Behavioral Interventions to Attenuate Driven Overeating and Weight Regain After Bariatric Surgery

Weight regain after bariatric surgery is associated with problematic eating behaviors that have either recurred after a period of improvement or are new-onset behaviors. Problematic eating behaviors after bariatric surgery have been conceptualized in different ways in the literature, such as having a food addiction and experiencing a loss of control of eating. The intersection of these constructs appears to be driven overeating defined as patients’ experiences of reduced control of their eating which results in overeating behavior. The purpose of this review is to define patient experiences of driven overeating through the behavioral expression of emotion-based eating, reward-based eating, and executive functioning deficits—namely impulsivity—which is associated with weight regain after having bariatric surgery. Delineating concepts in this way and determining treatment strategies accordingly may reduce distress related to the inevitable return of increased hunger, cravings, portion sizes, and tolerance for highly palatable foods after surgery. Along with standard behavioral weight maintenance strategies, topics including acceptance, motivation, emotion-based eating, reward-based/impulsive eating, physical activity, and self-compassion are discussed. These concepts have been adapted for patients experiencing weight regain after having bariatric surgery and may be particularly helpful in attenuating driven overeating and weight regain

A Functional Near Infrared Spectroscopy (fNIRS) Replication of the Sunscreen Persuasion Paradigm

Activity in medial prefrontal cortex (mPFC) during persuasive messages predicts future message-consistent behavior change, but there are significant limitations to the types of persuasion processes that can be invoked inside an MRI scanner. For instance, real world persuasion often involves multiple people in conversation. Functional near infrared spectroscopy (fNIRS) allows us to move out of the scanner and into more ecologically valid contexts. As a first step, the current study used fNIRS to replicate an existing fMRI persuasion paradigm (i.e. the sunscreen paradigm) to determine if mPFC shows similar predictive value with this technology. Consistent with prior fMRI work, activity in mPFC was significantly associated with message-consistent behavior change, above and beyond self-reported intentions. There was also a difference in this association between previous users and non-users of sunscreen. Activity differences based on messages characteristics were not observed. Finally, activity in a region of right dorsolateral PFC (dlPFC), which has been observed with counterarguing against persuasive messages, correlated negatively with future behavior. The current results suggest it is reasonable to use fNIRS to examine persuasion paradigms that go beyond what is possible in the MRI scanner environment

Alterations in dorsal and ventral posterior cingulate connectivity in APOE ε4 carriers at risk of Alzheimer's disease

Background Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns. Aims To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele. Method Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored. Results ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity. Conclusions The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity

Inhibition of Mitochondrial Respiration as a Source of Adaphostin-induced Reactive Oxygen Species and Cytotoxicity

Adaphostin is a dihydroquinone derivative that is undergoing extensive preclinical testing as a potential anticancer drug. Previous studies have suggested that the generation of reactive oxygen species (ROS) plays a critical role in the cytotoxicity of this agent. In this study, we investigated the source of these ROS. Consistent with the known chemical properties of dihydroquinones, adaphostin simultaneously underwent oxidation to the corresponding quinone and generated ROS under aqueous conditions. Interestingly, however, this quinone was not detected in intact cells. Instead, high performance liquid chromatography demonstrated that adaphostin was concentrated by up to 300-fold in cells relative to the extracellular medium and that the highest concentration of adaphostin (3000-fold over extracellular concentrations) was detected in mitochondria. Consistent with a mitochondrial site for adaphostin action, adaphostin-induced ROS production was diminished by >75% in MOLT-4 rho(0) cells, which lack mitochondrial electron transport, relative to parental MOLT-4 cells. In addition, inhibition of oxygen consumption was observed when intact cells were treated with adaphostin. Loading of isolated mitochondria to equivalent adaphostin concentrations caused inhibition of uncoupled oxygen consumption in mitochondria incubated with the complex I substrates pyruvate and malate or the complex II substrate succinate. Further analysis demonstrated that adaphostin had no effect on pyruvate or succinate dehydrogenase activity. Instead, adaphostin inhibited reduced decylubiquinone-induced cytochrome c reduction, identifying complex III as the site of inhibition by this agent. Moreover, adaphostin enhanced the production of ROS by succinate-charged mitochondria. Collectively, these observations demonstrate that mitochondrial respiration rather than direct redox cycling of the hydroquinone moiety is a source of adaphostin-induced ROS and identify complex III as a potential target for antineoplastic agents

Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Germline Pharmacogenetic Studies

Controversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. We examined loss of heterozygosity (LOH) at the CYP2D6 locus and determined its impact on genotyping error when tumor tissue is used as a DNA source

SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis

Human African trypanosomiasis (HAT) is caused by infection with the parasite Trypanosoma brucei and is an important public health problem in sub-Saharan Africa. New, safe, and effective drugs are urgently needed to treat HAT, particularly stage 2 disease where the parasite infects the brain. Existing therapies for HAT have poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. Through an integrated drug discovery project, we have discovered and optimized a novel class of boron-containing small molecules, benzoxaboroles, to deliver SCYX-7158, an orally active preclinical drug candidate. SCYX-7158 cured mice infected with T. brucei, both in the blood and in the brain. Extensive pharmacokinetic characterization of SCYX-7158 in rodents and non-human primates supports the potential of this drug candidate for progression to IND-enabling studies in advance of clinical trials for stage 2 HAT