Search

Similarities in neural activation patterns in obese and substance-dependent subjects led to the food addiction concept, but studies exploiting this issue for obesity stratification are missing. We assessed brain activation in response to food cues using 18 F-2-fluoro-2-deoxy-glucose-PET in 36 overweight women, stratified by low or high food addiction groups according to the Yale Food Addiction Scale (YFAS). Assessments were repeated after a 3-month diet. We found greater activation in thalamus, hypothalamus, midbrain, putamen, and occipital cortex (reward), but not in prefrontal and orbitofrontal cortices (control/reward receipt) in the high-YFAS versus low-YFAS group. In high-YFAS subjects, orbitofrontal responsiveness was inversely related to YFAS severity and hunger rating, and positive associations were observed between regional brain activation and lipid intake. A 3-month diet abolished group differences in brain activation. Our data suggest that food addiction distinguishes an overweight phenotype that can be reversed by diet, opening to personalized strategies in obesity treatment., (© 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Background and Purpose: In contrast with the carotid arteries, the vertebral arteries (VAs) show considerable variation in length, caliber, and vessel course. This study investigated whether the variation in diameter and flow characteristics of the VAs might be inherited., Methods: A total of 172 Italian twins from Padua, Perugia, and Terni (54 monozygotic, 32 dizygotic) recruited from the Italian Twin Registry underwent B-mode and pulsed-wave Doppler ultrasound assessment of their VAs. VA diameters, peak systolic velocity (PSV) and end diastolic velocity (EDV) were assessed at the level of a horizontal V2 segment. Univariate quantitative genetic modeling was performed., Results: Fourteen percent of the sample had VA hypoplasia. Within pair correlation in monozygotic twins was higher than in dizygotics (.552 vs. .229) for VA diameter. Age- and sex-adjusted genetic effect, under the most parsimonious model, accounted for 54.7% (95% CI: 42.2-69.1%) of the variance of VA diameter, and unshared environmental effect for 45.3% (95% CI: 30.9-57.8%). No heritability was found for the PSV of VA, but shared (34.1%; 95% CI: 16.7-53.7%) and unshared (65.9%; 95% CI: 45.9-83.1%) environmental factors determined the variance. EDV of VA is moderately genetically influenced (42.4%; 95% CI: 16.1-64.9%) and also determined by the unshared environment (57.6%; 95% CI: 34.7-83.7%)., Conclusions: The diameter of the VAs is moderately genetically determined. Different factors influence the PSV and EDV of VAs, which may highlight the complex hemodynamic background of VA flow and help to understand the vertebral flow anomalies found by ultrasound., (Copyright © 2017 by the American Society of Neuroimaging.)

Background: Temporary placement of removable, fully covered, self-expandable metal stents (fcSEMS) for treatment of benign biliary strictures (BBS) has been reported to be effective. However, the optimal extraction time point remains unclear and stent migration has been a major concern., Objective: The objective of this study was to evaluate the efficacy and safety of this treatment modality using an fcSEMS with a special antimigration design and prolonged stent indwell time., Methods: We performed a prospective, single-arm study at six tertiary care centers in Europe. Patients with BBS underwent endoscopic or percutaneous implantation of an fcSEMS (GORE® VIABIL® Biliary Endoprosthesis, W.L. Gore & Associates, Flagstaff, AZ, USA). The devices were scheduled to be removed nine months later, and patients were to return for follow-up for an additional 15 months., Results: Forty-three patients were enrolled in the study. Stricture etiology was chronic pancreatitis in the majority of patients (57.5%). All fcSEMS were placed successfully, either endoscopically (76.7%) or percutaneously (23.3%). Stent migration was observed in two patients (5.2%). Primary patency of the SEMS prior to removal was 73.0%. All attempted stent removals were successful. At removal, stricture was resolved or significantly improved without need for further therapy in 78.9% of patients. Stricture recurrence during a follow-up of two years post-implant was observed in two patients., Conclusions: Temporary placement of the fcSEMS is a feasible, safe and effective treatment for BBS. The design of the device used in this study accounts for very low migration rates and facilitates easy stent retrieval, even after it has been in place for up to 11 months.

Malnutrition increases the risk of infections in patients receiving medical and surgical procedures, but it is not clear whether it may facilitate also the development of opportunistic infections in human immunodeficiency virus (HIV)-negative patients not receiving immunosuppressive therapies. Here we report the first case of a non-HIV, severely malnourished woman who developed Pneumocystis jirovecii pneumonia. This report highlights the clinical relevance of malnutrition as a determinant of immune suppression, which in turn may also favor opportunistic infections. Therefore, routine nutrition screening and assessment, as well as timely start of nutrition therapy, should be prioritized in daily clinical practice to reduce complications and improve outcome., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Brain plasticity is the basis for systems-level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25-minutes of task practice, were performed. Within-session between-run change in task-related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients' sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium-enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between-run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice-induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short-term plasticity underlying motor practice. Reduction of inflammation with IFN beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery-oriented strategies that rely on patients' brain plasticity. Hum Brain Mapp 37:2431-2445, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Wordom is a versatile, user-friendly, and efficient program for manipulation and analysis of molecular structures and dynamics. The following new analysis modules have been added since the publication of the original Wordom paper in 2007: assignment of secondary structure, calculation of solvent accessible surfaces, elastic network model, motion cross correlations, protein structure network, shortest intra-molecular and inter-molecular communication paths, kinetic grouping analysis, and calculation of mincut-based free energy profiles. In addition, an interface with the Python scripting language has been built and the overall performance and user accessibility enhanced. The source code of Wordom (in the C programming language) as well as documentation for usage and further development are available as an open source package under the GNU General Purpose License from http://wordom.sf.net., (Copyright © 2010 Wiley Periodicals, Inc.)

Background: Reduced circulating and tissue carnitine levels, possibly leading to impaired mitochondrial function, have been postulated to be involved in the pathogenesis of insulin resistance. However, whether L-carnitine administration may improve insulin sensitivity in patients with impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM-2) is still controversial. The aim of the study was to explore the role of L-carnitine supplementation in influencing insulin sensitivity., Methods: A randomized controlled study involving adult outpatients was designed. Adult patients referred to the outpatient clinic and within 10 days of the diagnosis of IFG or DM-2 were consecutively enrolled. Exclusion criteria were concomitant antidiabetic therapy and modifications of lifestyle during the previous 4 weeks. Patients were randomly assigned to receive a hypocaloric diet for 10 days (group C; n = 8) or the same dietetic regimen in addition to oral L-carnitine (2 g twice daily) supplementation (group LC; n = 8). Oral glucose tolerance test (OGTT), fasting plasma insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at the beginning and end of the study. Data were statistically analyzed using the Student t test for paired and unpaired data., Results: OGTT at 2 hours improved in both groups. Only in the L-carnitine-supplemented group did plasma insulin levels and HOMA-IR significantly decrease when compared to baseline values., Conclusions: Considering the role of caloric restriction in increasing the intestinal uptake of carnitine, the results suggest that oral L-carnitine administration, when associated with a hypocaloric feeding regimen, improves insulin resistance and may represent an adjunctive treatment for IFG and DM-2.

Background: Tumour necrosis factor-alpha (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results., Materials and Methods: We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation., Results: TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64.3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53.6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32.1%) at 20.00 h. Mean TNF levels were 14.3 +/- 4 pg mL(-1) at 08.00 h, 16.7 +/- 4.6 pg mL(-1) at 14.00 h (P = 0.05) and 18.5 +/- 10.2 pg mL(-1) at 20.00 h (P < 0.05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient = - 0.420; P = 0.026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26.3 +/- 8.3, 8.9 +/- 4.2, 3.8 +/- 2.1, respectively; P = 0.04 at one-way ANOVA). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant., Conclusions: The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss.

Objective: Increased brain tryptophan (TRP) availability for serotonin synthesis may play a role in the pathogenesis of anorexia. Since in chronic liver failure, increased plasma and cerebrospinal fluid TRP concentrations are characteristically reported, we hypothesize that also in liver cirrhosis increased brain TRP availability may constitute the pathogenic mechanism of anorexia. To test this hypothesis, the association between anorexia and plasma TRP was investigated., Methods: Anorexia and plasma amino acid concentrations were evaluated in 16 patients with liver cirrhosis and compared with those obtained in 13 healthy volunteers., Results: According to a questionnaire, 11 cirrhotic patients were considered as anorectic. In these patients, brain TRP availability was significantly higher than in nonanorectic patients and controls., Discussion: Increased brain TRP availability is also associated with anorexia in liver cirrhosis, and supports the hypothesis that increased serotonergic activity may constitute the common pathogenic mechanism for anorexia associated with different diseases.

Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10(6) methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17-18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor-associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia.

Impairment of the nutritional state plays a major role in the morbidity and mortality of cancer patients. However, the opportunity of providing artificial nutritional support to these patients is still debated, because of the concern that energy substrates administered to replete the host may concomitantly stimulate tumor growth. A correct nutritional approach to cancer patients should thus be based on a thorough knowledge of both host and tumor metabolic needs and host-tumor metabolic interactions. Specific modifications of plasma levels of glucogenic, aromatic, sulfur-containing and branched-chain amino acids have been demonstrated in cancer patients, indicating a specific influence of the tumor on amino acid metabolism. Little is known about protein metabolism in neoplastic tissue. Interference with tumor growth has been attempted by deprivation of single amino acids with controversial results. Increased gluconeogenesis and insulin resistance are responsible for the two main abnormalities in carbohydrate metabolism in cancer patients, namely increased glucose turnover and impaired glucose tissue disposal. Lipid metabolism is also affected by the neoplasm: soluble factors such as "lipid-mobilizing factor" lead to increased fat mobilization from adipose tissue; plasma elimination of exogenous triglycerides has also been found to be reduced probably because of a tumor-related decrease in lipoprotein lipase activity. The differences in glucose and fat utilization between tumor and host should be considered in the nutritional approach to cancer patients. Data in this respect are controversial and have been obtained only in experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial and internal jugular venous levels of false neurotransmitters (FNTs: octopamine, OCT, and phenylethanolamine, PEA), aromatic and branched-chain amino acids, glutamine, ammonia, and pH were measured in patients with portal-systemic encephalopathy (PSE) and in appropriate controls to define the role of these parameters in the pathogenesis of hepatic coma. The typical plasma patterns reported in the literature were observed: hyperammonaemia (59 +/- 8 mumol/l v. controls 30 +/- 4, P less than 0.005), elevated OCT (19 +/- 3 nmol/l v. 6 +/- 1, P less than 0.001) and PEA (64 +/- 8 nmol/l v. 27 +/-3, P less than 0.001), high ratio of aromatic to branched-chain amino acids (0.92 +/- 0.12 v. 0.32 +/- 0.04, P less than 0.005), and variable glutamine levels 216-734 mumol/l). No consistent net flux into or out of the brain could be demonstrated for any of these substances. The degree of encephalopathy correlated with the level of respiratory alkalosis (r=0.325, P less than 0.05) which, in turn, correlated with the degree of elevation of plasma OCT (r=0.439, P less than 0.05) and PEA (r=0.489, P less than 0.05) as well as with the excess of glutamine efflux from the brain (r=0.927, P less than 0.05). These findings support current views that hyperammonaemia, plasma amino acid imbalance, and elevated production of FNTs are interrelated disturbances which contribute to the pathogenesis of PSE. In addition, the data suggest that alkalosis accentuates the altered metabolism of these substances within the brain.

The characteristic amino acid pattern observed in chronic liver failure with high aromatic and low branched chain amino acid levels is considered to be consequent to increased muscle protein catabolism. The main catabolic stimulus has been attributed to hyperglucagonemia and to a reduced insulin/glucagon molar ratio. Intravenous administration of a solution containing branched chain amino acids and glucose to patients with chronic liver cirrhosis rapidly normalizes the plasma amino acid pattern. This effect may result from either a change in the insulin/glucagon ratio, induced by glucose, or from the anticatabolic influence of branched chain amino acids on muscle protein turnover. To discriminate between these two possibilities, a crossover study was carried out to determine the effect of a 24-hour infusion of either glucose alone, or glucose plus branched chain amino acids, in seven patients with chronic liver failure. Blood glucose, insulin, glucagon, free fatty acids, and amino acid levels were determined. Branched chain amino acids were much more effective than glucose (p less than 0.01) in decreasing the levels of aromatic amino acids. Conversely, the insulin, glucagon, and free fatty acid levels with glucose alone were not altered with the addition of branched chain amino acids. These findings suggest an anticatabolic effect of branched chain amino acids on muscle protein turnover and suggest that factors other than insulin and glucagon may be responsible for the characteristic plasma amino acid pattern present in chronic liver failure.

The tolerance to exogenous fats has been evaluated in patients with liver cirrhosis. A three-stage lipid clearance test with continuous infusion (3 hr) of a triglyceride emulsion, Intralipid, was performed on 10 patients with well compensated liver cirrhosis and 10 normolipidemic volunteers. During the infusion, blood samples were collected for the measurement of particulate triglycerides (TG) by nephelometry; samples were also collected for total TG, free fatty acids (FFA) and free tryptophan (TRP) determinations. Plasma endogenous triglycerides were calculated as the total minus exogenous, particulate, TG. The fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous TG were lower in patients than in controls, though a significant difference (p less than 0.05) was found only for K1. Endogenous TG and FFA showed a comparable rise in patients and controls during Intralipid infusion. A significant increase in free TRP was noted in cirrhotics upon maximal infusion rate. It is concluded that: in patients with well compensated liver cirrhosis the maximal clearing capacity (K1) for exogenous TG is impaired. Nonetheless, moderate amounts of fat may be removed at a normal rate from the bloodstream; a normal synthesis rate of exogenous TG may be maintained even in a severely damaged liver; considering the possible role of free TRP in the pathogenesis of hepatic encephalopathy (HE), the use of large amounts of lipids should be discouraged in patients with decompensated liver cirrhosis, or even avoided in those with impending or overt HE.