Fetal-Maternal Exposure to Endocrine Disruptors: Correlation with Diet Intake and Pregnancy Outcomes

Endocrine-disrupting chemicals (EDCs) are exogenous substances able to mimic or to interfere with the endocrine system, thus altering key biological processes such as organ development, reproduction, immunity, metabolism and behavior. High concentrations of EDCs are found in several everyday products including plastic bottles and food containers and they could be easily absorbed by dietary intake. In recent years, considerable interest has been raised regarding the biological effects of EDCs, particularly Bisphenol A (BPA) and phthalates, on human pregnancy and fetal development. Several evidence obtained on in vitro and animal models as well as by epidemiologic and population studies strongly indicated that endocrine disruptors could negatively impact fetal and placental health by interfering with the embryonic developing epigenome, thus establishing disease paths into adulthood. Moreover, EDCs could cause and/or contribute to the onset of severe gestational conditions as Preeclampsia (PE), Fetal Growth Restriction (FGR) and gestational diabetes in pregnancy, as well as obesity, diabetes and cardiovascular complications in reproductive age. Therefore, despite contrasting data being present in the literature, endocrine disruptors must be considered as a therapeutic target. Future actions aimed at reducing or eliminating EDC exposure during the perinatal period are mandatory to guarantee pregnancy success and preserve fetal and adult health

3D stereophotogrammetric facial analysis of SMAII patients

Spinal muscular atrophy (SMA) is a rare neurodegenerative disease, due to autosomal recessive mutations on SMN1 gene. It is clinically classified into 4 phenotypes (SMAI-SMAIV) and it is characterized by muscular weakness and atrophy of the voluntary muscles of the legs, arms and trunk [1]. No information is available about soft tissue facial characteristics in these patients. To better define their facial phenotype and to evidence possible modifications, the 3D facial reconstructions of 12 male SMAII patients (3-8 years) were evaluated. All of them were able to sit, but not to walk independently and had respiratory problems, chewing and swallowing difficulties. The facial reconstructions were obtained through a stereophotogrammetric system, after the non-invasive identification of 50 facial reference landmarks, whose 3D coordinates were used to calculate a series of linear measurements. Data were compared with those of healthy controls, matched for age and sex, through the calculation of z-score values [2]. Results show that patients have larger skull base, mandibular and facial widths (z-score = 1.5, 2 and 1.8 respectively), together with an increased height of the nose (z-score = 3) and mandibular body length (z-score = 2.1). The mandibular ramus length is reduced (z-score = -2.6). Results are of interest to define the facial anatomy of these patients, since a detailed knowledge of their facial features can be useful to create ergonomic devices, as respiratory masks, that these patients must daily use

Growth pattern trajectories in boys with Duchenne muscular dystrophy.

OBJECTIVES: The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD). BACKGROUND: We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). RESULTS: The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. CONCLUSION: These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC

Abnormal fatty acid metabolism is a core component of spinal muscular atrophy

Objective: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and subsequent death in young children. Initially considered a motor neuron disease, extra-neuronal involvement is increasingly recognized. The primary goal of this study was to investigate alterations in lipid metabolism in SMA patients and mouse models of the disease. Methods: We analyzed clinical data collected from a large cohort of pediatric SMA type I-III patients as well as SMA type I liver necropsy data. In parallel, we performed histology, lipid analysis, and transcript profiling in mouse models of SMA. Results: We identify an increased susceptibility to developing dyslipidemia in a cohort of 72 SMA patients and liver steatosis in pathological samples. Similarly, fatty acid metabolic abnormalities were present in all SMA mouse models studied. Specifically, Smn2B/- mice displayed elevated hepatic triglycerides and dyslipidemia, resembling non-alcoholic fatty liver disease (NAFLD). Interestingly, this phenotype appeared prior to denervation. Interpretation: This work highlights metabolic abnormalities as an important feature of SMA, suggesting implementation of nutritional and screening guidelines in patients, as such defects are likely to increase metabolic distress and cardiovascular risk. This study emphasizes the need for a systemic therapeutic approach to ensure maximal benefits for all SMA patients throughout their life

Systematic Review on the Potential Effect of Berry Intake in the Cognitive Functions of Healthy People

The increase in life expectancy poses health challenges, such as increasing the impairment of cognitive functions. Berries show a neuroprotective effect thanks to flavonoids, able to reduce neuroinflammatory and to increase neuronal connections. The aim of this systematic review is to explore the impact of berries supplementation on cognitive function in healthy adults and the elderly. Twelve studies were included for a total of 399 participants, aged 18–81 years (mean age: 41.8 ± 4.7 years). Six studies involved young adults (23.9 ± 3.7 years), and four studies involved the elderly (60.6 ± 6.4 years). Most studies investigated effects of a single berry product, but one used a mixture of 4 berries. Non-significant differences were detected across cognition domains and methodologies, but significant and positive effects were found for all cognitive domains (attention and concentration, executive functioning, memory, motor skills and construction, and processing speed), and in most cases they were present in more than one study and detected using different methodologies. Although some limitations should be taken into account to explain these results, the positive findings across studies and methodologies elicit further studies on this topic, to endorse the consumption of berries in healthy populations to prevent cognitive decline

Short-term effects of ketogenic diet on anthropometric parameters, body fat distribution, and inflammatory cytokine production in GLUT1 deficiency syndrome

Objective: The aim of this study was to evaluate the effects of a 12-wk ketogenic diet (KD) on inflammatory status, adipose tissue activity biomarkers, and abdominal visceral (VAT) and subcutaneous fat (SAT) in children affected by glucose transporter 1 deficiency syndrome GLUT1 DS. Methods: We carried out a short-term longitudinal study on 10 children (mean age: 8.4 y, range 3.3–12 y, 5 girls, 5 boys) to determine fasting serum proinflammatory cytokines (high sensitivity C-reactive protein, tumor necrosis factor-a interleukin-6), adipocyte-derived chemokines (leptin and adiponectin), lipid profile, homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity index (QUICKI), anthropometric measurements, and VAT and SAT (by ultrasonography). Results: Children showed no significant changes in inflammatory and adipose tissue activity biomarkers, blood glucose, lipid profile, anthropometric measurements, VAT, and SAT. Fasting insulin decreased (6 3.2 mU/mL versus 3 2 mU/mL; P ¼ 0.001), and both HOMA-IR and QUICKI indexes were significantly modified (1.2 0.6 versus 0.6 0.4; P ¼ 0.002; 0.38 0.03 versus 0.44 0.05; P ¼ 0.002, respectively). Conclusions: Only HOMA-IR and QUICKI indexes changed after 12 wk on a KD, suggesting that over a short period of time KD does not affect inflammatory cytokines production and abdominal fat distribution despite being a high-fat diet. Long-term studies are needed to provide answers concerning adaptive metabolic changes during K

Weight Loss Management and Lifestyle Changes during COVID-19 Lockdown: A Matched Italian Cohort Study

During the COVID-19 lockdown, lifestyle deterioration had a negative impact on weight, and yet no study has focused on patients already undergoing dietary therapy. We performed a cohort study among adults to evaluate the effect of lockdown on weight loss programs, and we investigated changes in eating habits and chronotype. We matched confined cases with non-confined cases among individuals who followed the same diet in 2017–2019. At baseline, all patients underwent a clinical examination and completed questionnaires on lifestyle. At follow-up, patients of the confined group were interviewed by a web call, and questionnaires were re-evaluated. We recruited 61 patients. The confined sample was mainly composed of middle-aged (52 (43,58) years) females (46 (75%)) with overweight (27 (44%)) or obesity (24 (39%)) and a moderate physical activity level (48 (81%)). Body weight at follow-up was significantly higher (1.1 (95% CI: 0.14, 2.1) kg) in the confined group adjusting for all matching variables. Adherence to the Mediterranean diet and eating behavior generally improved. Concerning chronotype, patients differentiated from Neither-types to Evening- and Morning-types. A well-monitored dietary therapy maintains weight loss during lockdown. Improvement in eating habits was observed; however, a shift of the circadian typology occurred

Food and Food Products on the Italian Market for Ketogenic Dietary Treatment of Neurological Diseases

The ketogenic diet (KD) is the first line intervention for glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency, and is recommended for refractory epilepsy. It is a normo-caloric, high-fat, adequate-protein, and low-carbohydrate diet aimed at switching the brain metabolism from glucose dependence to the utilization of ketone bodies. Several variants of KD are currently available. Depending on the variant, KDs require the almost total exclusion, or a limited consumption of carbohydrates. Thus, there is total avoidance, or a limited consumption of cereal-based foods, and a reduction in fruit and vegetable intake. KDs, especially the more restrictive variants, are characterized by low variability, palatability, and tolerability, as well as by side-effects, like gastrointestinal disorders, nephrolithiasis, growth retardation, hyperlipidemia, and mineral and vitamin deficiency. In recent years, in an effort to improve the quality of life of patients on KDs, food companies have started to develop, and commercialize, several food products specific for such patients. This review summarizes the foods themselves, including sweeteners, and food products currently available for the ketogenic dietary treatment of neurological diseases. It describes the nutritional characteristics and gives indications for the use of the different products, taking into account their metabolic and health effects

Long-term follow-up of nutritional status in children with GLUT1 Deficiency Syndrome treated with classic ketogenic diet: a 5-year prospective study

IntroductionThe classic ketogenic diet (cKD) is an isocaloric, high fat, low-carbohydrate diet that induces the production of ketone bodies. High consumption of dietary fatty acids, particularly long-chain saturated fatty acids, could impair nutritional status and increase cardiovascular risk. The purpose of this study was to evaluate the long-term effects of a 5-year cKD on body composition, resting energy expenditure, and biochemical parameters in children affected by Glucose Transporter 1 Deficiency Syndrome (GLUT1DS). MethodsThis was a prospective, multicenter, 5-year longitudinal study of children with GLUT1DS treated with a cKD. The primary outcome was to assess the change in nutritional status compared with pre-intervention, considering anthropometric measurements, body composition, resting energy expenditure, and biochemical parameters such as glucose and lipid profiles, liver enzymes, uric acid, creatinine, and ketonemia. Assessments were conducted at pre-intervention and every 12 months of cKD interventions. ResultsKetone bodies increased significantly in children and adolescents, and remained stable at 5 years, depending on the diet. No significant differences were reported in anthropometric and body composition standards, as well as in resting energy expenditure and biochemical parameters. Bone mineral density increased significantly over time according to increasing age. Body fat percentage significantly and gradually decreased in line with the increase in body weight and the consequent growth in lean mass. As expected, we observed a negative trend in respiratory quotient, while fasting insulin and insulin resistance were found to decrease significantly after cKD initiation. ConclusionLong-term adherence to cKD showed a good safety profile on anthropometric measurements, body composition, resting energy expenditure, and biochemical parameters, and we found no evidence of potential adverse effects on the nutritional status of children and adolescents