Bioactive compounds in childhood obesity and associated metabolic complications: Current evidence, controversies and perspectives

Obesity represents the most frequent chronic disease among children worldwide, with a significant global burden on society. Metabolically unhealthy obesity (MUO) can affect children since their first years of life, and novel therapeutic strategies to tackle metabolic complications are under investigation. This review focuses on bioactive compounds and their possible beneficial effects on obesity, particularly omega-3, docosahexaenoic acid, vitamin D, biotics, polysaccharide macromolecules, polyphenols, inositols, alpha lipoic acid, and bromelaine. Our aim is to summarize current evidence about bioactive compounds in the treatment of obesity, highlighting recent findings on their use in children and adolescents. Most studied molecules are omega-3 and vitamin D, despite the heterogeneity between the studies. Moreover, given the emerging interest in the gut-brain axis in the link between metabolic health and microbiota, various studies on prebiotics, probiotics, synbiotics, postbiotics and polysaccharide macromolecules have been considered. Some preclinical studies seem to highlight a possible role of the polyphenols, even if their clinical evidence is still discussed. Lastly, we describe possible effects of inositols and alpha-lipoic acid. Despite some dietary supplements seem to be promising in overweight subjects, only in a few of them a dose/response efficacy has been found in the pediatric age. Innovative, well-designed and targeted clinical trials are then needed to prove the beneficial effects of these compounds that could support the standard behavioral therapy for obesity

Photon-number resolving detector based on a series array of superconducting nanowires

We present the experimental demonstration of a superconducting photon number resolving detector. It is based on the series connection of N superconducting nanowires, each connected in parallel to an integrated resistor. The device provides a single voltage readout, proportional to the number of photons absorbed in distinct nanowires. Clearly separated output levels corresponding to the detection of n=1-4 photons are observed in a 4-element detector fabricated from an NbN film on GaAs substrate, with a single-photon system quantum efficiency of 2.6% at the wavelength of 1300nm. The series-nanowire structure is promising in view of its scalability to large photon numbers and high efficiencies.Comment: 12 pages, 6 figure

Ultrasensitive N-photon interferometric autocorrelator

We demonstrate a novel method to measure the Nth-order (N=1, 2, 3, 4) interferometric autocorrelation with high sensitivity and temporal resolution. It is based on the combination of linear absorption and nonlinear detection in a superconducting nanodetector, providing much higher efficiency than methods based on all-optical nonlinearities. Its temporal resolution is only limited by the quasi-particle energy relaxation time, which is directly measured to be in the 20 ps range for the NbN films used in this work. We present a general model of interferometric autocorrelation with these nonlinear detectors and discuss the comparison with other approaches and possible improvements

Effects of polluted air-masses advection on atmospheric particles in a semi-rural site in south Italy by SEM-EDX analysis

The variation of aerosol properties under polluted air masses advection was studied in a semi-rural site in South Italy, by means of SEM-EDX analysis performed on particles collected on 13-stages impactor filters. Radiometric measurements, HYSPLIT back-trajectories and NAAPS maps helped to choose four measurement days of polluted air mass circulation, two of them collected in the warm season (31 July 2008, 16 September 2010) and two in the cold one (16 April 2009, 18 March 2010). Polluted aerosol characteristics were compared to those under background (BG) conditions (8 February 2011), highlighting differences in the particles chemical and morphological properties. One of the signatures of the air mass transport in the coarse fraction was the higher content of particles containing S, i.e., S-reacted, (27.5% on average) in comparison with BG conditions (1%). Two main sources of transported aerosols were identified: industrial processes and biomass burning, with fly ash, metal and S-rich particles in the first case, and K-salts and nitrate-coated Ca-bearingparticles in the second. Single particle analysis on the coarse fraction allowed large agglomerates of soot to be identified, with inclusions of silicate particles rich in Cu and Zn, Ca-S, fly ash and metals particles that are a clear indication of extensive modifications of aerosol size, chemical composition and, likely, radiative properties. In finer stages (EAD ≤ 0.94 μm) concurrent collection of organic and inorganic particles originated an agglomerate state matter mainly characterized by K and S for polluted conditions and by K only for BG

Peri-Implant Bone Loss and Overload: A Systematic Review Focusing on Occlusal Analysis through Digital and Analogic Methods.

The present review aimed to assess the possible relationship between occlusal overload and peri-implant bone loss. In accordance with the PRISMA guidelines, the MEDLINE, Scopus, and Cochrane databases were searched from January 1985 up to and including December 2021. The search strategy applied was: (dental OR oral) AND implants AND (overload OR excessive load OR occlusal wear) AND (bone loss OR peri-implantitis OR failure). Clinical studies that reported quantitative analysis of occlusal loads through digital contacts and/or occlusal wear were included. The studies were screened for eligibility by two independent reviewers. The quality of the included studies was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. In total, 492 studies were identified in the search during the initial screening. Of those, 84 were subjected to full-text evaluation, and 7 fulfilled the inclusion criteria (4 cohort studies, 2 cross-sectional, and 1 case-control). Only one study used a digital device to assess excessive occlusal forces. Four out of seven studies reported a positive correlation between the overload and the crestal bone loss. All of the included studies had moderate to serious overall risk of bias, according to the ROBINS-I tool. In conclusion, the reported data relating the occlusal analysis to the peri-implant bone level seem to reveal an association, which must be further investigated using new digital tools that can help to standardize the methodology

Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis

Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until February 12th, 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80-100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [n = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65-1.41]

Empathy and perceived burden in caregivers of patients with schizophrenia spectrum disorders

Background Caregivers of patients load different kinds of burdens, including emotional distress. Aims of this study were to evaluate both burden and empathy of caregivers who assist patients with schizophrenia spectrum disorders. Methods We selected a sample of 60 caregivers (34 women and 26 men), who assisted patients with schizophrenia spectrum disorders treated in our local Community Mental Health Center for a 1-year minimum period. We administered two scales to our sample, Zarit Burden Interview (ZBI) and Balanced Emotional Empathy Scale (BEES), and collected data of caregivers and their assisted patients in a 3-month period. Data were statistically analyzed. Results We reported a mean ZBI score of 49.68 (±15.03 SD) and a mean BEES score of 14.35 (±9.05 SD), indicating the perception of moderate-severe burden and low level of empathy, respectively. The analysis of internal consistency confirmed the good reliability of both ZBI (Cronbach’s alpha = 0.90) and BEES (Cronbach’s alpha = 0.77). The correlation between the two scales was not statistically significant at Spearman test. At our multiple linear regression, many variables of both caregiver and patient showed a significant correlation with the ZBI score. In particular, not living with the assisted patient and female gender of caregiver potentially decreased the burden, whereas clinical severity of assisted patient and two caregiver conditions, middle school education and spouse relationship with patient, could worsen the burden. We highlighted two positive statistically significant correlations between the total score of BEES and caregiver characteristics: being spouse and not living with assisted patient. Conclusions Our study highlights that the caregiver burden of patients with severe psychiatric disorders is high and is associated with low emotional empathy experienced by caregivers, probably due to a defensive psychological mechanism. The conditions of spouse and cohabitation can concomitantly increase both empathy and burden in caregivers

Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production

Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases