IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.

Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and whether this might associate with the severity of fatty liver disease. Secretion patterns were investigated with use of human hepatocyte, stellate, and monocyte cell lines. Associations with liver pathology were investigated in two patient cohorts: 1) biopsy-confirmed steatohepatitis and 2) class 3 obesity. We found that exposure of stellate cells to high glucose and palmitate increased IL-6 and soluble gp130 (sgp130) secretion. In line with this, plasma sgp130 in both patient cohorts positively correlated with HbA1c, and subjects with diabetes had higher circulating levels of IL-6 and trans-signaling coreceptors. Plasma sgp130 strongly correlated with liver stiffness and was significantly increased in subjects with F4 fibrosis stage. Monocyte activation was associated with reduced sIL-6R secretion. These data suggest that hyperglycemia and hyperlipidemia can directly impact IL-6 trans-signaling and that this may be linked to enhanced severity of NAFLD in patients with concomitant diabetes. ARTICLE HIGHLIGHTS: IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.

Abdominal motion tracking with free-breathing XD-GRASP acquisitions using spatio-temporal geodesic trajectories.

Free-breathing external beam radiotherapy remains challenging due to the complex elastic or irregular motion of abdominal organs, as imaging moving organs leads to the creation of motion blurring artifacts. In this paper, we propose a radial-based MRI reconstruction method from 3D free-breathing abdominal data using spatio-temporal geodesic trajectories, to quantify motion during radiotherapy. The prospective study was approved by the institutional review board and consent was obtained from all participants. A total of 25 healthy volunteers, 12 women and 13 men (38 years ± 12 [standard deviation]), and 11 liver cancer patients underwent imaging using a 3.0 T clinical MRI system. The radial acquisition based on golden-angle sparse sampling was performed using a 3D stack-of-stars gradient-echo sequence and reconstructed using a discretized piecewise spatio-temporal trajectory defined in a low-dimensional embedding, which tracks the inhale and exhale phases, allowing the separation between distinct motion phases. Liver displacement between phases as measured with the proposed radial approach based on the deformation vector fields was compared to a navigator-based approach. Images reconstructed with the proposed technique with 20 motion states and registered with the multiscale B-spline approach received on average the highest Likert scores for the overall image quality and visual SNR score 3.2 ± 0.3 (mean ± standard deviation), with liver displacement errors varying between 0.1 and 2.0 mm (mean 0.8 ± 0.6 mm). When compared to navigator-based approaches, the proposed method yields similar deformation vector field magnitudes and angle distributions, and with improved reconstruction accuracy based on mean squared errors. Schematic illustration of the proposed 4D-MRI reconstruction method based on radial golden-angle acquisitions and a respiration motion model from a manifold embedding used for motion tracking. First, data is extracted from the center of k-space using golden-angle sampling, which is then mapped onto a low-dimensional embedding, describing the relationship between neighboring samples in the breathing cycle. The trained model is then used to extract the respiratory motion signal for slice re-ordering. The process then improves the image quality through deformable image registration. Using a reference volume, the deformation vector field (DVF) of sequential motion states are extracted, followed by deformable registrations. The output is a 4DMRI which allows to visualize and quantify motion during free-breathing.

Impact of temporal resolution and motion correction for dynamic contrast-enhanced MRI of the liver using an accelerated golden-angle radial sequence.

This paper presents a prospective study evaluating the impact on image quality and quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters when varying the number of respiratory motion states when using an eXtra-Dimensional Golden-Angle Radial Sparse Parallel (XD-GRASP) MRI sequence. DCE acquisition was performed using a 3D stack-of-stars gradient-echo golden-angle radial acquisition in free-breathing with 100 spokes per motion state and temporal resolution of 6 s/volume, and using a non-rigid motion compensation to align different motion states. Parametric analysis was conducted using a dual-input single-compartment model. Nonparametric analysis was performed on the time-intensity curves. A total of 22 hepatocellular carcinomas (size: 11-52 mm) were evaluated. XD-GRASP reconstructed with increasing number of spokes for each motion state increased the signal-to-noise ratio (SNR) (p < 0.05) but decreased temporal resolution (0.04 volume/s vs 0.17 volume/s for one motion state) (p < 0.05). A visual scoring by an experienced radiologist show no change between increasing number of motion states with same number of spokes using the Likert score. The normalized maximum intensity time ratio, peak enhancement ratio and tumor arterial fraction increased with decreasing number of motion states (p < 0.05) while the transfer constant from the portal venous plasma to the surrounding tissue significantly decreased (p < 0.05). These same perfusion parameters show a significant difference in case of tumor displacement more than 1 cm (p < 0.05) whereas in the opposite case there was no significant variation. While a higher number of motion states and higher number of spokes improves SNR, the resulting lower temporal resolution can influence quantitative parameters that capture rapid signal changes. Finally, fewer displacement compensation is advantageous with lower number of motion state due to the higher temporal resolution. XD-GRASP can be used to perform quantitative perfusion measures in the liver, but the number of motion states may significantly alter some quantitative parameters.

Dynamic contrast-enhanced MRI to assess hepatocellular carcinoma response to Transarterial chemoembolization using LI-RADS criteria: A pilot study.

PURPOSE: To identify quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters indicating tumor response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). MATERIALS AND METHODS: This prospective pilot study was approved by our institutional review board; written and informed consent was obtained for each participant. Patients underwent DCE-MRI examinations before and after TACE. A variable flip-angle unenhanced 3D mDixon sequence was performed for T1 mapping. A dynamic 4D mDixon sequence was performed after contrast injection for assessing dynamic signal enhancement. Nonparametric analysis was conducted on the time-intensity curves. Parametric analysis was performed on the time-concentration curves using a dual-input single-compartment model. Treatment response according to Liver Reporting and Data System (LI-RADS) v2018 was used as the reference standard. The comparisons within groups (before vs. after treatment) and between groups (nonviable vs. equivocal or viable tumor) were performed using nonparametric bootstrap taking into account the clustering effect of lesions in patients. RESULTS: Twenty-eight patients with 52 HCCs (size: 10-104 mm) were evaluated. For nonviable tumors (n = 27), time to peak increased from 62.5 ±â€¯18.2 s before to 83.3 ±â€¯12.8 s after treatment (P< 0.01). For equivocal or viable tumors (n = 25), time to peak and mean transit time significantly increased (from 54.4 ±â€¯24.1 s to 69.5 ±â€¯18.9 s, P < 0.01 and from 14.2 ±â€¯11.8 s to 33.9 ±â€¯36.8 s, P= 0.01, respectively) and the transfer constant from the extracellular and extravascular space to the central vein significantly decreased from 14.8 ±â€¯14.1 to 8.1 ±â€¯9.1 s-1 after treatment (P= 0.01). CONCLUSION: This prospective pilot DCE-MRI study showed that time to peak significantly changed after TACE treatment for both groups (nonviable tumors and equivocal or viable tumors). In our cohort, several perfusion parameters may provide an objective marker for differentiation of treatment response after TACE in HCC patients.

Food insecurity and food consumption by season in households with children in an Arctic city: a cross-sectional study.

BACKGROUND: High rates of food insecurity are documented among Inuit households in Canada; however, data on food insecurity prevalence and seasonality for Inuit households with children are lacking, especially in city centres. This project: (1) compared food consumption patterns for households with and without children, (2) compared the prevalence of food insecurity for households with and without children, (3) compared food consumption patterns and food insecurity prevalence between seasons, and (4) identified factors associated with food insecurity in households with children in Iqaluit, Nunavut, Canada. METHODS: Randomly selected households were surveyed in Iqaluit in September 2012 and May 2013. Household food security status was determined using an adapted United States Department of Agriculture Household Food Security Survey Module. Univariable logistic regressions were used to examine unconditional associations between food security status and demographics, socioeconomics, frequency of food consumption, and method of food preparation in households with children by season. RESULTS: Households with children (n = 431) and without children (n = 468) participated in the survey. Food insecurity was identified in 32.9% (95% CI: 28.5-37.4%) of households with children; this was significantly higher than in households without children (23.2%, 95% CI: 19.4-27.1%). The prevalence of household food insecurity did not significantly differ by season. Demographic and socioeconomic characteristics of the person responsible for food preparation, including low formal education attainment (ORSept = 4.3, 95% CI: 2.3-8.0; ORMay = 3.2, 95% CI: 1.8-5.8), unemployment (ORSept = 1.1, 95% CI: 1.1-1.3; ORMay = 1.3, 95% CI: 1.1-1.5), and Inuit identity (ORSept = 8.9, 95% CI: 3.4-23.5; ORMay = 21.8, 95% CI: 6.6-72.4), were associated with increased odds of food insecurity in households with children. Fruit and vegetable consumption (ORSept = 0.4, 95% CI: 0.2-0.8; ORMay = 0.5, 95% CI: 0.2-0.9), as well as eating cooked (ORSept = 0.5, 95% CI: 0.3-1.0; ORMay = 0.5, 95% CI: 0.3-0.9) and raw (ORSept = 1.7, 95% CI: 0.9-3.0; ORMay = 1.8, 95% CI: 1.0-3.1) fish were associated with decreased odds of food insecurity among households with children, while eating frozen meat and/or fish (ORSept = 2.6, 95% CI: 1.4-5.0; ORMay = 2.0, 95% CI: 1.1-3.7) was associated with increased odds of food insecurity. CONCLUSIONS: Food insecurity is high among households with children in Iqaluit. Despite the partial subsistence livelihoods of many Inuit in the city, we found no seasonal differences in food security and food consumption for households with children. Interventions aiming to decrease food insecurity in these households should consider food consumption habits, and the reported demographic and socioeconomic determinants of food insecurity.

Community-based adaptation research in the Canadian Arctic.

Community-based adaptation (CBA) has emerged over the last decade as an approach to empowering communities to plan for and cope with the impacts of climate change. While such approaches have been widely advocated, few have critically examined the tensions and challenges that CBA brings. Responding to this gap, this article critically examines the use of CBA approaches with Inuit communities in Canada. We suggest that CBA holds significant promise to make adaptation research more democratic and responsive to local needs, providing a basis for developing locally appropriate adaptations based on local/indigenous and Western knowledge. Yet, we argue that CBA is not a panacea, and its common portrayal as such obscures its limitations, nuances, and challenges. Indeed, if uncritically adopted, CBA can potentially lead to maladaptation, may be inappropriate in some instances, can legitimize outside intervention and control, and may further marginalize communities. We identify responsibilities for researchers engaging in CBA work to manage these challenges, emphasizing the centrality of how knowledge is generated, the need for project flexibility and openness to change, and the importance of ensuring partnerships between researchers and communities are transparent. Researchers also need to be realistic about what CBA can achieve, and should not assume that research has a positive role to play in community adaptation just because it utilizes participatory approaches. WIREs Clim Change 2016, 7:175-191. doi: 10.1002/wcc.376 For further resources related to this article, please visit the WIREs website.

Food policy in the Canadian North: Is there a role for country food markets?

Food insecurity is widely reported to be at a crisis level in the Inuit territory of Nunavut, Canada. Various policies, programs, and initiatives have been proposed to tackle the problem, with increasing interest in developing a system of country food markets (CFMs) similar to Greenland. We examine if CFMs offer a feasible, sustainable, and effective model for strengthening food systems in Nunavut, examining the model of Greenland and drawing on semi-structured interviews with key informants (n = 45). The Greenland experience indicates that CFMs can provide access to sufficient, safe, and nutritious food on a regular basis, and can diversify locally available foods. These benefits are transferable to Nunavut, although knowledge gaps, regulatory and institutional conditions, and concerns over how CFMs might affect the cultural basis of food systems, underlies apprehension over their development in the territory. We conclude that Nunavut is not currently in the position to develop CFMs, but the role of such markets in potentially strengthening food systems should not be discounted. Future development would need to solicit community input on CFMs, resolve regulatory issues around wildlife management and harvesting, and study how future risks would affect sustainability and effectiveness.

The prevalence of food insecurity is high and the diet quality poor in Inuit communities.

Indigenous peoples experience a disproportionate burden of food insecurity and the Arctic is no exception. We therefore evaluated the prevalence, socio-demographic, and dietary correlates of food insecurity in the most comprehensive assessment of food insecurity in Arctic Canada. A cross-sectional survey of 1901 Inuit households was conducted in 2007-2008. Measurements included food insecurity, 24-h dietary recalls, socio-demographics, and anthropometry. Food insecurity was identified in 62.6% of households (95% CI = 60.3-64.9%) with 27.2% (95% CI = 25.1-29.3%) of households severely food insecure. The percent with an elevated BMI, waist circumference, and percent body fat was lower among individuals from food insecure households compared to food secure households (P ≤ 0.001). Adults from food insecure households had a significantly lower Healthy Eating Index score and consumed fewer vegetables and fruit, grains, and dairy products, and consumed a greater percent of energy from high-sugar foods than adults from food secure households (P ≤ 0.05). Food insecurity was associated with household crowding, income support, public housing, single adult households, and having a home in need of major repairs (P ≤ 0.05). The prevalence of having an active hunter in the home was lower in food insecure compared to food secure households (P ≤ 0.05). Food insecurity prevalence is high in Inuit communities, with implications for diet quality that over the long-term would be anticipated to exacerbate the risk of diet-related chronic diseases. Actions are required to improve food security that incorporate the traditional food system and healthy market food choices.

Prevalence of affirmative responses to questions of food insecurity: International Polar Year Inuit Health Survey, 2007-2008.

OBJECTIVES: Assess the prevalence of food insecurity by region among Inuit households in the Canadian Arctic. STUDY DESIGN: A community-participatory, cross-sectional Inuit health survey conducted through face-to-face interviews. METHODS: A quantitative household food security questionnaire was conducted with a random sample of 2,595 self-identified Inuit adults aged 18 years and older, from 36 communities located in 3 jurisdictions (Inuvialuit Settlement Region; Nunavut; Nunatsiavut Region) during the period from 2007 to 2008. Weighted prevalence of levels of adult and household food insecurity was calculated. RESULTS: Differences in the prevalence of household food insecurity were noted by region, with Nunavut having the highest prevalence of food insecurity (68.8%), significantly higher than that observed in Inuvialuit Settlement Region (43.3%) and Nunatsiavut Region (45.7%) (p≤0.01). Adults living in households rated as severely food insecure reported times in the past year when they or other adults in the household had skipped meals (88.6%), gone hungry (76.9%) or not eaten for a whole day (58.2%). Adults living in households rated as moderately food insecure reported times in the past year when they worried that food would run out (86.5%) and when the food did not last and there was no money to buy more (87.8%). CONCLUSIONS: A high level of food insecurity was reported among Inuit adults residing in the Canadian Arctic, particularly for Nunavut. Immediate action and meaningful interventions are needed to mitigate the negative health impacts of food insecurity and ensure a healthy Inuit population.

Emotional reinforcement as a protective factor for healthy eating in home settings.

BACKGROUND: According to the literature, meals consumed at home are healthier than those consumed away from home (AFH), but reasons underlying this protective effect have not been fully understood. Emotional reinforcement of healthy eating patterns at home is examined as a putative contributing mechanism. OBJECTIVE: This study examined expectations for within-individual emotional reinforcement of healthy eating at home, reflected in reports of 1) more intense positive and less intense negative affects after healthier meals than at baseline at home (and not in AFH settings) and 2) more intense positive and less intense negative affects reported before a meal being predictive of healthier meals than at baseline at home (and not in AFH settings). DESIGN: A total of 160 nonobese women reported their eating behavior and momentary emotional states every 2 h, 6 times/d over 10 observation days. We examined observations with meals (breakfast, lunch, or dinner). The participants indicated how momentary eating patterns compared with their own baseline eating patterns (healthier, equal, or less healthy). Concurrent (after meal) and lagged (before meal) emotion scores were specified. RESULTS: At-home meals were followed by more intense positive emotions and less worry than were AFH meals. As expected, home meals that were healthier than a person's baseline meals were followed by more intense positive emotions, with a relation of opposite direction being observed in AFH settings. At home, more intense premeal positive emotions cued healthier next-meal eating patterns than did those at baseline, with no such relation being observed in AFH settings. CONCLUSION: The home is a privileged environment that nurtures healthy eating and in which healthier food choices trigger and are triggered by more positive emotions.

Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000.

OBJECTIVE: To describe the clinical and biologic evolution of HIV-1 infection in Africa. METHODS: One hundred four HIV-1-infected individuals were identified prospectively from regular blood donors in Abidjan, Côte d'Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical follow-up was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. RESULTS: The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4 + cell count was 527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and 95% of the patients received primary prophylaxis with co-trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B-defining event. The 3-year AIDS-free and symptom-free probabilities were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5-87.2), respectively. During the first 3 years of follow-up, we observed that the median plasma viral load stabilized at >4 log 10 copies/ml and that the median CD4 + cell count declined by 20 to 25/mm 3 per year. CONCLUSION: These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events.