Childhood obesity: An overview of laboratory medicine, exercise and microbiome

In the last few years, a significant increase of childhood obesity incidence unequally distributed within countries and population groups has been observed, thus representing an important public health problem associated with several health and social consequences. Obese children have more than a 50% probability of becoming obese adults, and to develop pathologies typical of obese adults, that include type 2-diabetes, dyslipidemia and hypertension. Also environmental factors, such as reduced physical activity and increased sedentary activities, may also result in increased caloric intake and/or decreased caloric expenditure. In the present review, we aimed to identify and describe a specific panel of parameters in order to evaluate and characterize the childhood obesity status useful in setting up a preventive diagnostic approach directed at improving health-related behaviors and identifying predisposing risk factors. An early identification of risk factors for childhood obesity could definitely help in setting up adequate and specific clinical treatments

Exercise, immune system, nutrition, respiratory and cardiovascular diseases during COVID-19: A complex combination

Coronaviruses (CoVs) represent a large family of RNA viruses that can infect different living species, posing a global threat to human health. CoVs can evade the immune response, replicate within the host, and cause a rapid immune compromise culminating in severe acute respiratory syndrome. In humans, the immune system functions are influenced by physical activity, nutrition, and the absence of respiratory or cardiovascular diseases. This review provides an in-depth study between the interactions of the immune system and coronaviruses in the host to defend against CoVs disease

Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo

Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins

Elastic scattering in the 6 , 7 Li + 80 Se systems

Elastic-scattering angular distributions for the 6,7Li+80Se systems were measured at center-of-mass energies from below to above the Coulomb barrier, 13 < Ec.m<24 MeV. The experimental elastic-scattering  cross sections were analyzed within the framework of the optical model to study the energy dependence of the real and imaginary parts of the nuclear-interaction potential. The main objective was to investigate the threshold anomaly, in those weakly bound systems. The behavior of the calculated potentials as a function of energy indicates that our results are qualitatively consistent with the dispersion relation. The threshold anomaly was observed in the 7Li + 80Se and for the 6Li + 80Se system a breakup threshold anomaly is apparent. An analysis of the absorptive processes, involved in the discussion of the experimental results, was performed using th phenomenological optical potentials that best fit the experimental data.Fil: Fimiani, L.. Comisión Nacional de Energía Atómica; ArgentinaFil: Figueira, Juan Manuel. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martí, Guillermo Virginio. Comisión Nacional de Energía Atómica; ArgentinaFil: Testoni, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Pacheco, Alberto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Cárdenas, W. H. Z.. Comisión Nacional de Energía Atómica; ArgentinaFil: Arazi, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Capurro, Oscar Ángel. Comisión Nacional de Energía Atómica; ArgentinaFil: Cardona, Maria Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Carnelli, Patricio Francisco Florencio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: de Barbará, Ezequiel. Comisión Nacional de Energía Atómica; ArgentinaFil: Hojman, Daniel Leonardo. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez Heimann, Diego. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Negri, Agustin Eduardo. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Breakup coupling effects on near-barrier inelastic scattering of the weakly bound 6Li projectile on a 144Sm target

Angular distributions for the inelastic scattering of the weakly bound 6Li nucleus from a 144Sm target (associated with the contributions of both the 2+ and 3- 144Sm excited states together) were measured at bombarding energies close to the Coulomb barrier. The experimental data were compared with expected results based on continuum discretized coupled-channel (CDCC) calculations. The results confirm that it is essential to include continuum?continuum couplings to reproduce the experimental data. The analysis demonstrates that inelastic scattering data can be a critical tool in testing full CDCC calculations involving weakly bound nuclei.Fil: Woodard, A. E.. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Figueira, Juan Manuel. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otomar, D. R.. Universidade Federal Fluminense; BrasilFil: Fernandez Niello, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Lubian, J.. Universidade Federal Fluminense; BrasilFil: Arazi, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Capurro, O. A.. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Carnelli, Patricio Francisco Florencio. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fimiani, L.. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Martí, Guillermo Virginio. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Martinez Heimann, Diego. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monteiro, D. S.. Universidade Federal Fluminense; BrasilFil: Negri, Agustin Eduardo. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Pacheco, Alberto Jorge. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomes, P. R. S.. Universidade Federal Fluminense; Brasi

9^9Be+120^{120}Sn scattering at near-barrier energies within a four body model

Cross sections for elastic and inelastic scattering of the weakly-bound $^9$Be nucleus on a $^{120}$Sn target have been measured at seven bombarding energies around and above the Coulomb barrier. The elastic angular distributions are analyzed with a four-body continuum-discretized coupled-channels (CDCC) calculation, which considers $^9$Be as a three-body projectile ($\alpha$ + $\alpha$ + n). An optical model analysis using the S\~ao Paulo potential is also shown for comparison. The CDCC analysis shows that the coupling to the continuum part of the spectrum is important for the agreement with experimental data even at energies around the Coulomb barrier, suggesting that breakup is an important process at low energies. At the highest incident energies, two inelastic peaks are observed at 1.19(5) and 2.41(5) MeV. Coupled-channels (CC) calculations using a rotational model confirm that the first inelastic peak corresponds to the excitation of the 2$_1^+$ state in $^{120}$Sn, while the second one likely corresponds to the excitation of the 3$_1^-$ state.Comment: 11 pages, 9 figures. Accepted as PR

A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p

RNA activation of haploinsufficient Foxg1 gene in murine neocortex

More than one hundred distinct gene hemizygosities are specifically linked to epilepsy, mental retardation, autism, schizophrenia and neuro-degeneration. Radical repair of these gene deficits via genome engineering is hardly feasible. The same applies to therapeutic stimulation of the spared allele by artificial transactivators. Small activating RNAs (saRNAs) offer an alternative, appealing approach. As a proof-of-principle, here we tested this approach on the Rett syndrome-linked, haploinsufficient, Foxg1 brain patterning gene. We selected a set of artificial small activating RNAs (saRNAs) upregulating it in neocortical precursors and their derivatives. Expression of these effectors achieved a robust biological outcome. saRNA-driven activation (RNAa) was limited to neural cells which normally express Foxg1 and did not hide endogenous gene tuning. saRNAs recognized target chromatin through a ncRNA stemming from it. Gene upregulation required Ago1 and was associated to RNApolII enrichment throughout the Foxg1 locus. Finally, saRNA delivery to murine neonatal brain replicated Foxg1-RNAa in vivo

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting. Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt &lt; 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016). Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH