A walnut-containing meal had similar effects on early satiety, CCK, and PYY, but attenuated the postprandial GLP-1 and insulin response compared to a nut-free control meal.

Regular nut consumption is associated with lower adiposity and reduced weight gain in adulthood. Walnut feeding studies have observed minimal effect on body weight despite potential additional energy intake. Several mechanisms may explain why consuming nuts promotes weight control, including increased early phase satiety, possibly reflected in postprandial response of gastrointestinal and pancreatic peptides hypothesized to affect appetite. The purpose of this study was to compare postprandial insulin, glucagon and gastrointestinal peptide response and satiety following a meal with ∼54% of energy from walnuts or cream cheese, using a within-subject crossover study design in overweight/obese adults (N = 28). Sixty minutes after the walnut-containing meal, glucagon-like peptide-1 was lower than after the reference meal (p=0.0433), and peptide YY, cholecystokinin and ghrelin did not differ after the two meals. Sixty and 120 min after the walnut-containing meal, pancreatic polypeptide (p = 0.0014 and p = 0.0002) and glucose-dependent insulinotropic peptide (p < 0.0001 and p = 0.0079) were lower than after the reference meal, and 120 min after the walnut-containing meal, glucagon was higher (p=0.0069). Insulin and C-peptide increased at 60 min in response to both meals but were lower at 120 min after the walnut-containing meal (p=0.0349 and 0.0237, respectively). Satiety measures were similar after both meals. These findings fail to support the hypothesis that acute postprandial gastrointestinal peptide response to a walnut-containing meal contributes to increased satiety. However, inclusion of walnuts attenuated the postprandial insulin response, which may contribute to the more favorable lipid profile observed in association with regular walnut consumption

The IL-6 Gene Promoter SNP and Plasma IL-6 in Response to Diet Intervention.

We recently reported that interleukin-6 (IL-6), an inflammatory marker associated with breast pathology and the development of breast cancer, decreases with diet intervention and weight loss in both insulin-sensitive and insulin-resistant obese women. Here, we tested whether an individual's genotype at an IL6 SNP, rs1800795, which has previously been associated with circulating IL-6 levels, contributes to changes in IL-6 levels or modifies the effect of diet composition on IL-6 in these women. We genotyped rs1800795 in overweight/obese women (N = 242) who were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet in a 1-year weight loss intervention study of obesity-related biomarkers for breast cancer incidence and mortality. Plasma IL-6 levels were measured at baseline, 6 and 12 months. At baseline, individuals with a CC genotype had significantly lower IL-6 levels than individuals with either a GC or GG genotype (p < 0.03; 2.72 pg/mL vs. 2.04 pg/mL), but this result was not significant when body mass index (BMI) was accounted for; the CC genotype group had lower BMI (p = 0.03; 32.5 kg/m² vs. 33.6 kg/m²). We did not observe a 2-way interaction of time*rs1800795 genotype or diet*rs1800795 genotype. Our findings provide evidence that rs1800795 is associated with IL-6 levels, but do not support a differential interaction effect of rs1800795 and diet composition or time on changes in circulating IL-6 levels. Diet intervention and weight loss are an important strategy for reducing plasma IL-6, a risk factor of breast cancer in women, regardless of their rs1800795 genotype

Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women.

BackgroundOptimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses.Methods and resultsOverweight and obese women (n=245) were enrolled in a 1-year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut-rich diet increased high-density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut-rich diet also reduced low-density lipoprotein cholesterol in insulin-sensitive women, whereas the lower fat diet reduced both total cholesterol and high-density lipoprotein cholesterol in insulin-sensitive women (P<0.05). Insulin sensitivity and C-reactive protein levels also improved.ConclusionsWeight loss was similar across the diet groups, although insulin-sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut-rich, higher fat diet resulted in the most favorable changes in lipid levels.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01424007

Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation

Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell\u27s expressed genes and then transport and display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological cells that are synthesizing abnormal proteins, such as cancers that are expressing mutated proteins. In order for many cancers to arise and progress, they need to evolve mechanisms to avoid elimination by CD8 T cells. MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Here we review the evidence that loss of MHC I antigen presentation is a frequent occurrence in many cancers. We discuss new insights into some common underlying mechanisms through which some cancers inactivate the MHC I pathway and consider some possible strategies to overcome this limitation in ways that could restore immune control of tumors and improve immunotherapy

Weight loss, glycemic control, and cardiovascular disease risk factors in response to differential diet composition in a weight loss program in type 2 diabetes: a randomized controlled trial.

ObjectiveTo test whether a weight loss program promotes greater weight loss, glycemic control, and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake.Research design and methodsThis randomized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling, with prepackaged foods in a planned menu during the initial phase, or to usual care (UC; two weight loss counseling sessions and monthly contacts).ResultsRelative weight loss was 7.4% (95% CI 5.7-9.2%), 9.0% (7.1-10.9%), and 2.5% (1.3-3.8%) for the lower fat, lower carbohydrate, and UC groups (P < 0.001 intervention effect). Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year (fasting glucose 141 [95% CI 133-149] vs. 159 [144-174] mg/dL, P = 0.023; hemoglobin A1c 6.9% [6.6-7.1%] vs. 7.5% [7.1-7.9%] or 52 [49-54] vs. 58 [54-63] mmol/mol, P = 0.001; triglycerides 148 [134-163] vs. 204 [173-234] mg/dL, P < 0.001). The lower versus higher carbohydrate groups maintained lower hemoglobin A1c (6.6% [95% CI 6.3-6.8%] vs. 7.2% [6.8-7.5%] or 49 [45-51] vs. 55 [51-58] mmol/mol) at 1 year (P = 0.008).ConclusionsThe weight loss program resulted in greater weight loss and improved glycemic control in type 2 diabetes

Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted

Tumour Suppressor Genes with Oncogenic Roles in Lung Cancer

Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. High-throughput sequencing efforts have uncovered the molecular heterogeneity of this disease, unveiling several genetic and epigenetic disruptions driving its development. Unlike oncogenes, tumour suppressor genes negatively regulate cell cycle control and exhibit loss-of-function alterations in cancer. Although tumour suppressor genes are more frequently disrupted, oncogenes are more likely to be drug-targeted. Many genes are described as presenting both tumour suppressive and oncogenic functions in different tumour types or even within the natural history of the disease in a single tumour. In this chapter, we describe current knowledge of tumour suppressor genes in lung tissues, focusing on tumour suppressor/oncogene duality

Detection of explosive events by monitoring acoustically-induced geomagnetic perturbations

The Black Thunder Coal Mine (BTCM) near Gillette, Wyoming was used as a test bed to determine the feasibility of detecting explosion-induced geomagnetic disturbances with ground-based induction magnetometers. Two magnetic observatories were fielded at distances of 50 km and 64 km geomagnetically north from the northernmost edge of BTCM. Each observatory consisted of three separate but mutually orthogonal magnetometers, Global Positioning System (GPS) timing, battery and solar power, a data acquisition and storage system, and a three-axis seismometer. Explosions with yields of 1 to 3 kT of TNT equivalent occur approximately every three weeks at BTCM. We hypothesize that explosion-induced acoustic waves propagate upward and interact collisionally with the ionosphere to produce ionospheric electron density (and concomitant current density) perturbations which act as sources for geomagnetic disturbances. These disturbances propagate through an ionospheric Alfven waveguide that we postulate to be leaky (due to the imperfectly conducting lower ionospheric boundary). Consequently, wave energy may be observed on the ground. We observed transient pulses, known as Q-bursts, with pulse widths about 0.5 s and with spectral energy dominated by the Schumann resonances. These resonances appear to be excited in the earth-ionosphere cavity by Alfven solitons that may have been generated by the explosion-induced acoustic waves reaching the ionospheric E and F regions and that subsequently propagate down through the ionosphere to the atmosphere. In addition, we observe late time (> 800 s) ultra low frequency (ULF) geomagnetic perturbations that appear to originate in the upper F region ({approximately}300 km) and appear to be caused by the explosion-induced acoustic wave interacting with that part of the ionosphere. We suggest that explosion-induced Q-bursts may be discriminated from naturally occurring Q-bursts by association of the former with the late time explosion-induced ULF perturbations. We also present evidence for an acoustically-induced magnetic signal at both magnetic observatories, indicating that magnetometers act as highly sensitive detectors of acoustically-induced ground motion. Further experimental and theoretical work are required to improve confidence in these conclusions

Ambiguous figures and the content of experience

Representationalism is the position that the phenomenal character of an experience is either identical with, or supervenes on, the content of that experience. Many representationalists hold that the relevant content of experience is nonconceptual. I propose a counterexample to this form of representationalism that arises from the phenomenon of Gestalt switching, which occurs when viewing ambiguous figures. First, I argue that one does not need to appeal to the conceptual content of experience or to judgements to account for Gestalt switching. I then argue that experiences of certain ambiguous figures are problematic because they have different phenomenal characters but that no difference in the nonconceptual content of these experiences can be identified. I consider three solutions to this problem that have been proposed by both philosophers and psychologists and conclude that none can account for all the ambiguous figures that pose the problem. I conclude that the onus is on representationalists to specify the relevant difference in content or to abandon their position