Oculofacial alterations in NBAS-SOPH like mutations: Case report

PURPOSE:: To describe the clinical features of a rare case of NBAS-SOPH-like mutations; to emphasize special aspects of the ocular and oro-facial regions. METHODS:: Case report. CASE DESCRIPTION:: We present a 5-year-old girl initially examined for her dysmorphic features, mental delay, strabismus, and high myopia. During the funduscopic examination, we observed optic atrophy with narrow thinned arterioles with the light brown reflex of the central retina. A genetic assessment revealed NBAS-SOPH like mutation. An assessment by a team of orthodontists defined typical characteristics. CONCLUSIONS:: NBAS mutations can also cause complex disease with a broad clinical spectrum ranging from isolated recurrent acute liver failure (RALF) to a multisystemic phenotype. Due to the heterogeneity of the expressions, a multispeciality approach to this situation is recommended

Highly Sulfated K5 Escherichia coli Polysaccharide Derivatives Inhibit Respiratory Syncytial Virus Infectivity in Cell Lines and Human Tracheal-Bronchial Histocultures.

Respiratory syncytial virus (RSV) exploits cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The interaction between RSV and HSPGs thus presents an attractive target for the development of novel inhibitors of RSV infection. In this study, selective chemical modification of the Escherichia coli K5 capsular polysaccharide was used to generate a collection of sulfated K5 derivatives with a backbone structure that mimics the heparin/heparan sulfate biosynthetic precursor. The screening of a series of N-sulfated (K5-NS), O-sulfated (K5-OS), and N,O-sulfated (K5-N,OS) derivatives with different degrees of sulfation revealed the highly sulfated K5 derivatives K5-N,OS(H) and K5-OS(H) to be inhibitors of RSV. Their 50% inhibitory concentrations were between 1.07 nM and 3.81 nM in two different cell lines, and no evidence of cytotoxicity was observed. Inhibition of RSV infection was maintained in binding and attachment assays but not in preattachment assays. Moreover, antiviral activity was also evident when the K5 derivatives were added postinfection, both in cell-to-cell spread and viral yield reduction assays. Finally, both K5-N,OS(H) and K5-OS(H) prevented RSV infection in human-derived tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly differentiated model of the epithelial tissue of the human respiratory tract. Together, these features put K5-N,OS(H) and K5-OS(H) forward as attractive candidates for further development as RSV inhibitors

Evaluation of two lyophilized molecular assays to rapidly detect foot-and-mouth disease virus directly from clinical samples in field settings

Accurate, timely diagnosis is essential for the control, monitoring and eradication of foot‐and‐mouth disease (FMD). Clinical samples from suspect cases are normally tested at reference laboratories. However, transport of samples to these centralized facilities can be a lengthy process that can impose delays on critical decision making. These concerns have motivated work to evaluate simple‐to‐use technologies, including molecular‐based diagnostic platforms, that can be deployed closer to suspect cases of FMD. In this context, FMD virus (FMDV)‐specific reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) and real‐time RT‐PCR (rRT‐PCR) assays, compatible with simple sample preparation methods and in situ visualization, have been developed which share equivalent analytical sensitivity with laboratory‐based rRT‐PCR. However, the lack of robust ‘ready‐to‐use kits’ that utilize stabilized reagents limits the deployment of these tests into field settings. To address this gap, this study describes the performance of lyophilized rRT‐PCR and RT‐LAMP assays to detect FMDV. Both of these assays are compatible with the use of fluorescence to monitor amplification in real‐time, and for the RT‐LAMP assays end point detection could also be achieved using molecular lateral flow devices. Lyophilization of reagents did not adversely affect the performance of the assays. Importantly, when these assays were deployed into challenging laboratory and field settings within East Africa they proved to be reliable in their ability to detect FMDV in a range of clinical samples from acutely infected as well as convalescent cattle. These data support the use of highly sensitive molecular assays into field settings for simple and rapid detection of FMDV

Calibrating accelerometer tags with oxygen consumption rate of rainbow trout (Oncorhynchus mykiss) and their use in aquaculture facility: A case study

SIMPLE SUMMARY: Measuring metabolic rates in free-swimming fish would provide valuable insights about the energetic costs of different life activities this is challenging to implement in the field due to the difficulty of performing such measurements. Thus, the calibration of acoustic transmitters with the oxygen consumption rate (MO(2)) could be promising to counter the limitations observed in the field. In this study, calibrations were performed in rainbow trout (Oncorhynchus mykiss), and a subsample of fish was implanted with such a transmitter and then followed under aquaculture conditions. The use of acoustic transmitters calibrated with MO(2) appeared to be a promising tool to estimate energetic costs in free-swimming rainbow trout, and for welfare assessment in the aquaculture industry. ABSTRACT: Metabolic rates are linked to the energetic costs of different activities of an animal’s life. However, measuring the metabolic rate in free-swimming fish remains challenging due to the lack of possibilities to perform these direct measurements in the field. Thus, the calibration of acoustic transmitters with the oxygen consumption rate (MO(2)) could be promising to counter these limitations. In this study, rainbow trout (Oncorhynchus mykiss Walbaum, 1792; n = 40) were challenged in a critical swimming test (U(crit)) to (1) obtain insights about the aerobic and anaerobic metabolism throughout electromyograms; and (2) calibrate acoustic transmitters’ signal with the MO(2) to be later used as a proxy of energetic costs. After this calibration, the fish (n = 12) were implanted with the transmitter and were followed during ~50 days in an aquaculture facility, as a case study, to evaluate the potential of such calibration. Accelerometer data gathered from tags over a long time period were converted to estimate the MO(2). The MO(2) values indicated that all fish were reared under conditions that did not impact their health and welfare. In addition, a diurnal pattern with higher MO(2) was observed for the majority of implanted trout. In conclusion, this study provides (1) biological information about the muscular activation pattern of both red and white muscle; and (2) useful tools to estimate the energetic costs in free-ranging rainbow trout. The use of acoustic transmitters calibrated with MO(2), as a proxy of energy expenditure, could be promising for welfare assessment in the aquaculture industry

A SAT-based System for Consistent Query Answering

An inconsistent database is a database that violates one or more integrity constraints, such as functional dependencies. Consistent Query Answering is a rigorous and principled approach to the semantics of queries posed against inconsistent databases. The consistent answers to a query on an inconsistent database is the intersection of the answers to the query on every repair, i.e., on every consistent database that differs from the given inconsistent one in a minimal way. Computing the consistent answers of a fixed conjunctive query on a given inconsistent database can be a coNP-hard problem, even though every fixed conjunctive query is efficiently computable on a given consistent database. We designed, implemented, and evaluated CAvSAT, a SAT-based system for consistent query answering. CAvSAT leverages a set of natural reductions from the complement of consistent query answering to SAT and to Weighted MaxSAT. The system is capable of handling unions of conjunctive queries and arbitrary denial constraints, which include functional dependencies as a special case. We report results from experiments evaluating CAvSAT on both synthetic and real-world databases. These results provide evidence that a SAT-based approach can give rise to a comprehensive and scalable system for consistent query answering.Comment: 25 pages including appendix, to appear in the 22nd International Conference on Theory and Applications of Satisfiability Testin

Assessing fish–fishery dynamics from a spatially explicit metapopulation perspective reveals winners and losers in fisheries management

Sustainable management of living resources must reconcile biodiversity conservation and socioeconomic viability of human activities. In the case of fisheries, sustainable management design is made challenging by the complex spatiotemporal interactions between fish and fisheries. We develop a comprehensive metapopulation framework integrating data on species life-history traits, connectivity and habitat distribution to identify priority areas for fishing regulation and assess how management impacts are spatially distributed. We trial this approach on European hake fisheries in the north-western Mediterranean, where we assess area-based management scenarios in terms of stock status and fishery productivity to prioritize areas for protection. Model simulations show that local fishery closures have the potential to enhance both spawning stock biomass and landings on a regional scale compared to a status quo scenario, but that improving protection is easier than increasing productivity. Moreover, the interaction between metapopulation dynamics and the redistribution of fishing effort following local closures implies that benefits and drawbacks are heterogeneously distributed in space, the former being concentrated in the proximity of the protected site. A network analysis shows that priority areas for protection are those with the highest connectivity (as expressed by network metrics) if the objective is to improve the spawning stock, while no significant relationship emerges between connectivity and potential for increased landings. Synthesis and applications. Our framework provides a tool for (1) assessing area-based management measures aimed at improving fisheries outcomes in terms of both conservation and socioeconomic viability and (2) describing the spatial distribution of costs and benefits, which can help guide effective management and gain stakeholder support. Adult dispersal remains the main source of uncertainty that needs to be investigated to effectively apply our model to fisheries regulation

Poly(amidoamine)-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System

A new poly(amidoamine)-cholesterol (PAA-cholesterol) conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step

Oral sodium butyrate supplementation ameliorates paclitaxel-induced behavioral and intestinal dysfunction

Paclitaxel (PTX) is one of the most broadly used chemotherapeutic agents for the treatment of several tumor types including ovarian, breast, and non-small cell lung cancer. However, its use is limited by debilitating side effects, involving both gastrointestinal and behavioral dysfunctions. Due to growing evidence showing a link between impaired gut function and chemotherapy-associated behavioral changes, the aim of this study was to identify a novel therapeutic approach to manage PTX-induced gut and brain comorbidities. Mice were pre-treated with sodium butyrate (BuNa) for 30 days before receiving PTX. After 14 days, mice underwent to behavioral analysis and biochemical investigations of gut barrier integrity and microbiota composition. Paired evaluations of gut functions revealed that the treatment with BuNa restored PTX-induced altered gut barrier integrity, microbiota composition and food intake suggesting a gut-to-brain communication. The treatment with BuNa also ameliorated depressive- and anxiety-like behaviors induced by PTX in mice, and these effects were associated with neuroprotective and anti-inflammatory outcomes. These results propose that diet supplementation with this safe postbiotic might be considered when managing PTX-induced central side effects during cancer therapy