CHILDHOOD OBESITY AND RELATED COMORBIDITIES:FROM UNHEALTHY DIET TO A FOOD-BASED APPROACH

The childhood obesity epidemic, that is rapidly increased in most high-income, low- and middle-income countries, is considered as one of the most serious global public health challenges for the 21st century. It may be associated with adverse health effects during childhood and an increased risk of premature morbidity and mortality later in life. Investigating possible therapeutic strategies able to counteract negative effects on child health and the risk of more severe comorbidities during adulthood is considered as a major priority. Intensive lifestyle modifications, involving diet, physical activity and behaviors are fundamental to achieve this goal. However, the characteristics of all intervention components as well as the length, the intensity, and the effectiveness of lifestyle interventions may vary largely among studies. Additionally, recently a great deal of attention has been focused on the gut microbiota as \u201cenvironmental factor\u201d playing an important role in the development of obesity and its complications and several mechanisms able to explain this association have been proposed. This evidence needs to be further elucidated because it may have a relevant role in prevention and treatment of childhood obesity. Lastly, diets high in fruits and vegetables are widely recommended for their health-promoting properties, as they are important sources of dietary fiber, vitamins, especially vitamins C and A, minerals and phytochemicals, especially antioxidants and polyphenols. It has been suggested that, among phytochemicals, salicylic acid may have an important role, being involved in the regulation of inflammation, oxidative stress and glucose metabolism. The present PhD thesis tried to further elucidate these topics through three different tasks. The primary aim of the present PhD thesis was to evaluate whether a 1-year lifestyle intervention, based on normocaloric diet, promotion of physical activity and behavior changes, may improve obesity, metabolic profile and obesity-related comorbidities, as glucose metabolism alterations, hyperlipidemia, prehypertension/hypertension, increased liver echogenicity and metabolic syndrome, in a cohort of obese children. Secondary aims were to evaluate qualitatively and quantitatively gut microbiota biodiversity in obese and normal-weight children and to compare gut microbiota profiles with SCFAs and BMI z-scores to gain insights into the structure and activity of the microbiota in pediatric obesity. The tertiary aim was to determine the concentrations of serum salicylic acid in a group of obese children, compared to normal-weight children, and to evaluate if an association may exist between serum salicylic acid and fruit and vegetable consumption. Our results confirmed that obesity is associated with detrimental effects on health already during pediatric age, thus children may show prehypertension/hypertension, insulin resistance, pre-diabetes, hyperlipidemia, liver steatosis and metabolic syndrome. Moreover, childhood obesity may be associated with changes of some core microbial species, preexisting or diet-induced, and these changes may be involved in the etiology of obesity. Among these, an alteration of the gut microbiota composition of obese children, characterized by an increased abundance of Firmicutes and a decreased abundance of Bacteroidetes, was observed. Although beneficial effects of fruit and vegetable consumption are well-known, results from our study showed that fruit and vegetable consumption in children was very low, about 50% lower of the minimum recommended value by WHO (400 g daily). Furthermore, obese children had lower levels of serum salicylic acid than normal-weight children. These results suggest that nutrition education towards an adequate fruit and vegetable consumption should be stressed in children. Moreover, although the relationship of serum salicylic acid with fruit and vegetables consumption did not reach statistical significance both in obese and normal-weight children, promotion of fruit and vegetables with higher content of salicylic acid might be considered as part of the nutrition counseling for obese children. Finally, findings from our longitudinal study clearly highlighted the importance of a 1-year lifestyle intervention, based on a normocaloric Mediterranean balanced diet for pediatric age, promotion of physical activity and behavior changes, in the improvement of cardio-metabolic risk factors and in the reduction of the prevalence of some obesity-related comorbidities, as insulin resistance, pre-diabetes, prehypertension/hypertension, hypertriglyceridemia, higher liver echogenicity and metabolic syndrome

Change in metabolic profile after 1-year nutritional-behavioral intervention in obese children

Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI), blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged 656 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-\u3b2%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI)) in BMI z-score ( 120.58 ( 120.66; 120.50)), triglycerides ( 120.35 ( 120.45; 120.25) mmol/L) and triglyceride glucose index ( 120.29 ( 120.37; 120.21)), and an increase in HDL cholesterol (0.06 (0.01; 0.11) mmol/L). Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

Clinical significance of pneumatosis intestinalis - correlation of MDCT-findings with treatment and outcome.

To evaluate the clinical significance of pneumatosis intestinalis (PI) including the influence on treatment and outcome. Two radiologists jointly reviewed MDCT-examinations of 149 consecutive emergency patients (53 women, mean age 64, range 21-95) with PI of the stomach (n = 4), small (n = 68) and/or large bowel (n = 96). PI extension, distribution and possibly associated porto-mesenteric venous gas (PMVG) were correlated with other MDCT-findings, risk factors, clinical management, laboratory, histopathology, final diagnosis and outcome. The most frequent cause of PI was intestinal ischemia (n = 80,53.7 %), followed by infection (n = 18,12.1 %), obstructive (n = 12,8.1 %) and non-obstructive (n = 10,6.7 %) bowel dilatation, unknown aetiologies (n = 8,5.4 %), drugs (n = 8,5.4 %), inflammation (n = 7,4.7 %), and others (n = 6,4 %). Neither PI distribution nor extension significantly correlated with underlying ischemia. Overall mortality was 41.6 % (n = 62), mostly related to intestinal ischemia (p = 0.003). Associated PMVG significantly correlated with underlying ischemia (p = 0.009), as did the anatomical distribution of PMVG (p = 0.015). Decreased mural contrast-enhancement was the only other MDCT-feature significantly associated with ischemia (p p &lt; 0.001). Elevated white blood count significantly correlated with ischemia (p = 0.03). In emergency patients, ischemia remains the most common aetiology of PI, showing the highest mortality. PI with associated PMVG is an alerting sign. PI together with decreased mural contrast-enhancement indicates underlying ischemia. • In emergency patients, PI may be caused by various disorders. • Intestinal ischemia remains the most common cause of PI in acute situations. • PI associated with decreased mural contrast-enhancement indicates acute intestinal ischemia. • PI associated with PMVG should alert the radiologist to possible underlying ischemia

Caenorhabditis elegans BAH-1 Is a DUF23 Protein Expressed in Seam Cells and Required for Microbial Biofilm Binding to the Cuticle

The cuticle of Caenorhabditis elegans, a complex, multi-layered extracellular matrix, is a major interface between the animal and its environment. Biofilms produced by the bacterial genus Yersinia attach to the cuticle of the worm, providing an assay for surface characteristics. A C. elegans gene required for biofilm attachment, bah-1, encodes a protein containing the domain of unknown function DUF23. The DUF23 domain is found in 61 predicted proteins in C. elegans, which can be divided into three distinct phylogenetic clades. bah-1 is expressed in seam cells, which are among the hypodermal cells that synthesize the cuticle, and is regulated by a TGF-β signaling pathway

MACI - a new era?

Full thickness articular cartilage defects have limited regenerative potential and are a significant source of pain and loss of knee function. Numerous treatment options exist, each with their own advantages and drawbacks. The goal of this review is to provide an overview of the problem of cartilage injury, a brief description of current treatment options and outcomes, and a discussion of the current principles and technique of Matrix-induced Autologous Chondrocyte Implantation (MACI). While early results of MACI have been promising, there is currently insufficient comparative and long-term outcome data to demonstrate superiority of this technique over other methods for cartilage repair