The associations between attentional bias to food cues, parent-report appetitive traits, and concurrent adiposity among adolescents.

OBJECTIVE: To assess whether attentional bias to food cues and appetitive traits are independently and interactively associated with adiposity in adolescents. METHOD: Eighty-five adolescents, 14-17-years had their attentional bias to food images measured in a sated state by computing eye tracking measures of attention (first fixation duration, cumulative fixation duration) to food and control distractor images that bordered a computer game. Parents reported adolescent appetitive traits including the food approach domains of enjoyment of food, food responsiveness, emotional overeating, and the food avoidance domains of satiety responsiveness and emotional overeating through the Children's Eating Behavior Questionnaire. RESULTS: First fixation bias to food cues was positively associated with enjoyment of food, and negatively associated with satiety responsiveness. In a series of regression models adjusted for relevant covariates, first fixation bias to food cues (ß = 0.83, p = 0.007), higher food responsiveness (ß = 0.74, p < 0.001), higher emotional overeating (ß = 0.51, p = 0.002), and a composite appetite score (ß = 1.42, p < 0.001) were each significantly associated with greater BMI z-scores. In models assessing the interactive effects between attentional bias and appetitive traits, higher first fixation bias to food cues interacted synergistically with food responsiveness and emotional overeating in relation to BMI z-score. A synergistic interaction between first fixation bias to food cues and the composite appetite score in relation to BMI z-score was also observed. CONCLUSION: Individuals with high attentional bias to food cues and obesogenic appetitive traits may be particularly susceptible to weight gain.

Population risk factors for late-stage presentation of cervical cancer in sub-Saharan Africa.

BACKGROUND: Cervical cancer is the most prevalent malignancy in sub-Saharan Africa (SSA) with many women only seeking professional help when they are experiencing symptoms, implying late-stage malignancy and higher mortality rates. This ecological study assesses population-level exposures of SSA women to the numerous risk factors for HPV infection and cervical cancer, against late-stage presentation of cervical cancer. MATERIALS AND METHOD: A literature review revealed the relevant risk factors in SSA. Open-access databases were mined for variables closely representing each risk factor. A proxy for late-stage presentation was used (ratio of incidence-to-mortality, IMR), and gathered from IARC's GLOBOCAN 2012 database. Variables showing significant correlation to the IMR were used in stepwise multiple regression to quantify their effect on the IMR. RESULTS: Countries with high cervical cancer mortality rates relative to their incidence have an IMR nearer one, suggesting a larger proportion of late-stage presentation. Western Africa had the lowest median IMR (1.463), followed by Eastern Africa (IMR = 1.595) and Central Africa (IMR = 1.675), whereas Southern Africa had the highest median IMR (1.761). Variables selected for the final model explain 65.2% of changes seen in the IMR. Significant predictors of IMR were GDP (coefficient = 2.189 × 10-6, p = 0.064), HIV infection (-1.936 × 10-3, p = 0.095), not using a condom (-1.347 × 10-3, p = 0.013), high parity (-1.744 × 10-2, p = 0.008), and no formal education (-1.311 × 10-3, p < 0.001). CONCLUSION: Using an IMR enables identification of factors predicting late-stage cervical cancer in SSA including: GDP, HIV infection, not using a condom, high parity and no formal education.

Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat.

Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo.

Cardiac preconditioning with sphingosine-1-phosphate requires activation of signal transducer and activator of transcription-3.

AIM: Sphingosine-1-phosphate (S1P) is a cardioprotective agent. Signal transducer and activator of transcription 3 (STAT-3) is a key mediator of many cardioprotective agents. We aimed to explore whether STAT-3 is a key mediator in S1P-induced preconditioning. METHODS: Langendorff-perfused hearts from Wistar rats and wild-type or cardiomyocyte-specific STAT-3 knockout mice were pre-treated with S1P (10 nmol/l), with or without the STAT-3 pathway inhibitor AG490, before an ischaemia-reperfusion insult. Triphenyltetrazolium chloride and Evans blue staining were used for the determination of infarct size. Western blot analysis was carried out on the S1P pre-treated hearts for detection of cytosolic, nuclear and mitochondrial phosphorylated and total STAT-3 proteins. RESULTS: Pre-treatment with S1P decreased the infarct size in isolated rat (5 ± 3% vs control 26 ± 8%, p < 0.01) and wild-type mouse hearts (13 ± 1% vs control 33 ± 3%, p < 0.05). This protective effect was abolished in the rat hearts pre-treated with AG490 (30 ± 10%, p = ns vs control) and in the hearts from STAT-3 knockout mice (35 ± 4% vs control 30 ± 3%, p = ns). Levels of phosphorylated STAT-3 were significantly increased in both the nuclear (p < 0.05 vs control) and mitochondrial (p < 0.05 vs control) fractions in the S1P pre-treated hearts, but remained unchanged in the cytosolic fraction (p = ns vs control). CONCLUSION: These novel results demonstrate that pharmacological preconditioning with S1P in the isolated heart is mediated by activation of mitochondrial and nuclear STAT-3, therefore suggesting that S1P may be a novel therapeutic target to modulate mitochondrial and nuclear function in cardiovascular disease in order to protect the heart against ischaemia-reperfusion.

Suboptimal choice in nonhuman animals: rats commit the sunk cost error.

The present experiments investigated the sunk cost error, an apparently irrational tendency to persist with an initial investment, in rats. This issue is of interest because some have argued that nonhuman animals do not commit this error. Two or three fixed-ratio (FR) response requirements were arranged on one lever, and an escape option was arranged on a second lever. The FRs were of different sizes, and escaping was the behavior of interest. Several variables that might influence the decision to persist versus escape were manipulated: the number of trials with different FR schedules in an experimental session (Exps. 1 and 2), effort to escape (Exp. 2), and the size of the larger FR (Exp. 3). The sunk cost error would result in never escaping, and the optimal strategy would be to escape from the larger FR. The main variable that determined persisting versus escaping was the size of the large FR. Rats that escaped from the large FR-apparently optimal behavior-did so at a suboptimal point, and hence committed the sunk cost error.