altered by styrene or styrene oxide, (3) other enzymes involved in the oxidant status of the cell, namely glutathione reductase, glutathione peroxidase and gamma-glutamylcysteine synthetase were altered, and (4) lipid peroxidation, as measured by the determination of malondialdehyde, increased. R-Styrene oxide (300mg/kg, ip) caused greater decreases in mouse liver and lung GSH than did S-styrene oxide (300mg/kg, ip). Styrene (600mg/kg, ip) caused decreases in both GSH and GSSG in both liver and lung. Styrene and styrene oxide did not cause significant increases in lipid peroxidation in either liver or lung. Styrene and styrene oxide had minimal effects on glutathione reductase and glutathione peroxidase in liver and lung. Styrene increased gamma-glutamylcysteine synthetase activity. The results suggest that while styrene and its metabolite styrene oxide cause significant decreases in GSH levels, they have little effect on the enzymes glutathione reductase and glutathione peroxidase and that in response to decreased glutathione levels there is an increase in its synthesis via induction of gamma-glutamylcysteine synthetase activity.

Ring-oxidized metabolites of styrene contribute to styrene-induced Clara-cell toxicity in mice.

Styrene produced cytotoxicity in the terminal bronchioles of mice, but not rats, due to metabolites produced in situ by CYP2F2 metabolism. It has generally been presumed that styrene toxicity is mediated by styrene 7,8-oxide, but styrene oxide is not much more toxic than styrene. In contrast, ring-oxidized metabolites (4-vinylphenol or its metabolites) induce much greater toxicity. Administration of 4-vinylphenol results in pneumotoxicity, based on analysis of bronchoalveolar lavage fluid (BALF) at a 5- to 10 fold lower dose than does styrene oxide. In the current research, studies demonstrated that ip administration of 4-vinylphenol for 14 consecutive days at dosages of 6, 20, or 60 mg/kg/d (split into 3 doses) produced cytotoxicity in the terminal bronchioles of mice, but not rats. While higher doses of 4-vinylphenol produced adverse effects in both liver and lung, no liver toxicity was seen in mice exposed to 60 mg/kg/d for 14 d. Approximately 4 d was required for BALF parameters to return to normal following a single administration of 4-vinylphenol. These studies add further support for the role of ring-oxidized metabolites in the pneumotoxicity induced by styrene in mice and the lack thereof in rats.

Comparison of the depletion of glutathione in mouse liver and lung following administration of styrene and its metabolites styrene oxide and 4-vinylphenol.

Styrene is hepatotoxic and pneumotoxic in mice. Its major metabolite styrene oxide and its minor, but potent, metabolite 4-vinylphenol cause similar toxicities. Styrene and styrene oxide cause decreases in reduced glutathione levels in tissues. The current studies examined styrene and styrene oxide in a time and dose-dependent manner and 4-vinylphenol in a time dependent fashion. Styrene (600 mg/kg, 5.8 mmol/kg ip) caused decreased GSH levels in both liver and lung within one hour. A maximum was seen at three hours with return to control levels by 12 h. Lower doses also caused changes in a dose-dependent fashion. For styrene oxide, similar findings were observed with a dose of 300 mg/kg (2.5 mmol/kg). GSH levels in liver, but not lung, returned to control by 6 h. Again a dose response was found for both tissues. While 4-vinylphenol (100 mg/kg, 0.83 mmol/kg) was administered at a dose known to be more hepatotoxic and more pneumotoxic than styrene or styrene oxide and it caused decreased GSH levels, the degree of depletion was less compared to styrene and styrene oxide. In general the lung was more affected by these agents than was liver. The decreases in GSH suggest the possibility that the toxicity of styrene in lung and liver may be related to a profound but reversible oxidative stress in these tissues.