Metabolic control of DNA methylation in naive pluripotent cells.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions

Metabolic control of DNA methylation in naive pluripotent cells.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions

Gli avvelenamenti nel settorato medico-legale pisano nel decennio 1999 – 2008

Gli autori riportano i dati statistici relativi agli avvelenamenti verificatisi nel settorato medico-legale pisano nel decennio 1999-2008 in rapporto alle richieste totali di esami tossicologici, comprese quelle non correlate alle cause della morte, alla natura delle sostanze implicate nella morte per intossicazione, alle modalità lesive, alle fasce di età. Dal confronto dei risultati ottenuti dall’elaborazione di tali dati con quelli relativi a loro precedenti lavori di casistica, detti autori mettono in luce principalmente come sia confermata l’escalation delle morti da droga, passate dal 28% del totale dei decessi ricon

A family-based education program for obesity: a three-year study

Abstract Background The epidemic of obesity is increasing in all countries. However, the number of controlled studies focusing on childhood obesity, with a long follow-up is still limited. Even though Behavioral Therapy shows some efficacy, it requires a prolonged teamwork that is not always available in public health settings. In addition, Behavioral Therapy is not always accepted. We describe a new intensive and sustainable family-based, Therapeutic Education program for childhood obesity. Methods Controlled clinical study: a family-based Therapeutic Education program without dietetic prescription involving overweight and obese children/adolescents, without evident psychological troubles, and their families. The program consisted of three clinical and therapeutic education sessions, carried out by a single physician. Further sessions were carried out every six months in the first year and then every year. Study population: 190 overweight children, 85 treated with a therapeutic education program (45 males and 40 females, mean age of 10.43 ± 3) with an average BMI% of 154.72 ± 19.6% and 105 matched children, treated with traditional dietary approach. Children's Body Mass Index (BMI) % and BMI Standard Deviation Score measured at baseline and after a three year-follow-up, were compared. Statistical tests: ANOVA-RM (repeated measures) controlled for distribution by Kolmogorov-Smirnov, Bartlett's test or correspondent non-parametric procedures, X2 tests or Fisher's exact test and simple linear regression. Results After a follow-up of 2.7 ± 1.1 years, 72.9% of the children who followed the Therapeutic Education Program obtained a BMI% reduction, compared to 42.8% of children who followed the traditional dietary treatment. Weight reduction was good in moderately obese children and in the severely obese. In addition, a smaller proportion of children treated with therapeutic education had negative results (BMI increase of >10%) compared to those treated with dietary approach (11.8% vs. 25.7%); finally, periodic phone calls reduced the drop-out rate in the therapeutic education group. Conclusion These results indicate the efficacy and sustainability of the Therapeutic Education program, that was completely carried out by a single pediatrician; in addition, it met with an elevated participant acceptance, suggesting a convenient therapeutic solution for skilled pediatricians and selected obese children, when Behavioral Therapy is not available or teamwork is poor.</p

Nonlinear seismic soil-foundation interaction: analysis and modelling methods

Dottorato di ricerca in ingegneria sismica. 11. ciclo. Relatore E. Faccioli. Correlatore R. NovaConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Évaluation clinique d’un programme d’éducation thérapeutique centré sur les familles d’enfants et d’adolescents obèses ou en surpoids

Dans la lutte contre l’obésité infantile, si la thérapie comportementale montre certains résultats, celle-ci est difficile à proposer à tous les enfants. Objectif : Pour concerner un plus grand nombre d’enfants et leur famille, nous proposons un programme d’éducation thérapeutique dit intensif et son évaluation clinique. Méthode : Il s’agit d’une étude rétrospective. Après une évaluation clinique de l’enfant et de la compréhension familiale de sa situation de santé, le programme se poursuit par une séance d’éducation collective ainsi qu’une session d’évaluation à distance. Puis, chaque année, des consultations cliniques et éducatives sont proposées. Population : L’étude concerne 254 enfants en surpoids ou obèses. Au total, 127 jeunes enfants d’âge moyen 10,45  ± 3 avec un IMC% 158,35  ± 18,6 % ont été inclus dans le programme d’éducation thérapeutique. Le groupe contrôle comprenait 127 jeunes enfants. Ils ont suivi un programme traditionnel comprenant des explications et des conseils sur l’activité physique et la diététique. Résultats : Après un suivi de 2,8  ± 1,3 ans, l’IMC % du groupe de l’étude a diminué de 10,2  ± 16,6 %; avec une réduction du nombre d’enfants avec une obésité sévère de 50 %. Le programme d’éducation thérapeutique a rencontré une satisfaction élevée auprès des familles. Conclusion : Les résultats montrent une certaine efficacité de ce programme d’éducation thérapeutique qui pourrait représenter une alternative à d’autres approches thérapeutiques d’une durée plus longue. Sa valeur clef est sa faisabilité et son accessibilité