Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry.

Melanoma is the most aggressive type of skin cancer due to its high capability of developing metastasis and acquiring chemoresistance. Altered redox homeostasis induced by increased reactive oxygen species is associated with melanomagenesis through modulation of redox signaling pathways. Dysfunctional endothelial nitric oxide synthase (eNOS) produces superoxide anion (O2-•) and contributes to the establishment of a pro-oxidant environment in melanoma. Although decreased tetrahydrobiopterin (BH4) bioavailability is associated with eNOS uncoupling in endothelial and human melanoma cells, in the present work we show that eNOS uncoupling in metastatic melanoma cells expressing the genes from de novo biopterin synthesis pathway Gch1, Pts, and Spr, and high BH4 concentration and BH4:BH2 ratio. Western blot analysis showed increased expression of Nos3, altering the stoichiometry balance between eNOS and BH4, contributing to NOS uncoupling. Both treatment with L-sepiapterin and eNOS downregulation induced increased nitric oxide (NO) and decreased O2• levels, triggering NOS coupling and reducing cell growth and resistance to anoikis and dacarbazine chemotherapy. Moreover, restoration of eNOS activity impaired tumor growth in vivo. Finally, NOS3 expression was found to be increased in human metastatic melanoma samples compared with the primary site. eNOS dysfunction may be an important mechanism supporting metastatic melanoma growth and hence a potential target for therapy.

The combined use of chemical and biochemical markers in Rutilus rutilus to assess the effect of dredging in the lower course of the Ebro River.

The lower course of the Ebro River is polluted with high concentrations of organochlorine compounds dumped by a chloro-alkali plant during the last century. A remediation plan, including building of a protective wall, removal and disposal of polluted sediments started in 2012. With the aim of assessing the effects of dredging of contaminated sediments and potential alterations of water quality, areas located upstream (RR) and downstream (BE, A) the chemical plant (FL) were monitored prior (October 2012) and during dredging (June 2013) using roach (Rutilus rutilus) as sentinel organisms. Concentrations of organochlorine compounds (OCs) in fish muscle and biliary levels of polycyclic aromatic hydrocarbons (PAHs), galaxolide (HHCB) and alkyphenols (APEs) were determined together with selected enzymatic activities (7-ethoxyresorufin-O-deethylase (EROD), 7-benzyloxy-4-trifluoromethyl-coumarin O-debenzyloxylase (BFCOD) and UDP-glucuronyltransferase (UGT)) in the liver. The obtained results proved the effectiveness of the wall retaining suspended particles and avoiding further contamination of downstream sites as fish sampled at downstream sites showed up to 9-fold higher concentrations of OCs in muscle during wall construction than during dredging. EROD and UGT activities were induced in fish from downstream sites; however, no clear response to the observed pollution gradient was detected.

Nitroarachidonic acid (NO2AA) inhibits protein disulfide isomerase (PDI) through reversible covalent adduct formation with critical cysteines.

BACKGROUND: Nitroarachidonic acid (NO2AA) exhibits pleiotropic anti-inflammatory actions in a variety of cell types. We have recently shown that NO2AA inhibits phagocytic NADPH oxidase 2 (NOX2) by preventing the formation of the active complex. Recent work indicates the participation of protein disulfide isomerase (PDI) activity in NOX2 activation. Cysteine (Cys) residues at PDI active sites could be targets for NO2AA- nitroalkylation regulating PDI activity which could explain our previous observation. METHODS: PDI reductase and chaperone activities were assessed using the insulin and GFP renaturation methods in the presence or absence of NO2AA. To determine the covalent reaction with PDI as well as the site of reaction, the PEG-switch assay and LC-MS/MS studies were performed. RESULTS AND CONCLUSIONS: We determined that both activities of PDI were inhibited by NO2AA in a dose- and time- dependent manner and independent from release of nitric oxide. Since nitroalkenes are potent electrophiles and PDI has critical Cys residues for its activity, then formation of a covalent adduct between NO2AA and PDI is feasible. To this end we demonstrated the reversible covalent modification of PDI by NO2AA. Trypsinization of modified PDI confirmed that the Cys residues present in the active site a' of PDI were key targets accounting for nitroalkene modification. GENERAL SIGNIFICANCE: PDI may contribute to NOX2 activation. As such, inhibition of PDI by NO2AA might be involved in preventing NOX2 activation. Future work will be directed to determine if the covalent modifications observed play a role in the reported NO2AA inhibition of NOX2 activity.

Sex steroids and metabolic responses in mussels Mytilus galloprovincialis exposed to drospirenone.

Drospirenone (DRO) is a synthetic progestin derived from 17α-spironolactone with a pharmacological mechanism of action similar to progesterone. Despite its wide use as pharmaceutical and consequent continuous release into the aquatic environment, DRO effects have been poorly investigated on aquatic biota. In order to unravel the toxicity mechanisms of DRO, mussels Mytilus galloprovincialis were exposed for 7 days to different concentrations of DRO, namely 20ng/L (Low; L), 200ng/L (Medium; M), 2000ng/L (High; H) and 10µg/L (Super High; SH) nominal doses. Following exposure, no significant effect was observed on gonad maturation of treated and untreated mussels. The levels of progesterone (P4) and testosterone (T) were measured in mantle/gonad tissues and no significant alteration detected after exposure. However, the application of a protonic nuclear magnetic resonance (1H NMR)-based metabolomics approach enabled a comprehensive assessment of DRO effects in mussels. Specifically, 1H NMR metabolic fingerprints of digestive glands of DRO treated mussel groups were clearly separated from each other and from controls through a principal component analysis (PCA). Moreover, a number of metabolites involved in different metabolic pathways were found to significantly change in DRO-exposed mussels compared to control, suggesting the occurrence of alterations in energy metabolism, amino acids metabolism, and glycerophospholipid metabolism. Overall, despite no changes in gonad maturation and steroids levels were recorded in mussels after DRO exposure, the metabolomics approach demonstrated its effectiveness and high sensitivity in elucidating DRO-induced metabolic disturbances in marine mussels, and thus its usefulness in the environmental risk assessment of pharmaceuticals.

Modulation of MAPK and NF-954;B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats.

BACKGROUND/AIMS: Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats. METHODS AND RESULTS: Four months after surgery, rats were assigned to Sham, myocardial infarction (MI)-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 ± 0.056; MI-C 0.223 ± 0.073; MI-NAC 0.136 ± 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-954;B p65 subunit was reduced; p-Ser276 in p65 and I954;B was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-954;B p65 subunit, but decreased p-Ser276 and p-Ser536. CONCLUSION: N-acetylcysteine modulates MAPK and NF-954;B signaling pathways in soleus muscle of HF rats.

A randomized controlled trial testing an Internet delivered cost-benefit approach to weight loss maintenance.

Weight loss maintenance is a significant challenge in obesity treatment. During maintenance the "costs" of adhering to weight management behaviors may outweigh the "benefits." This study examined the efficacy of a novel approach to weight loss maintenance based on modifying the cost-benefit ratio. Individuals who achieved a 5% weight loss (N=75) were randomized to one of three, 10-month maintenance interventions. All interventions were delivered primarily via the Internet. The Standard arm received traditional weight maintenance strategies. To increase benefits, or rewards, for maintenance behaviors, the two cost-benefit intervention conditions received weekly monetary rewards for self-monitoring and social reinforcement via e-coaching. To decrease behavioral costs (boredom) and increase novelty, participants in the cost-benefit conditions also monitored different evidence-based behaviors every two weeks (e.g., Weeks 1 & 2: steps; Week 3 & 4: red foods). The primary difference between the cost-benefit interventions was type of e-coach providing social reinforcement: Professional (CB Pro) or Peer (CB Peer). Study procedures took place in Providence, RI from 2013 to 2014. Retention was 99%. There were significant group differences in weight regain (p=.01). The Standard arm gained 3.5±5.7kg. In contrast, participants in CB Pro and CB Peer lost an additional 1.8±7.0kg and 0.5±6.4kg, respectively. These results suggest that an Internet delivered cost-benefit approach to weight loss maintenance may be effective for long-term weight control. In addition, using peer coaches to provide reinforcement may be a particularly economic alternative to professionals. These data are promising and provide support for a larger, longer trial.

Influence of N- acetylcysteine on oxidative stress in slow-twitch soleus muscle of heart failure rats.

BACKGROUND: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. METHODS AND RESULTS: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47(phox) was lower in MI-C than Sham. NAC decreased NOX4 and p22(phox) expression. CONCLUSIONS: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.

Hours of sleep and associated factors in college students during the COVID-19 pandemic.

BACKGROUND: Sleep alterations are common in college students, particularly during the COVID-19 pandemic. Sociodemographic factors may predict these alterations in this population. OBJECTIVE: To identify the sociodemographic factors and health characteristics associated with the number of hours of sleep of college students during the COVID-19 pandemic. METHODS: This was a cross-sectional study carried out with 244 university students from a multicampi public university in the State of Bahia, Northeast Brazil. Data collection was performed online and participants answered a specific questionnaire to assess sleep hours, sociodemographic and health variables. RESULTS: Significant associations were observed between hours of sleep and older students (odds ratio adjusted -ORaj: 3.75; 95% Confidence Interval -CI: 1.81-7.75; p < 0.01), attending the final semesters (ORaj: 1.85; 95% CI: 1.05-3.25; p < 0.03), and who reported having some disease (ORaj: 2.18; 95% CI: 1.05-4.50; p < 0.03) with greater chances of getting less sleep. However, those who used tobacco (ORaj: 0.08; 95% CI: 0.01-0.45; p < 0.001) were likely to have more hours of sleep per night. CONCLUSION: Sleep restriction was common among participating college students, which has likely intensified due to the COVID-19 pandemic and its restrictions. This encourages specific public health actions, contemplating the health and hours of sleep of this population.

Rare Association of Autoimmune Limbic Encephalitis and Stiff Person Syndrome.

Antibodies to Glutamic Acid Decarboxylase (GAD) have been implicated in the pathogenesis of both autoimmune Limbic Encephalitis (LE) and Stiff Person Syndrome (SPS). However, their association is quite rare. We present a case of a 48-year-old Caucasian female who presented with symptoms of recurrent severe headaches, behavioral and cognitive dysfunction, and an episode of seizure. She was found to have high titers of anti-GAD65 antibodies in both cerebrospinal fluid and serum. She was diagnosed with LE and SPS, and was started on immunosuppressive therapy with steroids and intravenous immunoglobulins (IVIG). The patient responded well to treatment with improvement in her symptoms.

Factors Associated with the Lifestyle of Pediatric Healthcare Professionals during the COVID-19 Pandemic.

The objective of this study was to analyze the association between sociodemographic and occupational variables with the lifestyle of health professionals in pediatric units during the COVID-19 pandemic. A cross-sectional study was conducted with 407 health professionals working in four pediatric health units in the State of Bahia, northeast Brazil. The Fantastic Lifestyle Questionnaire and a questionnaire with sociodemographic and employment variables self-applied via Google Forms were used. The final binary logistic regression models revealed significant associations between those who received 3 to 5 minimum wages, without a marital relationship and with more than one employment relationship. Data suggest that these sociodemographic and occupational profiles are more exposed to risky lifestyle behaviors. The findings of this study demonstrated the need for greater attention to the health of health professionals in the pediatric field, as well as the promotion of initiatives that seek to value the work of these professionals and reduce the damage caused to their lifestyle, especially in a pandemic scenario.

Acute Nephrotic Syndrome and Otosyphilis.

Syphilis, also known as the "the great masquerader," is a re-emerging infectious disease in the Western world, and may present with various signs and symptoms, making it difficult to distinguish from other diseases. Nephrotic syndrome due to syphilis has been rarely reported in modern times. Here, we describe a young male with acute hearing loss and peripheral edema, found to have acute nephrotic syndrome in the setting of otosyphilis. Given increasing incidence of syphilis, physicians must remain alert to syphilis as a possible cause of nephrotic syndrome.

Effectiveness of "run-ins" at predicting adherence in a behavioral weight loss efficacy trial.

There is limited research on whether run-in procedures predict participant adherence during behavioral efficacy trials. This study examined whether information from behavioral run-ins (food diary completion, questionnaire completion, and staff interview) predict intervention adherence, trial retention, and trial outcomes in a behavioral weight loss trial. Using run-in data, trial staff predicted which participants would have high, moderate, or low trial adherence. Participants with predicted high or moderate adherence were randomized. Results showed that predicted high adherers had better intervention adherence (session attendance and completion of self-monitoring records) and superior trial outcomes (i.e. weight loss). Run-in data did not predict trial retention. Results suggest that run-ins may be effective at identifying participants adherent to intervention protocols, thereby enhancing internal validity of behavioral efficacy trials.

Comprehensive analysis of the GALACTINOL SYNTHASE (GolS) gene family in citrus and the function of CsGolS6 in stress tolerance.

Galactinol synthase (GolS) catalyzes the first and rate-limiting step in the synthesis of raffinose family of oligosaccharides (RFOs), which serve as storage and transport sugars, signal transducers, compatible solutes and antioxidants in higher plants. The present work aimed to assess the potential functions of citrus GolS in mechanisms of stress response and tolerance. By homology searches, eight GolS genes were found in the genomes of Citrus sinensis and C. clementina. Phylogenetic analysis showed that there is a GolS ortholog in C. clementina for each C. sinensis GolS, which have evolved differently from those of Arabidopsis thaliana. Transcriptional analysis indicated that most C. sinensis GolS (CsGolS) genes show a low-level tissue-specific and stress-inducible expression in response to drought and salt stress treatments, as well as to 'Candidatus Liberibacter asiaticus' infection. CsGolS6 overexpression resulted in improved tobacco tolerance to drought and salt stresses, contributing to an increased mesophyll cell expansion, photosynthesis and plant growth. Primary metabolite profiling revealed no significant changes in endogenous galactinol, but different extents of reduction of raffinose in the transgenic plants. On the other hand, a significant increase in the levels of metabolites with antioxidant properties, such as ascorbate, dehydroascorbate, alfa-tocopherol and spermidine, was observed in the transgenic plants. These results bring evidence that CsGolS6 is a potential candidate for improving stress tolerance in citrus and other plants.

Tobacco smoke induces ventricular remodeling associated with an increase in NADPH oxidase activity.

BACKGROUND: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. METHODS: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. RESULTS: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-γ, TNF-α and IL-10 were not different between the groups. CONCLUSION: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke.

Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation.

The physiological effects of nitroglycerin as a potent vasodilator have long been documented. However, the molecular mechanisms by which nitroglycerin exerts its biological functions are still a matter of intense debate. Enzymatic pathways converting nitroglycerin to vasoactive compounds have been identified, but none of them seems to fully account for the reported clinical observations. Here, we demonstrate that nitroglycerin triggers constitutive nitric oxide synthase (NOS) activation, which is a major source of NO responsible for low-dose (1-10 nM) nitroglycerin-induced vasorelaxation. Our studies in cell cultures, isolated vessels, and whole animals identified endothelial NOS activation as a fundamental requirement for nitroglycerin action at pharmacologically relevant concentrations in WT animals.

Fecaloma - A Common Problem, Uncommon Dimensions.

Chronic constipation and fecal impaction are common in older individuals but can also be found in younger patients with cognitive and psychiatric illnesses. The diagnosis of fecal impaction and, the assessment of severity are best performed clinically. Here, we present a case of a 30-year-old autistic individual where limited history was obtainable and further imaging helped to urgently diagnose a 47 x 15.6 x 12 cm stool ball, causing significant mass effect of surrounding intra-abdominal structures. Fecal disimpaction and aggressive bowel regimen prevented the pathological effects of severe fecal retention.

Physical exercise is effective for neuropsychiatric symptoms in Alzheimer's disease: a systematic review.

BACKGROUND: Neuropsychiatric symptoms are disorders frequently seen in Alzheimer's disease. These symptoms contribute to reduction of brain reserve capacity and, in addition, they present unfavorable implications, such as: poor prognosis for the disease, increased functional decline, increased burden on the caregiver and institutionalization. This scenario makes neuropsychiatric symptoms one of the biggest problems in Alzheimer's disease, and gives rise to a need for treatments focused on improving these symptoms. Sow progress in drug trials has led to interest in exploring non-pharmacological measures for improving the neuropsychiatric symptoms of Alzheimer's disease, such as physical exercise. OBJECTIVE: To ascertain the effect of exercise on the neuropsychiatric symptoms of Alzheimer's disease and its implications. METHODS: This was a systematic review of effective longitudinal research, conducted by searching for articles in the PubMed, Web of Science, CINAHL and Scopus electronic databases, from 2009 to 2019. Studies in which the sample consisted of elderly people aged 65 years old or over with a diagnosis of Alzheimer's disease were included. Initially 334 articles were identified. After exclusions, 21 articles remained to be read in full. From these, five articles fitted the eligibility criteria, and a further two articles were added through manual searches in the references of the articles found. RESULTS: Out of the seven articles analyzed in this review, five studies revealed that physical exercise had a positive effect on the neuropsychiatric symptoms of Alzheimer's disease. CONCLUSION: This systematic review indicated that physical exercise is a favorable non-pharmacological means for attenuating the neuropsychiatric symptoms of elderly people with Alzheimer's disease, with special attention to aerobic exercises.

PDIA1 acts as master organizer of NOX1/NOX4 balance and phenotype response in vascular smooth muscle.

Changes in vascular smooth muscle cell (VSMC) phenotype underlie disease pathophysiology and are strongly regulated by NOX NADPH oxidases, with NOX1 favoring synthetic proliferative phenotype and NOX4 supporting differentiation. Growth factor-triggered NOX1 expression/activity strictly depends on the chaperone oxidoreductase protein disulfide isomerase-A1 (PDIA1). Intracellular PDIA1 is required for VSMC migration and cytoskeleton organization, while extracellular PDIA1 fine-tunes cytoskeletal mechanoadaptation and vascular remodeling. We hypothesized that PDIA1 orchestrates NOX1/NOX4 balance and VSMC phenotype. Using an inducible PDIA1 overexpression model in VSMC, we showed that early PDIA1 overexpression (for 24-48 h) increased NOX1 expression, hydrogen peroxide steady-state levels and spontaneous VSMC migration distances. Sustained PDIA1 overexpression for 72 h and 96 h supported high NOX1 levels while also increasing NOX4 expression and, remarkably, switched VSMC phenotype to differentiation. Differentiation was preceded by increased nuclear myocardin and serum response factor-response element activation, with no change in cell viability. Both NOX1 and hydrogen peroxide were necessary for later PDIA1-induced VSMC differentiation. In primary VSMC, PDIA1 knockdown decreased nuclear myocardin and increased the proliferating cell nuclear antigen expression. Newly-developed PDIA1-overexpressing mice (TgPDIA1) exhibited normal general and cardiovascular baseline phenotypes. However, in TgPDIA1 carotids, NOX1 was decreased while NOX4 and calponin expressions were enhanced, indicating overdifferentiation vs. normal carotids. Moreover, in a rabbit overdistension injury model during late vascular repair, PDIA1 silencing impaired VSMC redifferentiation and NOX1/NOX4 balance. Our results suggest a model in which PDIA1 acts as an upstream organizer of NOX1/NOX4 balance and related VSMC phenotype, accounting for baseline differentiation setpoint.

Aerobic Exercise During Advance Stage of Uncontrolled Arterial Hypertension.

AIM: To evaluate the influence of physical training on myocardial function, oxidative stress, energy metabolism, and MAPKs and NF-κB signaling pathways in spontaneously hypertensive rats (SHR), at advanced stage of arterial hypertension, which precedes heart failure development. METHODS: We studied four experimental groups: normotensive Wistar rats (W, n = 27), trained W (W-EX, n = 31), SHR (n = 27), and exercised SHR (SHR-EX, n = 32). At 13 months old, the exercise groups underwent treadmill exercise 5 days a week for 4 months. In vitro myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Antioxidant enzyme activity and energy metabolism were assessed by spectrophotometry. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was analyzed by lucigenin reduction and protein expression by Western blot. Statistical analyzes: ANOVA and Tukey or Kruskal-Wallis and Dunn tests. RESULTS: SHR-EX had a lower frequency of heart failure features than SHR. Myocardial function and antioxidant enzyme activity were better in SHR-EX than SHR. Lipid hydroperoxide concentration, and phosphorylated JNK and total IkB protein expression were higher in hypertensive than control groups. Malondialdehyde, NADPH oxidase activity, total JNK, phosphorylated p38, phosphorylated and total p65 NF-κB, and phosphorylated IkB did not differ between groups. Protein expression from total p38, and total and phosphorylated ERK were higher in SHR than W. Lactate dehydrogenase and phosphorylated ERK were lower and citrate synthase and ß-hydroxyacyldehydrogenase were higher in SHR-EX than SHR. CONCLUSION: Exercise improves physical capacity, myocardial function, and antioxidant enzyme activity; reduces the frequency of heart failure features and ERK phosphorylation; and normalizes energy metabolism in SHR.

Patient-provided e-support in reduced intensity obesity treatment: The INSPIRE randomized controlled trial.

OBJECTIVE: There are two types of patient supporters, peers (two individuals initiating health behavior change who support one another) and mentors (a previously successful patient who supports incoming patients). Social comparison theory suggests that peers and mentors may elicit social comparison processes (patients may compare their progress to that of their peer/mentor), and these social comparisons could impact treatment outcomes. This randomized controlled trial is the first to examine the differential impact of peers and mentors on obesity treatment outcomes and social comparison processes when added to reduced intensity treatment. METHOD: Participants (N = 278) were randomly assigned to reduced intensity behavioral weight loss treatment alone (rBWL), rBWL plus peer e-support (rBWL + Peer), or rBWL plus mentor e-support (rBWL + Mentor). rBWL involved periodic group sessions that decreased over time; when group sessions decreased, intensity of peer/mentor e-support increased. Weight and social comparison processes were assessed throughout the 12-month intervention. RESULTS: There was a significant treatment effect; when group sessions became less frequent and peer/mentor e-support became more frequent, rBWL + Peer had significantly greater weight loss than rBWL alone, and rBWL + Mentor was not significantly different from the other two. Social comparison processes differed by treatment arm; rBWL + Peer participants tended to report more lateral social comparisons ("my weight loss progress is 'similar' to my peer's"), whereas rBWL + Mentor participants reported more upward comparisons ("my weight loss progress is 'worse than' my mentor's"). Upward comparisons were associated with poorer weight loss outcomes. CONCLUSIONS: Peer e-support may be an effective, low-cost, sustainable method for improving longer-term weight loss outcomes in reduced intensity obesity treatment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).