Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD—both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.     

The effect of strength and endurance training on gait, balance, fall risk, and health services use in community-living older adults

BACKGROUND: The study tested the effect of strength and endurance training on gait, balance, physical health status, fall risk, and health services use in older adults. METHODS: The study was a single-blinded, randomized controlled trial with intention-to-treat analysis. Adults (n = 105) age 68-85 with at least mild deficits in strength and balance were selected from a random sample of enrollees in a health maintenance organization. The intervention was supervised exercise (1-h sessions, three per week, for 24-26 weeks), followed by self-supervised exercise. Exercise groups included strength training using weight machines (n = 25), endurance training using bicycles (n = 25), and strength and endurance training (n = 25). Study outcomes included gait tests, balance tests, physical health status measures, self-reported falls (up to 25 months of follow-up), and inpatient and outpatient use and costs. RESULTS: There were no effects of exercise on gait, balance, or physical health status. Exercise had a protective effect on risk of falling (relative hazard = .53, 95% CI = .30-.91). Between 7 and 18 months after randomization, control subjects had more outpatient clinic visits (p < .06) and were more likely to sustain hospital costs over $5000 (p < .05). CONCLUSIONS: Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults. In community-living adults with mainly mild impairments in gait, balance, and physical health status, short-term exercise may not have a restorative effect on these impairments.     

Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

The enzyme Zmp1 is a zinc‐containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8‐hydroxyquinoline‐2‐hydroxamate scaffold. Among the synthesized compounds, N‐(benzyloxy)‐8‐hydroxyquinoline‐2‐carboxamide ( 1 c ) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte‐derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation.     

Impact of Traffic Management on Black Carbon Emissions: a Microsimulation Study

This paper investigates the effectiveness of traffic management tools, including traffic signal control and en-route navigation provided by variable message signs (VMS), in reducing traffic congestion and associated emissions of CO₂, NO_x, and black carbon. The latter is among the most significant contributors of climate change, and is associated with many serious health problems. This study combines traffic microsimulation (S-Paramics) with emission modeling (AIRE) to simulate and predict the impacts of different traffic management measures on a number traffic and environmental Key Performance Indicators (KPIs) assessed at different spatial levels. Simulation results for a real road network located in West Glasgow suggest that these traffic management tools can bring a reduction in travel delay and BC emission respectively by up to 6 % and 3 % network wide. The improvement at local levels such as junctions or corridors can be more significant. However, our results also show that the potential benefits of such interventions are strongly dependent on a number of factors, including dynamic demand profile, VMS compliance rate, and fleet composition. Extensive discussion based on the simulation results as well as managerial insights are provided to support traffic network operation and control with environmental goals. The study described by this paper was conducted under the support of the FP7-funded CARBOTRAF project.     

Rapid Prototyping of Adaptable User Interfaces

User interface adaptation has been proposed in recent years as a means to achieve personalized accessibility and usability of user interfaces. Related user interface architectures, as well as a variety of related development method and tools, have also been elaborated. Admittedly, however, despite the recognized validity of the approach, which has been proved in practice in a series of prototype systems, the wider adoption and uptake of user interface adaptation approaches are still limited. One of the identified obstacles is the complexity intrinsic in designing such interfaces and the need of radically revising the current user interface design practice to account for (a) the alternative designs required for adaptation, (b) the parameters involved in driving adaptations (i.e., selecting among alternatives at a given point during interaction), and (c) the logic of adaptation at runtime. This article proposes a twofold tool-based support strategy for user interface adaptation development, based on (a) an adaptation development toolkit and related widget library, which directly embeds lexical level adaptations into common interactive widgets, and (b) embedding such a library in a common integrated development environment, thus allowing designers to define and view alternative adaptations at design time and create adaptable user interfaces through traditional prototyping. The aforementioned approach has been implemented in the domain of adaptable applications for older users, producing tools that are currently in use in the development of a large suite of interactive applications in various domains. The approach presented in this article is claimed to be the first and so far unique supporting rapid prototyping of adaptable user interfaces, thus minimizing the divergence between typical development practices and user interface adaptation development.     

Ecotoxicity of naproxen and its phototransformation products

The occurrence of pharmaceuticals in the environment is of great concern and only few data are available about the adverse effects of such molecules and their derivatives on non-target aquatic organisms. This study was designed to assess the toxic potential of Naproxen, a nonsteroidal anti-inflammatory, Naproxen Na, its freely water soluble sodium salt and their photoproducts in the aquatic environment. Bioassays were performed on algae, rotifers and microcrustaceans to assess acute and chronic toxicity. Furthermore, possible genotoxic effects of photoderivatives were investigated using SOS chromotest and Ames fluctuation test. The results showed that photoproducts were more toxic than the parent compounds both for acute and chronic values, while genotoxic and mutagenic effects were not found. These findings suggested the opportunity to consider derivatives in ecotoxicology assessment of drugs.     

Contamination of animal feed and food from animal origin with mineral oil hydrocarbons

Oils and fats used for the production of animal feed can become contaminated with mineral oil material originating from gas oils (C₁₈-C₃₅) or synthetic oils (poly alpha olefins, C₂₅ to beyond C₄₅). An important cause is assumed to be the discharge of waste oils, such as motor oil and hydraulic oils. Mineral oil material was analysed by on-line LC-GC-FID directly in the fat or in a raw extract from animal feed or foodstuffs. In Switzerland in summer/autumn 1999 concentrations in oils and fats for feed production were often found to be between 100 and 1000mg/kg. In the feeds, the average concentration was around 100mg/kg with values ranging up to a maximum of 1000mg/kg; few samples were free of contamination. In animal body fat, the average concentration determined in summer 1999 was 25mg/kg, with a maximum of 150mg/kg, although in samples from December 1999, contamination was substantially lower. In the fat phase of eggs, the average concentration was 30mg/kg, with a maximum of 80mg/kg. Paraffin oil is used for feed production, which may account for part of the contamination problem (e.g. eggs).     

Crisis-driven changes in construction patterns: evidence from building permits in a Mediterranean city

Abstract

This study aimed to describe the construction sector’s response to the 2007–2008 recession based on the spatial analysis of 10 building activity indicators over a 25-year period (1990–2014) in Athens, Greece. Expansion and recession cycles influenced the average values of four indicators (density of new buildings, average floors per new building, density of enlarged buildings and building permits per inhabitant) without altering their spatial pattern. By contrast, the spatial distribution of six indicators (proportion of small-sized dwellings, average surface area of new buildings, average number of floors in enlarged buildings, average surface area of enlarged buildings, volume ratio of enlarged buildings compared to new buildings and ratio of new building surface area to the absolute population increase) became more heterogeneous during the study period. Local-scale indicators derived from building-permits data provide insights into building cycles, shedding light on the short-term effects of the recent crisis on the construction sector.