Randomised Clinical Trial: Calorie Restriction Regimen with Tomato Juice Supplementation Ameliorates Oxidative Stress and Preserves a Proper Immune Surveillance Modulating Mitochondrial Bioenergetics of T-Lymphocytes in Obese Children Affected by Non-Alcoholic Fatty Liver Disease (NAFLD).

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

In Vivo Biofilm Formation, Gram-Negative Infections and TAS2R38 Polymorphisms in CRSw NP Patients.

OBJECTIVES: Among the predisposing factors implicated in the immune response to airway bacterial infections, genetic variations of the bitter taste receptor TAS2R38, which is expressed in the cilia of the human sinonasal epithelial cells, seem to be associated with susceptibility to chronic rhinosinusitis (CRS) and in vitro biofilm formation. Polymorphisms in TAS2R38 generate two common haplotypes: the nonfunctional AVI (Alanine, Valine, Isoleucine) and the functional PAV (Proline, Alanine, Valine) alleles, with the latter protecting against gram-negative sinonasal infections. The aim of this study is to investigate for the first time the relevance of TAS2R38 genetic variants in the susceptibility to bacterial infections associated with in vivo biofilm formation in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. STUDY DESIGN: A prospective study on 100 adult patients undergoing functional endoscopic sinus surgery (FESS) for CRSwNP. METHODS: Propylthiouracile (PROP) testing and TAS2R38 genotyping were applied to characterize patients for receptor functionality. Sinonasal mucosa samples were processed for microbiological examination and biofilm detection. RESULTS: The nonfunctional genotype is more frequent among CRS patients than in the general population (25% vs. 18.4%, P = 0.034). Airway gram-negative infections are primarily associated with the AVI haplotype (88.9% vs. 11.1% PAV/PAV-functional genotype, P = 0.023). Biofilm formation is prevalent in CRS patients with the AVI nontaster phenotype (62.5% vs. 33.3% PAV taster or supertaster phenotype, P = 0.05). CONCLUSION: Our findings confirm an inverse correlation between TAS2R38 functionality and gram-negative infections in Italian patients with CRSwNP. In addition, for the first time we demonstrated a relationship between in vivo microbial biofilm and TAS2R38 receptor variants. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:E339-E345, 2018.

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function, efficiency, and dynamics and to an increase of OEA levels in skeletal muscle.

Is food refusal in autistic children related to TAS2R38 genotype?

Several studies suggest that atypical eating behaviors, in particular food selectivity, are more frequent in children with autism spectrum disorder (ASD). A link between bitter taste perception, namely PROP/PTC sensitivity and food preferences is known in healthy children. The aim of this study is to investigate whether genetic variants of the TAS2R38 taste receptor responsible for different bitter sensitivity could affect foods preferences and consequently food refusal in ASD children. We recruited 43 children with ASD and 41 with normotypic development (TD) with or without food selectivity, aged between 2 and 11 years. Children were characterized for bitter sensitivity by means of PROP strips and FACS analysis and genotyped for TAS2R38 polymorphisms. Food selectivity was assessed by a validated food preference questionnaire filled by parents. A statistically significant correlation between PROP sensitivity and food refusal was observed. Furthermore, a prevalence of the PAV-sensitive haplotype compared to the AVI-insensitive one was seen in ASD children with food selectivity. In agreement with the initial hypothesis the results show that food refusal in ASD children is mediated by bitter taste sensitivity thus suggesting that the bitter sensitivity test may be used as a device to orientate tailored food proposals for the practical management of food selectivity in ASD. Autism Res 2018, 11: 531-538. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A variation of the gene TAS2R38, associated with bitter taste sensitivity, can cause a different perception of some foods. In particular, some children are hypersensitive to bitterness and show a more restricted repertoire of accepted foods. We evaluate bitter sensitivity in ASD children with or without food selectivity, through a simple bitter taste test with edible strips. The results show that food refusal in ASD children can be mediated by bitter taste sensitivity thus suggesting that the bitter sensitivity test may be used as a device to orientate tailored food proposals for the practical management of food selectivity in ASD.

Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy.

BACKGROUND: The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence. METHODS: The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias. RESULTS: Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06-1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01-1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57-0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76-0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68-0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates. CONCLUSIONS: Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+.

Increased Incidence of Breast Cancer in Postmenopausal Women with High Body Mass Index at the Modena Screening Program.

PURPOSE: We conducted a study to evaluate the relationship between body mass index (BMI) and the risk of breast cancer (BC) and outcome in a population of 14,684 women aged 55 to 69 years eligible to participate in the Mammography Screening Program (MSP) in the Province of Modena, Italy. METHODS: The study population was drawn from women who underwent mammography screening between 2004 and 2006 in the Province of Modena. Women were subdivided into obese, overweight, and normal-weight categories according to BMI and followed until July 31, 2010, to evaluate the BC incidence. The clinicopathological characteristics of BC were also evaluated in different groups of patients classified according to BMI. After BC diagnosis, patients were followed for a median period of 65 (range, 2-104) months. Second events (recurrences and second tumors) were recorded, and the 5-year event-free survival (EFS) was calculated. RESULTS: After a period of 73 months, 366 cases of BC were diagnosed. Compared with normal-weight women, obese women had a significantly higher incidence of BC (relative risk [RR], 1.32; p=0.040) (RR=1), larger tumors (27% of tumors were larger than T2 size), and more nodal involvement (38.5% of tumors were node-positive). Furthermore, a significantly higher rate of total events was seen in obese women compared with overweight and normal-weight patients, respectively (17.9% vs. 11.4% vs. 10.8%, p=0.032). The 5-year EFS was 89.0%, 89.0%, and 80.0% for normal-weight, overweight, and obese patients, respectively. CONCLUSION: We observed a significantly higher risk of BC in obese women among those eligible to participate in the MSP in the Province of Modena. Finally, obese women had more second events and poorer EFS compared to nono bese women.

Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities.

Taste perception and food choices.

OBJECTIVES: The extent to which variation in taste perception influences food preferences is, to date, controversial. Bitterness in food triggers an innate aversion that is responsible for dietary restriction in children. We investigated the association among genetic variations in bitter receptor TAS2R38 and food choices in healthy children in the Mediterranean area, to develop appropriate tools to evaluate the relation among genetic predisposition, dietary habits, and feeding disorders. The aims of the study were to get a first baseline picture of taste sensitivity in healthy adults and their children and to explore taste sensitivity in a preliminary sample of obese children and in samples affected by functional gastrointestinal diseases. METHODS: Individuals (98 children, 87 parents, 120 adults) were recruited from the general population in southern Italy. Bitterness sensitivity was assessed by means of a suprathreshold method with 6-propyl-2-thiouracil. Genomic DNA from saliva was used to genotype individuals for 3 polymorphisms of TAS2R38 receptor, A49P, A262 V, and V296I. Food intake was assessed by a food frequency questionnaire. RESULTS: Children's taste sensation differed from that of adults: we observed a higher frequency of supertasters among children even in the mother-child dyads with the same diplotypes. Among adults, supertaster status was related with proline-alanine-valine (taster allele) homozygous haplotype, whereas supertaster children were mainly heterozygous. Regarding the food choices, we found that a higher percentage of taster children avoided bitter vegetables or greens altogether compared with taster adults. Taster status was also associated with body mass index in boys. CONCLUSIONS: Greater sensitivity to 6-propyl-2-thiouracil predicts lower preferences for vegetables in children, showing an appreciable effect of the genetic predisposition on food choices. None of the obese boys was a supertaster.

From the tongue to the gut.

The physiology of human taste experienced an unprecedented expansion of knowledge brought forward by modern genetics and molecular biology. In the last 10 years, the cellular organization of taste receptors from taste buds distributed in the various papillae of the tongue and the soft palate was enlightened. This molecular revolution rapidly expanded over and above the tongue because several papers reporting the presence of taste receptors in nongustatory tissues (eg, gut, brain) appeared. Hence, the issue of perception of food molecules is no longer confined to the field of nutrition and food preferences, but is rapidly expanding to gastrointestinal (GI) function and, possibly, to gut dysfunction. In children, functional GI diseases are strictly correlated to food preference and food aversion and up to now, the tools to address these kinds of problems were basic nutritional requirements, familial good sense, and a lot of patience: blunt tools to face extremely common and disturbing complaints. The fact that taste receptors are expressed down the whole of the intestinal tract is of particular interest because of their possible role in digestive behavior and absorption of nutrients; therefore, recent and future discoveries in this field will make possible the fine-tuning of new, sharper tools to treat children with functional GI diseases.

Prognosis of screen-detected breast cancers: results of a population based study.

BACKGROUND: The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15-20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP). METHODS: All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer Registry (MCR). Stage of disease and treatment information were obtained from clinical records. All the events occurring up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. RESULTS: During a 5-year period, 587 primary breast cancers were detected by the MSP and 471 primary breast cancers were diagnosed out of the MSP. The screen-detected breast cancers were smaller, more likely node negative, with low histological grade, low proliferative activity and positive receptors status. Furthermore, the breast cancer diagnosed through the MSP more frequently received a conservative surgery. The 5-year survival rate was 94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The rate of 5-year event-free survival was 89% and 75% for the MSP participants and not participants, respectively (p = 0.0001). CONCLUSIONS: Our data confirm a favourable outcome of screen-detected breast cancers in terms of five-year overall and event-free survival, which reflect the good quality assurance parameters of the MSP. Finally, a cancer registry should be implemented in every area covered by screening programs.

Changes in breast cancer incidence and stage distribution in Modena, Italy: the effect of a mammographic screening program.

OBJECTIVE: Assessing changes in breast cancer (BC) incidence and stage distribution in the District of Modena, Italy, during the period 1992-1998, and their relationship to a mammographic screening program launched in 1995. METHODS: Demographic, clinical, and pathological data of all BC cases reported to the population-based Modena Cancer Registry between 1992 and 1998 were collected and linked to the screening database. RESULTS: A total of 3429 women were diagnosed with BC in the District of Modena between 1992 and 1998. In this period the incidence rate increased by 15.7% (from 134.3 in 1992 to 155.4 per 100,000 in 1998). The increase began in 1995 and exclusively included women aged 50-69; the incidence rose by 30.4%. Moreover, the rise was confined to early tumors, with more than half (54%) of all cases reported in 1998 diagnosed as stage 0 or I disease, compared with 42% in 1992. Screen-detected tumors were significantly smaller (13.2 mm) than other tumors diagnosed in women aged 50-69 (18.5 mm), with 46% of screen-detected tumors smaller than 10 mm. Overall, a decline in the average tumor diameter was shown (from 20.2 mm in 1992-1994 to 18 mm in 1996-1998). CONCLUSIONS: Our data confirm that mammographic screening leads to an increase in the incidence of early-stage BC cancers.