Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction : Atomistic characterization of a Rett syndrome causing mutation

Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies. Herein, we use molecular dynamics simulations to obtain a detailed view of the dynamics of WT and mutated MBD in the presence and absence of DNA. The pathogenic mutation Y120D is used as paradigm for our studies. Further, since the Y120 residue was previously found to be a phosphorylation site, we characterize the dynamic profile of the MBD also in the presence of Y120 phosphorylation (pY120). We found that addition of a phosphate group to Y120 or mutation in aspartic acid affect domain mobility that samples an alternative conformational space with respect to the WT, leading to impaired ability to interact with DNA. Experimental assays showing a significant reduction in the binding affinity between the mutated MBD and the DNA confirmed our predictions

Mesalamine-induced myopericarditis in children: a case report and a short revision of the literature

Mesalamine has a central role in the treatment of inflammatory bowel disease (IBD). Myocarditis and/or pericarditis are rare and severe side effects of mesalamine-containing drugs. We describe the case of a 14 years old boy, developing myopericarditis two weeks after starting mesalamine treatment for ulcerative colitis (UC). The adverse effect had a massive impact on the left ventricular function and required immedi-ate intervention. Once identified as possible causative agent, mesalamine was discontinued with subsequent improvement of the clinical symptoms and laboratory findings. No recurrency nor sequelae were detected at the cardiological follow up. Mesalamine is a widely used drug for pediatric IBD treatment, although its effect on heart tissues is a rare but potentially fatal adverse reaction. At the time of presentation, in April 2021, 10 pediatric cases were reported in literature (2 children and 8 adolescents). Of them, 60% were treated with me-salamine for UC and 40% for Chron’s disease (CD). Chest pain and fever were the most common symptoms at presentation (100% and 50% respectively), cough and fatigue were less represented. None of the patients developed sequelae at follow up. In patients treated with mesalamine early recognition of side effects, drug discontinuation and accurate therapy are crucial to prevent progression of the inflammation and to avoid adverse cardiovascular outcomes. (www.actabiomedica.it)

The self-aggregation of porphyrins with multiple chiral centers in organic/aqueous media: the case of sugar: the steroid-porphyrin conjugates

An overview of the solvent-driven aggregation of a series of chiral porphyrin derivatives studied by optical methods (uv/vis, fluorescence, cd and rls spectroscopies) is herein reported; the investigated porphyrins are characterized by the presence in the meso-positions of glycol-, steroidal- and glucosteroidal moieties, conferring amphiphilicity and solubility in aqueous media to the primarily hydrophobic porphyrin platform. Aggregation of the macrocycles is driven by a change in bulk solvent composition, forming architectures with supramolecular chirality, steered by the stereogenic centers on the porphyrin peripheral positions. The aggregation behavior and chiroptical properties of the final aggregated species strongly depend on the number and stereogenicity of the ancillary groups that dictate the mutual spatial arrangement of the porphyrin chromophores and their further organization in larger structures, usually detectable by different microscopies, such as AFM and SEM. Kinetic studies are fundamental to understand the aggregation mechanism, which is frequently found to be dependent on the substrate concentration. Additionally, Molecular Mechanics calculations can give insights into the intimate nature of the driving forces governing the self-assembly process. The critical use of these combined methods can shed light on the overall self-assembly process of chirally-functionalized macrocycles, with important implications on the development of chiral porphyrin-based materials

Chiral recognition with broad selective sensor arrays

The detection and discrimination of chiral analytes has always been a topical theme in food and pharmaceutical industries and environmental monitoring, especially when dealing with chiral drugs and pesticides, whose enantiomeric nature assessment is of crucial importance. The typical approach matches novel chiral receptors designed ad hoc for the discrimination of a target enantiomer with emerging nanotechnologies. The massive synthetic efforts requested and the difficulty of analyzing complex matrices warrant the ever-growing exploitation of sensor array as an alternative route, using a limited number of chiral or both chiral and achiral sensors for the stereoselective identification and dosing of chiral compounds. This review aims to illustrate a little-explored winning strategy in chiral sensing based on sensor arrays. This strategy mimics the functioning of natural olfactory systems that perceive some couples of enantiomeric compounds as distinctive odors (i.e., using an array of a considerable number of broad selective receptors). Thus, fundamental concepts related to the working principle of sensor arrays and the role of data analysis techniques and models have been briefly presented. After the discussion of existing examples in the literature using arrays for discriminating enantiomers and, in some cases, determining the enantiomeric excess, the remaining challenges and future directions are outlined for researchers interested in chiral sensing applications

Benefits and medium-term outcome of the Sorin Pericarbon Freedom stentless aortic prosthesis in cases of acute bacterial endocarditis

OBJECTIVES The aim of this study is to evaluate the ease of use and the advantages of Sorin Pericarbon Freedom (SPF) stentless valve in cases of acute bacterial endocarditis and to check the intermediate-term results after the implant of SPF with respect to resistance to infection, valve deterioration and durability. METHODS Between June 2003 and February 2015, 26 patients with active aortic valve bacterial endocarditis underwent aortic valve replacement with SPF pericardial stentless aortic prosthesis. The mean age was 57 \ub1 18 years; 73% of the patients were in preoperative NYHA class III and VI. Mean Logistic EuroSCORE was 14.2 \ub1 12.7. Endocarditis occurred in 18 patients with native valves, and in 9 patients with prosthetic valves (4 mechanical aortic valve prostheses; 5 aortic bioprostheses). Aortic root abscesses were observed in 16 cases (61.5%). Surgery was emergent in 3 cases (11.5%). Redo surgery was performed in 9 cases (35%). Cumulative follow-up was 126.8 patient-years (mean 4.9 \ub1 3.3 years). RESULTS Operative hospital mortality was 0% for all patients. Residual mean prosthetic gradient at discharge was 9.4 \ub1 3.6 mmHg. Neither residual aortic incompetence nor residual abscess cavity was observed at discharge. Mean ejection fraction at discharge was 54 \ub1 8% (Min; Max: 35%; 65%). A total of 4 patients died at follow-up, all for non-cardiac causes. One patient was lost to follow-up. Two patients (8%) underwent non-valve-related reoperation with 0% mortality. Residual mean gradient at follow-up was 7.2 \ub1 2.1 mmHg. Three patients (17%) presented with mild/moderate aortic incompetence and 89% of patients were in NYHA Class I-II at follow-up. At 9 years, actuarial freedom from valve-related reoperation and from structural valve deterioration was 100%. CONCLUSIONS The SPF aortic prosthesis is a true pericardial stentless prosthesis suitable for the treatment of acute bacterial endocarditis. Intermediate-time results in terms of freedom from reoperation, structural valve deterioration and resistance to infections are satisfactory. Haemodynamic performances are excellent since a complete exclusion of aortic root abscesses is achieved without any reduction of the aortic annular diameter, usually due to marsupialization or patch closure of the infected cavities

Proline enantiomers discrimination by (L)-prolinated porphyrin derivative Langmuir-Schaefer films: proof of concept for chiral sensing applications

A porphyrin derivative functionalized with the L-enantiomer of proline amino acid was characterized at the air-pure water interface of the Langmuir trough. The porphyrin derivative was dissolved in dichloromethane solution, spread at the air-subphase interface and investigated by acquiring the surface pressure vs. area per molecule Langmuir curves. It is worth observing that the behavior of the molecules of the porphyrin derivative floating film was substantially influenced by the presence of L-proline amino acid dissolved in the subphase (10(-5) M); on the contrary, the physical chemical features of the floating molecules were only slightly influenced by the D-proline dissolved in the subphase. Such an interesting chirality-driven selection was preserved when the floating film was transferred onto solid supports by means of the Langmuir-Schaefer method, but it did not emerge when a spin-coating technique was used for the layering of the tetrapyrrolic derivatives. The obtained results represent proof of concept for the realization of active molecular layers for chiral discrimination: porphyrin derivatives, due to their intriguing spectroscopic and supramolecular properties, can be functionalized with the chiral molecule that should be detected. Moreover, the results emphasize the crucial role of the deposition technique on the features of the sensing layers

Relevance of the Operator’s Experience in Conditioning the Static Computer-Assisted Implantology: A Comparative In Vitro Study with Three Different Evaluation Methods

The present study aimed to evaluate the influence of manual expertise on static computer-aided implantology (s-CAI) in terms of accuracy and operative timings. After the cone-beam CT (CBCT) scanning of eleven mandibular models, a full-arch rehabilitation was planned, and two different skilled operators performed s-CAI. The distances between the virtual and actual implant positions were calculated considering the three spatial vectorial axes and the three-dimensional Euclidean value for the entry (E) and apical (A) points, along with the axis orientation differences (Ax). These values emerged from the overlapping of the pre-op CBCT to post-op CBCT data (method 1), from scanning the data from the laboratory scanner (method 2), and from the intra-oral scanner (method 3) and were correlated with the operators’ expertise and operative timings. The mean values for accuracy from the three methods were: E = 0.57 (0.8, 0.45, 0.47) mm, A = 0.6 (0.8, 0.48, 0.49) mm, and Ax 1.04 (1.05,1.03,1.05) ° for the expert operator; and E = 0.8 (0.9, 0.87, 0.77), A = 0.95 (1.02, 0.95, 0.89), and Ax =1.64 (1.78, 1.58, 1.58) for the novice. The mean value of the operative timings was statistically inferior for the expert operator (p < 0.05), with an improved accuracy over time for both operators. A significant difference (p < 0.05) emerged between method 1 and methods 2 and 3 for seven of the nine variables, without differences between the evaluations from the two scanners. The support from digital surgical guides does not eliminate the importance of manual expertise for the reliability and the shortening of the surgical procedure, and it requires a learning pathway over time

Microgravity vertical gradient measurement in the site of VIRGO interferometric antenna (Pisa plain, Italy)

The site of the European Gravitational Observatory (EGO) located in the countryside near Pisa (Tuscany, Italy) was investigated by a microgravity vertical gradient (MVG) survey. The EGO site houses the VIRGO interferometric antenna for gravitational waves detection. The microgravity survey aims to highlight the gravity anomalies of high-frequency related to more superficial geological sources in order to obtain a detailed model of the lithologic setting of the VIRGO site, that will allow an estimate of the noise induced by seismic waves and by Newtonian interference. This paper presents the results of the gradiometric survey of 2006 in the area of the interferometric antenna. MVG measurements allow us to enhance the high frequency signal strongly associated with the shallow structures. The gradient gravity map shows a main negative pattern that seems related to the trending of the high density layer of gravel that was evidenced in geotechnical drillings executed along the orthogonal arms during the construction of the VIRGO complex. Calibrating the relationship between the vertical gradient and the depth of the gravel interface we have computed a model of gravity gradient for the whole VIRGO site, defining the 3D distribution of the top surface of this layer. This latter shows a NE-SW negative pattern that may represent a palaeo-bed alluvial of the Serchio from the Bientina River system

Environmental magneto-gradiometric marine survey in high anthropic noisy area

We describe the magneto-gradiometric survey performed in the Mar Piccolo of Taranto, Italy in May 2005 for environmental aims. This region, being a noisy harbour environment, provides a challenging test for magnetic methods. To reduce the spurious noise signals, both of temporal and spatial origin, we used two Geometrics G880 caesium magnetometers towed in transverse gradient configuration. We show how in shallow waters this gradiometric configuration allows one to distinguish the anomalies due to small metallic bodies near the seafloor from the induced noise due to anthropic contribution and geomagnetic field variations. A direct visual inspection confirmed that the peculiarities highlighted in the gradient anomaly map were due to abandoned metallic objects founded on the seafloor