The chiral 1:2 adduct (S)S(S)C(-)589-ethyl 2-phenylbutyl sulphide-mercury (II) chloride:(-)589[(S)S(S)C-Et(2-PhBu)S.(HgCl2)2]. Stereoselective synthesis, asymmetric oxidation, crystal and molecular structure and circular dichroism spectra

Optically active (-)589ethyl (S)-2-phenylbutyl thioether, (-)(S)C-Et(PhBu)S (I), and its new diastereoisomeric mercury (II) chloride adduct, 1:2, (-)[(S)S(S)C-Et(PhBu)S.(HgCl2)2]2, (II) were stereoselectively synthesized; the absorbance (UV) and circular dichroism (CD) spectra were measured and the crystal and molecular structure of complex (II) was determined by single-crystal X-ray diffraction. Two different Hg centres are present whose coordination environments are built by two short bonds to chloride ligands in one case, and to one chloride and one sulphur in the other one. These originate digonal units. Electroneutrality is achieved by a further chlorine, which can be considered prevalently ionic and bonded to the two Hg centres, forming square bridging systems nearly perpendicular to the digonal molecules. The coordination polyhedra can be interpreted as 2 + 4 tetragonally-compressed octahedra with the four longer contacts lying in the equatorial plane. IR spectroscopic data are consistent with the presence of one bent and one linear Cl–Hg–Cl moiety. The absolute configurations at both stereogenic centres of the formed diastereoisomeric complex (II) are (S). The (S)S absolute configuration at the stereogenic sulphur atom bonded to the mercury(II) atom in complex (II) has been related with the negative Cotton effect assigned in its circular dichroism (CD) spectrum to a charge-transfer transition at ca. 230 nm. The stereoselective oxidation of (I) and (II) with hydrogen peroxide, induced by the stereogenic carbon atom (S)C of the enantiopure sulphide, gave (-)598ethyl (S)C-2-phenylbutyl(S)S-sulphoxide, (-)598[(S)S(S)C-Et(PhBu)SO], (III), having 18.1% de. Oxidations carried out in the presence of a 200 molar excess of mercury(II) chloride gave (-)598ethyl (S)C-2-phenylbutyl(R)S-sulphoxide, (-) 598[(R)S(S)C-Et(PhBu)SO], (IV) with 31% de, showing the cooperative influence of mercury(II) chloride on the selectivity of the oxidation reaction

Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation

Cleft lip and palate (CL/P) is the most prevalent craniofacial birth defect in humans. None of the surgical procedures currently used for CL/P repair lead to definitive correction of hard palate bone interruption. Advances in tissue engineering and regenerative medicine aim to develop new strategies to restore palatal bone interruption by using tissue or organ-decellularized bioscaffolds seeded with host cells. Aim of this study was to set up a new natural scaffold deriving from a decellularized porcine mucoperiosteum, engineered by an innovative micro-perforation procedure based on Quantum Molecular Resonance (QMR) and then subjected to in vitro recellularization with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Our results demonstrated the efficiency of decellularization treatment gaining a natural, non-immunogenic scaffold with preserved collagen microenvironment that displays a favorable support to hMSC engraftment, spreading and differentiation. Ultrastructural analysis showed that the micro-perforation procedure preserved the collagen mesh, increasing the osteoinductive potential for mesenchymal precursor cells. In conclusion, we developed a novel tissue engineering protocol to obtain a non-immunogenic mucoperiosteal scaffold suitable for allogenic transplantation and CL/P repair. The innovative micro-perforation procedure improving hMSC osteogenic differentiation potentially impacts for enhanced palatal bone regeneration leading to future clinical applications in humans

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults

Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations. CONCLUSIONS: The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient

Towards a framework for critical citizenship education

Increasingly countries around the world are promoting forms of "critical" citizenship in the planned curricula of schools. However, the intended meaning behind this term varies markedly and can range from a set of creative and technical skills under the label "critical thinking" to a desire to encourage engagement, action and political emancipation, often labelled "critical pedagogy". This paper distinguishes these manifestations of the "critical" and, based on an analysis of the prevailing models of critical pedagogy and citizenship education, develops a conceptual framework for analysing and comparing the nature of critical citizenship

The sub-seasonal to seasonal prediction (S2S) project database

A database containing sub-seasonal to seasonal forecasts from 11 operational centres is available to the research community and will help advance our understanding of the sub-seasonal to seasonal time range. Demands are growing rapidly in the operational prediction and applications communities for forecasts that fill the gap between medium-range weather and long-range or seasonal forecasts. Based on the potential for improved forecast skill at the sub-seasonal to seasonal time range, a sub-seasonal prediction (S2S) research project has been established by the World Weather Research Program/World Climate Research Program. A main deliverable of this project is the establishment of an extensive database, containing sub-seasonal (up to 60 days) forecasts, 3-weeks behind real-time, and reforecasts from 11 operational centers, modelled in part on the THORPEX Interactive Grand Global Ensemble (TIGGE) database for medium range forecasts (up to 15 days). The S2S database, available to the research community since May 2015, represents an important tool to advance our understanding of the sub-seasonal to seasonal time range that has been considered for a long time as a “desert of predictability”. In particular, this database will help identify common successes and shortcomings in the model simulation and prediction of sources of sub-seasonal to seasonal predictability. For instance, a preliminary study suggests that the S2S models underestimate significantly the amplitude of the Madden Julian Oscillation (MJO) teleconnections over the Euro-Atlantic sector. The S2S database represents also an important tool for case studies of extreme events. For instance, a multi-model combination of S2S models displays higher probability of a landfall over Vanuatu islands 2 to 3 weeks before tropical cyclone Pam devastated the islands in March 2015

Adolescents with metabolic syndrome have a history of low aerobic fitness and physical activity levels

Abstract: Purpose: Metabolic syndrome (MS) is a clustering of cardiovascular disease risk factors that identifies individuals with the highest risk for heart disease. Two factors that may influence the MS are physical activity and aerobic fitness. This study determined if adolescent with the MS had low levels of aerobic fitness and physical activity as children. Methods: This longitudinal, exploratory study had 389 participants: 51% girls, 84% Caucasian, 12% African American, 1% Hispanic, and 3% other races, from the State of North Carolina. Habitual physical activity (PA survey), aerobic fitness (VO2max), body mass index (BMI), blood pressure, and lipids obtained at 7–10 y of age were compared to their results obtained 7 y later at ages 14–17 y. Results: Eighteen adolescents (4.6%) developed 3 or more characteristics of the MS. Logistic regression, adjusting for BMI percentile, blood pressure, and cholesterol levels, found that adolescents with the MS were 6.08 (95%CI = 1.18–60.08) times more likely to have low aerobic fitness as children and 5.16 (95%CI = 1.06–49.66) times more likely to have low PA levels. Conclusion: Low levels of childhood physical activity and aerobic fitness are associated with the presence of the metabolic syndrome in adolescents. Thus, efforts need to begin early in childhood to increase exercise

Efficacy of a meal replacement diet plan compared to a food-based diet plan after a period of weight loss and weight maintenance: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Obesity has reached epidemic proportions in the United States. It is implicated in the development of a variety of chronic disease states and is associated with increased levels of inflammation and oxidative stress. The objective of this study is to examine the effect of Medifast's meal replacement program (MD) on body weight, body composition, and biomarkers of inflammation and oxidative stress among obese individuals following a period of weight loss and weight maintenance compared to a an isocaloric, food-based diet (FB).</p> <p>Methods</p> <p>This 40-week randomized, controlled clinical trial included 90 obese adults with a body mass index (BMI) between 30 and 50 kg/m², randomly assigned to one of two weight loss programs for 16 weeks and then followed for a 24-week period of weight maintenance. The dietary interventions consisted of Medifast's meal replacement program for weight loss and weight maintenance, or a self-selected, isocaloric, food-based meal plan.</p> <p>Results</p> <p>Weight loss at 16 weeks was significantly better in the Medifast group (MD) versus the food-based group (FB) (12.3% vs. 6.9%), and while significantly more weight was regained during weight maintenance on MD versus FB, overall greater weight loss was achieved on MD versus FB. Significantly more of the MD participants lost ≥ 5% of their initial weight at week 16 (93% vs. 55%) and week 40 (62% vs. 30%). There was no difference in satiety observed between the two groups during the weight loss phase. Significant improvements in body composition were also observed in MD participants compared to FB at week 16 and week 40. At week 40, both groups experienced improvements in biochemical outcomes and other clinical indicators.</p> <p>Conclusions</p> <p>Our data suggest that the meal replacement diet plan evaluated was an effective strategy for producing robust initial weight loss and for achieving improvements in a number of health-related parameters during weight maintenance, including inflammation and oxidative stress, two key factors more recently shown to underlie our most common chronic diseases.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT01011491</p

Fault diagnosis for uncertain networked systems

Fault diagnosis has been at the forefront of technological developments for several decades. Recent advances in many engineering fields have led to the networked interconnection of various systems. The increased complexity of modern systems leads to a larger number of sources of uncertainty which must be taken into consideration and addressed properly in the design of monitoring and fault diagnosis architectures. This chapter reviews a model-based distributed fault diagnosis approach for uncertain nonlinear large-scale networked systems to specifically address: (a) the presence of measurement noise by devising a filtering scheme for dampening the effect of noise; (b) the modeling of uncertainty by developing an adaptive learning scheme; (c) the uncertainty issues emerging when considering networked systems such as the presence of delays and packet dropouts in the communication networks. The proposed architecture considers in an integrated way the various components of complex distributed systems such as the physical environment, the sensor level, the fault diagnosers, and the communication networks. Finally, some actions taken after the detection of a fault, such as the identification of the fault location and its magnitude or the learning of the fault function, are illustrated

Dietary inflammatory index and inflammatory biomarkers in adolescents from LabMed physical activity study

Background/objectives The dietary inflammatory index (DII) is a tool to measure the diet’s inflammatory potential and has been used with adults to predict low-grade inflammation. The present study aims to assess whether this dietary score predicts low-grade inflammation in adolescents. Subjects/methods The sample comprises 329 adolescents (55.9% girls), aged 12–18 years, from LabMed Physical Activity Study. DII score was calculated based on a food-frequency questionnaire and categorized into tertiles. We collected blood samples to determine the follow inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), complement component 3 (C3), and 4 (C4). In addition we calculated an overall inflammatory biomarker score. Odds ratios (OR) and 95% confidence intervals (95%CI) were computed from binary logistic regression models. Results DII score, comparing first with third tertile, was positively associated with IL-6 in crude model (OR = 1.88, 95% CI:1.09–3.24, ptrend = 0.011) and in fully adjusted (for biological and lifestyle variables) (OR = 3.38, 95%CI:1.24–9.20, ptrend = 0.023). Also, DII score was positively associated with C4, when fully adjusted (OR = 3.12, 95%CI:1.21–8.10, ptrend = 0.016). DII score was negatively associated with C3 in crude model, comparing first with second but not with third tertile, and no significant associations in fully adjusted model were observed, although a trend was found (OR = 1.71, 95% CI:0.63–4.66, ptrend = 0.044). No significant associations were observed between DII score and CRP. However, DII score was positively associated with the overall inflammatory biomarker score, when fully adjusted (OR = 5.61, 95% CI:2.00–15.78, ptrend = 0.002). Conclusions DII score can be useful to assess the diet’s inflammatory potential and its association with low-grade inflammation in adolescents.The authors gratefully acknowledged the participation of all adolescents and their parents, teachers and schools of the LabMed and Physical Activity Study, the cooperation of volunteer’s, the Department of Hygiene and Epidemiology (University of Porto) for the conversion food frequency questionnaire data into nutrients, and the Research Centre in Physical Activity, Health and Leisure (University of Porto) for the sponsoring the LabMed and Physical Activity Study.info:eu-repo/semantics/publishedVersio