Medical treatment of weight loss in children and adolescents with obesity.

Obesity remains one of the biggest health problems both in adults and children. Lifestyle modification, including diet and exercise, continues to be the mainstay of obesity prevention and treatment. Unfortunately, lifestyle modifications are often unsuccessful. Pharmacological treatment of obesity in pediatric patients can be applied in selected cases, and not before evidence of failure of the multidisciplinary lifestyle intervention. In this narrative review, we revised the most up-to-date evidence on medical treatment of weight loss in children and adolescents with obesity, including FDA- or EMA-approved and -experimented, not approved, drugs for pediatric population. Multidisciplinary treatment of childhood obesity, regulation of appetite control, energy balance and body weight were also discussed, in order to clarify the indications and mechanism action of drugs. Despite a substantial number of medications used for the treatment of obesity in adults, a limited number of drugs are approved by the drug regulatory agencies for pediatric population. Further research is needed to evaluate the efficacy and safety of novel pharmacological approaches for treatment of pediatric obesity in order to optimize weight management for children and adolescents and limit the development obesity-related comorbidities.

New chiral amino alcohol ligands for catalytic enantioselective addition of diethylzincs to aldehydes.

A study aimed at the synthesis and structure optimization of new, efficient, optically active ß-amino alcohol ligands with a structure suitable for immobilization on magnetite nanoparticles has been carried out. The optimized homogeneous amino alcohol catalysts 13a and 13b, the chirality of which arises from the Sharpless epoxidation of suitable allyl alcohols, were tested by employing the well-established enantioselective amino alcohol-promoted addition of diethylzinc to benzaldehyde, giving the corresponding benzyl alcohol with nearly quantitative yield and ee = 95%. Then, their broad applicability as chiral catalysts was evaluated by carrying out the same reaction on a family of aldehydes, including variously substituted aromatic ones as well as an aliphatic analogue. The results have confirmed the validity of the fine-tuning process performed on ligands 13a and 13b. In fact, both exhibited excellent catalytic activity as demonstrated by the chemical yields and ee obtained from all the tested aldehydes, almost independent of the position and type of substitution in the aromatic ring.

Can obesity exacerbate hyperinsulinaemia in the presence of the mutation of an insulin receptor gene?

Insulin receptor gene (INSR) mutations are a relatively rare and diverse cause of insulin resistance (IR), typically associated with a lean phenotype. However, we present a unique case of severe obesity and Type A severe IR syndrome in a patient with a heterozygous mutation of the INSR gene. Next Generation Sequencing (NGS) analysis was conducted to identify the genetic variant. A 16-year-old girl with severe obesity (BMI-SDS +2.79) exhibited markedly elevated basal insulin levels (>800 mcU/L). Despite obesity being a known cause of hyperinsulinism, further investigation was pursued due to the severity of hyperinsulinaemia. A heterozygous nucleotide variant at the donor splicing site of intron 13 (c.2682 + 1G > A) of the INSR gene was identified. This mutation was also present in the proband's normal-weight mother and her two younger brothers with obesity. Metformin treatment provided limited benefits, but subsequent liraglutide therapy resulted in weight loss and decreased IR 3 months after initiation. Our findings suggest that obesity can exacerbate hyperinsulinaemia in individuals with an INSR gene mutation. Although INSR signalling defects play a minor role in the aetiology of IR, they should still be considered in the diagnostic pathway, particularly in severe phenotypes. Clinicians should not overlook the possibility of genetic causes in patients with obesity and IR, as they may require personalized management approaches.

Links between Childhood Obesity, High-Fat Diet, and Central Precocious Puberty.

In recent years, the existing relationship between excess overweight and central precocious puberty (CPP) has been reported, especially in girls. Different nutritional choices have been associated with different patterns of puberty. In particular, the involvement of altered biochemical and neuroendocrine pathways and a proinflammatory status has been described in connection with a high-fat diet (HFD). In this narrative review, we present an overview on the relationship between obesity and precocious pubertal development, focusing on the role of HFDs as a contributor to activating the hypothalamus-pituitary-gonadal axis. Although evidence is scarce and studies limited, especially in the paediatric field, the harm of HFDs on PP is a relevant problem that cannot be ignored. Increased knowledge about HFD effects will be useful in developing strategies preventing precocious puberty in children with obesity. Promoting HFD-avoiding behavior may be useful in preserving children's physiological development and protecting reproductive health. Controlling HFDs may represent a target for policy action to improve global health.

Epidemiology and molecular analyses of respiratory syncytial virus in the 2021-2022 season in northern Italy.

Background: Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection among infants and young children worldwide, with seasonal peaks in January and February. This study aimed to characterize the RSV samples from a pediatric cohort in the 2021-2022 season in Italy. Methods: In total, 104 samples were collected from pediatric patients attending the "Vittore Buzzi" Children's Hospital in Milan, Italy in the 2021-2022 season. RT-PCR and next-generation sequencing were used to discriminate subgroups and obtain whole genomes. Maximum likelihood and Bayesian phylogenetic methods were used to analyze Italian sequences in the European contest and date Italian clusters. Results: The median age was 78 days, and 76.9% of subjects required hospitalization, with a higher proportion of patients under 3 months of age. An equal proportion of subgroups A (GA2.3.5) and B (GB5.0.5a) was found, with significant differences in length of hospitalization, days of supplemental oxygen treatment, and intravenous hydration duration. Phylogeny highlighted 26 and 37 clusters containing quite the total of Italian sequences for RSV-A and -B, respectively. Clusters presented a tMRCA between December 2011-February 2017 and May 2014-December 2016 for A and B subgroups, respectively. Compared to European sequences, specific mutations were observed in Italian strains. Conclusion: These data confirmed a more severe clinical course of RSV-A, particularly in young children. This study permitted the characterization of recent Italian RSV whole genomes, highlighting the peculiar pattern of mutations that needs to be investigated further and monitored.

Preschool-located influenza vaccination and influenza-like illness surveillance: an Italian pilot experience.

BACKGROUND: We describe the first school-located influenza vaccination campaign with quadrivalent live-attenuated influenza vaccine (LAIV) among pre-school children in Italy, coupled with an innovative school-centred influenza-like illnesses (ILIs) surveillance using a self-sampling non-invasive saliva collection method. METHODS: The pilot study was proposed during the 2021/2022 influenza season to fifteen pre-schools in the Milan municipality. LAIV was offered directly in school to all healthy children without contraindications. ILI differential diagnosis was conducted by real-time RT-PCR for influenza A/B and SARS-CoV-2. RESULTS: Five pre-schools were involved in the pilot project and overall, 135 families (31.2%) participated in the study, adhering to both surveillance and vaccination; 59% of families had an immigrant background. No pupil experienced adverse reactions after vaccination. Nineteen saliva samples were collected from sixteen children (11.8%). Six samples (31.6%) tested positive for SARS-CoV-2; none was positive for influenza A/B. CONCLUSIONS: The participation in the immunisation campaign was good, considering possible absences due to COVID-19 pandemic, and the intranasal administration was well tolerated and helped to overcome parental hesitancy. Saliva sampling represented a useful tool to reduce children's stress and increase parents' compliance. The high participation of families with an immigrant background suggests that school-based interventions can represent an effective strategy to overcome socioeconomic and cultural barriers.

Antibiotic-Induced Neutropenia in Pediatric Patients: New Insights From Pharmacoepidemiological Analyses and a Systematic Review.

Aim: to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide spectrum of treatment options and the occurrence of this relatively uncommon but potentially clinically relevant adverse event. Methods: we carried out a pharmacoepidemiological analysis based on the FDA Adverse Event Reporting System (FAERS) database, a retrospective chart review and a systematic review of the literature, focusing on the time to onset (TTO) of this side effect, in the pediatric clinical setting. Results: A total of 281 antibiotic-related neutropenia events, involving 11 categories of antibiotics, were included in the time to onset analysis. The median TTO ranged from 4 to 60 days after the start of the therapy. A shorter median TTO was found from the retrospective chart review [16 patients: median days (25th-75th percentiles) = 4 (3-5)], compared to 15 (9-18) vs. 10 (6-18) for literature (224 patients) and FAERS (41 cases), respectively. The Anatomical Therapeutic Chemical classes, J01X, J01F, J01E and J04A, and the median TTOs retrieved from more than one source revealed high accordance (p > 0.05), with J01X causing neutropenia in less than a week and J01F/J01E/J04A in more than 10 days. Antibiotics were discontinued in nearly 34% of cases. In FDA Adverse Event Reporting System reports, half of the patients experiencing neutropenia were hospitalized. Conclusion: Whereas antibiotic associated neutropenia is benign in the majority of cases, yet it should not be neglected as, even if rarely, it may put children at higher risk of clinical consequences. Clinicians' awareness of antibiotic-associated neutropenia and its mode of presentation contributes to the continuous process of monitoring safety of antibiotics.

HPV Vaccination in Young Males: A Glimpse of Coverage, Parental Attitude and Need of Additional Information from Lombardy Region, Italy.

Background: In the Lombardy Region, Italy, HPV vaccination is recommended and offered free of charge to 12-years-old males since 2017. The expected vaccination thresholds are still far to be reached. Methods: A cross-sectional survey to investigate parents' attitudes towards the HPV vaccine and knowledge about HPV was administered to parents of boys aged 6 to 18 years attending a large pediatric hospital for outpatient specialistic evaluations. Two parallel multiple logistic regression analyses were conducted to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for attitude towards HPV vaccination and perceived need for more information about HPV vaccination. Results: A positive attitude towards HPV vaccination was found in 74% of interviewed parents. Knowledge of HPV, having a generally positive attitude toward vaccination, and mothers filling in the survey were positively associated with a positive attitude to the HPV vaccine. Parents' perceived need for more information about HPV vaccination was positively associated with the child's age, general positive attitude toward vaccination, Christian religion, and positive attitude toward HPV vaccination; knowing that HPV vaccination is free of charge significantly reduced the risk of asking for more information on HPV vaccination. Conclusions: The majority of parents of male children and adolescents in our study have a positive attitude toward HPV vaccination. Attitude toward HPV vaccination and perceived need for more information on HPV vaccination were directly related to a positive attitude toward vaccines in general. In addition, knowledge of HPV and related pathologies favors a positive attitude toward HPV vaccination. Future health programs should target an even wider diffusion of evidence-based information on vaccines in general and on the HPV vaccine in young males, to support a positive attitude toward vaccines in the general population.

Late-Onset Pyloric Stenosis and Intussusception With Final Diagnosis of Food Proteins' Hypersensitivity in Schaaf-Yang Syndrome: A Case Report.

Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder whose clinical spectrum includes neurodevelopment delay, dysmorphic features, and gastrointestinal symptoms such as feeding difficulties, gastroesophageal reflux, and chronic constipation. Given the small number of patients diagnosed with this syndrome, our aim is to describe novel clinical features that have not yet been reported. The patient we are describing is a 14-year-old male affected by a severe form of SYS. Initial clinical presentation included respiratory distress at birth, feeding difficulties, and neurodevelopmental delay. Since the age of 8 months, he had been tube fed with a semi-elemental formula, and this was well tolerated. At 9 years of age, the pathological mutation (variant p.Val701fs in MAGEL2 gene) associated with SYS was diagnosed. At 13 years of age, he presented severe gastrointestinal symptoms associated to progressive feeding difficulties. He also suffered from recurrent pancreatitis, late-onset pyloric stenosis and intussusception. Histology showed duodenal villous atrophy with a negative serology for celiac disease. Food protein's hypersensitivity was diagnosed and symptoms resolved after starting an elemental formula.

Thyroid Function and Metabolic Syndrome in Children and Adolescents with Neuromotor Disability.

Thyroid function plays a crucial role in nervous system integrity and metabolic homeostasis. We evaluated the pattern of TSH, FT4 and FT3 release in children with neuromotor impairment (NI) in relationship with metabolic syndrome (MS). We enrolled 55 patients with NI and 30 controls. Clinical parameters, thyroid function and MS presence were recorded. Principal component analysis (PCA), cluster analysis, and logistic regression models were performed. MS was detected in 54.5% of patients. Four clusters were identified: the first one included only controls and, contrasting with cluster 4, was exclusively characterized by children with disability and MS. This latter showed increased FT4 and FT3 and decreased TSH levels. Cluster 2, characterized by disability without MS showed high FT4 and FT3, whereas cluster 3 with low FT4 and FT3 mainly included disability (90%) and showed prevalent MS (57%). The association between TSH and NI is represented by a U-shape structure. The TSH, FT3 and FT4 release patterns may reflect thyrotropic adaptation, allostatic response and compensatory mechanisms. These mechanisms, found in both MS and disability, show that the odds of having a condition of NI with or without MS increase as the TSH values deviate, in both directions, from a value of 2.5 mLU/mL.

The Diabetic Lung: Insights into Pulmonary Changes in Children and Adolescents with Type 1 Diabetes.

Historically, the lung was not listed and recognized as a major target organ of diabetic injury. The first evidence of diabetic lung involvement was published fifty years ago, with a study conducted in a population of young adults affected by type 1 diabetes (T1D). In recent years, there has been mounting evidence showing that the lung is a target organ of diabetic injury since the beginning of the disease-at the pediatric age. The deeply branched vascularization of the lungs and the abundance of connective tissue, indeed, make them vulnerable to the effects of hyperglycemia, in a way similar to other organs affected by microvascular complications. In this review, we focus on pulmonary function impairment in children and adolescents affected by T1D. We also cover controversial aspects regarding available studies and future perspectives in this field.

Term Infant Formulas Influencing Gut Microbiota: An Overview.

Intestinal colonization of the neonate is highly dependent on the term of pregnancy, the mode of delivery, the type of feeding [breast feeding or formula feeding]. Postnatal immune maturation is dependent on the intestinal microbiome implementation and composition and type of feeding is a key issue in the human gut development, the diversity of microbiome, and the intestinal function. It is well established that exclusive breastfeeding for 6 months or more has several benefits with respect to formula feeding. The composition of the new generation of infant formulas aims in mimicking HM by reproducing its beneficial effects on intestinal microbiome and on the gut associated immune system (GAIS). Several approaches have been developed currently for designing new infant formulas by the addition of bioactive ingredients such as human milk oligosaccharides (HMOs), probiotics, prebiotics [fructo-oligosaccharides (FOSs) and galacto-oligosaccharides (GOSs)], or by obtaining the so-called post-biotics also known as milk fermentation products. The aim of this article is to guide the practitioner in the understanding of these different types of Microbiota Influencing Formulas by listing and summarizing the main concepts and characteristics of these different models of enriched IFs with bioactive ingredients.

High yield synthesis of pure alkanethiolate-capped silver nanoparticles.

One-phase, one-pot synthesis of Ag(0) nanoparticles capped with alkanethiolate molecules has been optimized to easily achieve a pure product in quantitative yield. We report the synthesis of dodecanethiolate-capped silver particles and the chemophysical, structural, and morphologic characterization performed by way of UV-vis, (1)H NMR, and X-ray photoelectron (XPS) spectroscopies, X-ray powder diffraction (XRD) and X-ray absorption fine structure analysis (XFAS), electron diffraction and high-resolution transmission electron microscopy (HR-TEM), and scanning and transmission electron microscopy (SEM and TEM). Depending on the molar ratio of the reagents (dodecylthiosulphate/Ag(+)), the mean Ag(0) particle size D(XRD) is tuned from 4 to 3 nm with a narrow size distribution. The particles are highly soluble, very stable in organic solvents (hexane, toluene, dichloromethane, etc.), and resistant to oxidation; the hexane solution after one year at room temperature does not show any precipitation or formation of oxidation byproducts.

NHC-catalysed aerobic aldehyde-esterifications with alcohols: no additives or cocatalysts required.

A highly efficient, broad scope, additive-free mild protocol for the oxidative carbene-catalysed esterification of aldehydes (including the related aqueous oxidation to acids) has been developed.

Control of silver-polymer aggregation mechanism by primary particle spatial correlations in dynamic fractal-like geometry.

Silver nanocrystals have been prepared by reacting silver nitrate with ascorbic acid in aqueous solution containing a low concentration of a commercial polynaphthalene sulfonate polymer (Daxad 19). Various crystalline morphologies have been obtained simply by tuning the reaction temperature. We have investigated the nanoparticle formation mechanism at three different temperatures by in situ and time resolved small angle X-ray scattering measurements. By modeling the scattering intensity with interacting spherical particles in a fractal-like polymer-Ag matrix, we found signatures of nucleation, growth and assembly of primary particles of about 15-20 nm. We observed how the time evolution of both spatial correlations between primary particles and the dynamic fractal geometry of the polymer-Ag matrix could influence and determine both the aggregation mechanism and the morphology of forming nanostructures in solution.

Monitoring early stages of silver particle formation in a polymer solution by in situ and time resolved small angle X-ray scattering.

Silver particles have been prepared by reduction of silver nitrate with ascorbic acid in acidic aqueous solution containing a low concentration of a commercial polynaphthalene sulfonate polymer (Daxad 19) as dispersant agent. The reduction has been induced and controlled by the slow addition of ascorbic acid at a fixed rate; in this way, we were able to monitor the formation of a silver crystalline colloidal dispersion by in situ and time resolved Small Angle X-ray Scattering measurements. Modeling the scattering intensity with interacting spherical particles in a polymer-Ag like-fractal template allowed us to distinguish different stages involving liquid-like ordered cluster nucleation, cluster growth up to primary particle formation and particle coalescence. Between primary particle formation and particle coalescence, we observed the occurrence of a transient phase of core-shell type structures having primary particles as stable cores in expanding shells built by the organic polymer. We discuss these results in a twofold perspective pertaining both to technology, relative to controlled fabrication of metal nanoparticles and to basic chemical physics, dealing with non standard stepwise crystallization from solutions.

Which role for pre-treatment laparoscopic staging?

OBJECTIVE: To investigate in cervical cancer patients the impact of pre-treatment laparoscopic staging on treatment plan and disease free survival. METHODS: A review of the present literature has been performed and data have been compared to results obtained in a large series of patients not surgically staged. RESULTS: Among 134 abstracts resulting from Medline research, 13 were deemed potentially relevant to the study questions. The presence of intraperitoneal diffusion of disease can be recognized in locally advanced cervical cancer patients (LACC) in a percentage ranging between 1.9% and 29%. The rate of aortic positive nodes in clinically negative LACC patients cases has been reported between 11% and 25%, by laparoscopy. In our Division, 152 LACC patients have been treated between October 1997 and February 2007. None of the patients has been submitted to pre-treatment laparoscopic staging, whereas in all cases a pre-operative MRI has been performed. With a median follow-up 28.0 months (range 3-126 months), 31 recurrences have been observed. The 5-year DFS has been 83% and OS 90%. Although only a retrospective analysis can be carried out, such result well compares to cases surgically staged. CONCLUSIONS: Pre-treatment surgical staging can identify positive nodes in LACC patients considered clinically negative, and recognize intraperitoneal disease, thus making the physician tailor the treatment on the bases of histopathological result. Moreover, it offers the potential advantage of debulking of macroscopically positive nodes, and to transpose the ovary outside the radiation. However, the positive impact on DFS has still to be demonstrated.