A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype

Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder characterized by unexplained left ventricle hypertrophy associated with non-dilated ventricular chambers. Several genes encoding heart sarcomeric proteins have been associated to HCM, but a small proportion of HCM patients harbor alterations in other non-sarcomeric loci. The variable expression of HCM seems influenced by genetic modifier factors and new sequencing technologies are redefining the understanding of genotype–phenotype relationships, even if the interpretations of the numerous identified variants pose several challenges. Methods and results: We investigated 62 sarcomeric and non-sarcomeric genes in 41 HCM cases and in 3 HCM-related disorders patients. We employed an integrated approach that combines multiple tools for the prediction, annotation and visualization of functional variants. Genotype–phenotype correlations were carried out for inspecting the involvement of each gene in age onset and clinical variability of HCM. The 80% of the non-syndromic patients showed at least one rare non-synonymous variant (nsSNV) and among them, 58% carried alterations in sarcomeric loci, 14% in desmosomal and 7% in other non-sarcomeric ones without any sarcomere change. Statistical analyses revealed an inverse correlation between the number of nsSNVs and age at onset, and a relationship between the clinical variability and number and type of variants. Conclusions: Our results extend the mutational spectrum of HCM and contribute in defining the molecular pathogenesis and inheritance pattern(s) of this condition. Besides, we delineate a specific procedure for the identification of the most likely pathogenetic variants for a next generation sequencing approach embodied in a clinical context

Electrochemical and Spectroscopic Study of Mononuclear Ruthenium Water Oxidation Catalysts: A Combined Experimental and Theoretical Investigation

Solid state NMR/Biophysical Organic Chemistr

BUILDING BRIDGES FOR INNOVATION IN AGEING : SYNERGIES BETWEEN ACTION GROUPS OF THE EIP ON AHA

The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).Peer reviewe

A kinetic, spectral and theoretical investigation on the role of oxygen in the radiolytic oxidation of a sorbityl cyclic acetal

Oxidation of sorbityl furfural induced by radiolytically produced OH radical in the presence of oxygen shows two competing reaction paths, which both preserve the acetal ring. Peroxidation of the hydroxylated furanic ring mantains the ring structure through HO2 elimination, while peroxidation of the pseudo allylic radical leads to a tetroxide, which undergoes a Russel mechanism. Ab-initio and semiempirical computations allow to rationalize the proposed reaction routes

Reactivity of hypotaurine and cysteine sulfinic acid toward carbonate radical anion and nitrogen dioxide as explored by the peroxidase activity of Cu,Zn superoxide dismutase and by pulse radiolysis

Hypotaurine and cysteine sulfinic acid are known to be readily oxidized to the respective sulfonates, taurine and cysteic acid, by several oxidative agents that may be present in biological systems. In this work, the relevance of both the carbonate anion and nitrogen dioxide radicals in the oxidation of hypotaurine and cysteine sulfinic acid has been explored by the peroxidase activity of Cu,Zn superoxide dismutase (SOD) and by pulse radiolysis. The extent of sulfinate oxidation induced by the system SOD/Hydrogen Peroxide in the presence of bicarbonate (Carbonate anion radical generation), or nitrite (Nitrogen dioxide radical generation) has been evaluated. Hypotaurine is efficiently oxidized by the carbonate radical anion generated by the peroxidase activity of Cu,Zn SOD. Pulse radiolysis studies have shown that the carbonate radical anion reacts with hypotaurine more rapidly than nitrogen dioxide. Regarding cysteine sulfinic acid, it is less reactive with the carbonate radical anion than hypotaurine. It has also been observed that the one-electron transfer oxidation of both sulfinates by the radicals is accompanied by the generation of transient sulfonyl radicals. Considering that the carbonate radical anion could be formed in vivo at high level from bicarbonate, this radical can be included in the oxidants capable of performing the last metabolic step of taurine biosynthesis. Moreover, the protective effect exerted by hypotaurine and cysteine sulfinate on the carbonate radical anion-mediated tyrosine dimerization indicates that both sulfinates have scavenging activity towards the carbonate radical anion. However, the formation of transient reactive intermediates during sulfinate oxidation by carbonate anion and nitrogen dioxide radical may at the same time promote oxidative reactions.Hypotaurine and cysteine sulfinic acid are known to be readily oxidized to the respective sulfonates, taurine and cysteic acid, by several oxidative agents that may be present in biological systems. In this work, the relevance of both the carbonate anion and nitrogen dioxide radicals in the oxidation of hypotaurine and cysteine sulfinic acid has been explored by the peroxidase activity of Cu,Zn superoxide dismutase (SOD) and by pulse radiolysis. The extent of sulfinate oxidation induced by the system SOD/Hydrogen Peroxide in the presence of bicarbonate (Carbonate anion radical generation), or nitrite (Nitrogen dioxide radical generation) has been evaluated. Hypotaurine is efficiently oxidized by the carbonate radical anion generated by the peroxidase activity of Cu,Zn SOD. Pulse radiolysis studies have shown that the carbonate radical anion reacts with hypotaurine more rapidly than nitrogen dioxide. Regarding cysteine sulfinic acid, it is less reactive with the carbonate radical anio

Physical exercise, depression, and anxiety in 2190 affective disorder subjects

Background: This study evaluated associations of PE with symptomatic status in mood and anxiety disorder subjects, and considered many other associated factors so as to expand on comparable previous studies. Methods: Consenting adults at a mood disorder center were assessed for associations of PE frequency ([never, past only, ≤once/week] vs. regularly at 2–3- or >3-times/week) with standard psychometric measures of depression and anxiety symptoms, selected demographic, clinical factors, using bivariate and multivariate methods. Results: Of 2190 subjects (58.8% women; mean age 42.6 years; 44.8% with major depressive, 40.6% bipolar, and 14.6% anxiety disorders), 22.5% currently engaged in regular PE. Such engagement was associated with lower morbidity ratings, youth, male sex, being unmarried, more education, higher socio-economic status (SES), less religious practice, less early abuse, younger age at illness onset and at intake, fewer years ill, lower BMI, fewer siblings, hyperthymic temperament, less time depressed before intake, and living at higher population density. Greater PE-frequency was associated with lower ratings of depression (but not anxiety), male sex, younger age, and lower BMI. Factors independently associated with PE in multivariate modeling ranked by significance: older age at intake ≥ lower BMI > more education > higher SES > male sex. Limitations: PE assessment did not include type, intensity or duration. Some information provided may be subject to recall bias, though it should not affect comparisons among subjects. Conclusion: Regularly repeated PE again appeared to be beneficial for patients with depression or anxiety and should be included in their treatment interventions

The chemistry of precipitation and groundwater in a coastal Pinus Pinea forest (Castel Fusano area, central Italy) and its relation to stand and canopy structure

Chloride and sodium contents of net precipitation (throughfall + stemflow) and groundwater below a Pinus Pinea coastal forest (Castel Fusano, central Italy) are strongly dependent on the barrier-effect accomplished by canopies to the wind-transported sea salt aerosol. During dry periods, forest canopy holds marine aerosol, successively discharged by rainfall: the longer the dry period, the higher the amount of salts accumulated and released to groundwater. Main winds direction and regimes of precipitation are important variables influencing the chemistry of net precipitation and groundwater. Stemflow is a point-source input and its contribution to groundwater recharge and chemistry is spatially relevant, even if it represents only a small fraction of net precipitation. Chloride and sodium concentration of stemflow and groundwater was very high in the portion of the forest directly exposed to sea winds and decreased progressively at increasing distances from the coastline. The drop was very marked just few tenths of metres from the forest face and the rate of reduction was less significant further inland, where below-canopy enrichment was negligible. Stand and canopy structure differences within the forest (created by a wild fire occurred in the year 2000 and by successive localised practices of forest thinning) had strong effects onto chloride and sodium contents of stemflow and groundwater. On the contrary, chloride and sodium abundance of throughfall was not notably influenced by precipitation regimes and by stand structure, being a diffuse input to ground, only moderately intercepted by canopies. However, forest thinning increased volumes of throughfall

The chemistry of precipitatios and grounwater in a coastal Pinus Pinea forest (Castel Fusano area, central Italy) and its relations to stand and canopy structure

Chloride and sodium contents of net precipitation (throughfall + stemflow) and groundwater below a Pinus Pinea coastal forest (Castel Fusano, central Italy) are strongly dependent on the barrier-effect accomplished by canopies to the wind-transported sea salt aerosol. During dry periods, forest canopy holds marine aerosol, successively discharged by rainfall: the longer the dry period, the higher the amount of salts accumulated and released to groundwater. Main winds direction and regimes of precipitation are important variables influencing the chemistry of net precipitation and groundwater. Stemflow is a point-source input and its contribution to groundwater recharge and chemistry is spatially relevant, even if it represents only a small fraction of net precipitation. Chloride and sodium concentration of stemflow and groundwater was very high in the portion of the forest directly exposed to sea winds and decreased progressively at increasing distances from the coastline. The drop was very marked just few tenths of metres from the forest face and the rate of reduction was less significant further inland, where below-canopy enrichment was negligible. Stand and canopy structure differences within the forest (created by a wild fire occurred in the year 2000 and by successive localised practices of forest thinning) had strong effects onto chloride and sodium contents of stemflow and groundwater. On the contrary, chloride and sodium abundance of throughfall was not notably influenced by precipitation regimes and by stand structure, being a diffuse input to ground, only moderately intercepted by canopies. However, forest thinning increased volumes of throughfall