Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family

Intellectual disability (ID) is the term used to describe a diverse group of neurological conditions with congenital or juvenile onset, characterized by an IQ score of less than 70 and difficulties associated with limitations in cognitive function and adaptive behavior. The condition can be inherited or caused by environmental factors. The genetic forms are heterogeneous, with mutations in over 500 known genes shown to cause the disorder. We report a consanguineous Omani family in which multiple individuals have ID and developmental delay together with some variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the toes or hands. Homozygosity mapping combined with whole exome next generation sequencing identified a novel homozygous single base pair deletion in TUSC3, c.222delA, p.R74 fs. The mutation segregates with the disease phenotype in a recessive manner and is absent in 60,706 unrelated individuals from various disease-specific and population genetic studies. TUSC3 mutations have been previously identified as causing either syndromic or non-syndromic ID in patients from France, Italy, Iran and Pakistan. This paper supports the previous clinical descriptions of the condition caused by TUSC3 mutations and describes the seventh family with mutations in this gene, thus contributing to the genetic spectrum of mutations. This is the first report of a family from the Arabian peninsula with this form of ID

COMPETITION AMONG HOSPITALS AND ITS MEASUREMENT: THEORY AND A CASE STUDY

Our paper provides several insights on the characteristics of the concept of “Poles d’Excellence Rurale” (PER) through bilateral comparisons with that of Competitive Pole (CP) and cluster. The concept of PER is a French government’ initiative designed for the development of rural areas similar to that of the Competitive Pole. We emphasize important particularities of these concepts by analyzing some of their similarities and major differences.Pole d’Excellence Rurale, Competitive Pole, cluster, rural development

Identification of 31 genomic loci for autosomal recessive mental retardation and molecular genetic characterization of novel causative mutations in four genes.

Severe mental and behavioral disorders are common, affecting 1-3% of the world populace. They thus constitute a major burden not only for the affected families but also for society. There is reason to believe that autosomal recessive mental retardation (ARMR) is more common than X-linked MR, but it has so far received considerably less attention. This is partly due to small family sizes and low consanguinity rates in industrialized societies, both of which have hampered gene mapping and identification, which is illustrated by the fact that until 2003, when this study was started, no more than one gene was shown to be implicated in non-syndromic ARMR (NS-ARMR). The work presented here is part of a larger project to shed more light on the molecular causes of ARMR as a prerequisite for diagnosis, counselling and therapy, focusing on large consanguineous Iranian families with several mentally retarded children. It combines clinical and molecular approaches such as patient recruitment, clinical characterization, sample collection, SNP array genotyping, whole genome linkage analysis, homozygosity mapping and finally mutation screening in a systematic fashion. Successful mutation detection is followed by functional analyses of the affected genes. In the study presented here, the investigation of 135 families led to the identification of 31 novel genomic loci for ARMR. Contrary to previous observations, which prima facie argued against the existence of frequently mutated genes, overlapping autozygosity regions from several families could now be observed on chromosomes 1, 5 and 19. At each of these loci a minimum of two overlapping linkage intervals were solitary in the respective families and showed a LOD score of, or above, three. Mutation screening in one of these families with NS-ARMR has led to the discovery of a new gene for NS-ARMR, TUSC3, where a mutation was found that leads to the loss of TUSC3 transcript in patient cells. Additional investigations in families with syndromic forms of ARMR revealed a new gene for ataxia and mild mental retardation. This gene, CA8, was found to carry a R237Q mutation, with a putatively deleterious effect on functional properties of the gene product in the affected patients. Furthermore one novel mutation in ALDH3A2 in patients with Sjögren-Larsson syndrome and two in the MCPH1 gene in patients with primary microcephaly were found. Gene expression profiling, knockdown experiments and irradiation studies added more evidence on the involvement of MCPH1 in cell cycle control, DNA damage response and transcriptional regulation. In summary, the identification of a novel gene for NS-ARMR and many new genomic intervals with a high probability for containing different genes with disease causing mutations is in keeping with previous results that indicated a high degree of genetic heterogeneity for this disorder. Still, the several overlapping loci found in this study now also indicate the presence of genes with an increased frequency of mutations in ARMR patients. Further studies are necessary to identify the disease causing mutations in these newly identified linkage intervals and to determine the contribution of the affected genes to the complex processes of human cognition. These studies will be greatly facilitated by the novel high throughput sequencing technologies, which are now available and that will allow a much increased pace for the detection of disease causing mutations

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Evaluation of Coastal Protection Mentions Methods and Design of Protection Structures

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Direct operational matrix approach for weakly singular Volterra integro-differential equations: application in theory of anomalous diffusion

In the current paper, we present an efficient direct scheme for weakly singular Volterra integro-differential equations arising in the theory of anomalous diffusion. The behavior of the system demonstrating the anomalous diffusion is significant for small times. The method is based on operational matrices of Chebyshev and Legendre polynomials with some techniques to reduce the total errors of the already existing schemes. The proposed scheme converts these equations into a linear system of algebraic equations. The main advantages of the method are high accuracy, simplicity of performing, and low storage requirement. The main focus of this study is to obtain an analytical explicit expression to estimate the error. Numerical results confirm the superiority and applicability of our scheme in comparison with other methods in the literature

Evaluating knowledge, attitude and practice of Health-Care Workers regarding patient education in Iran

The objective of the study was to evaluate the position of patient education measuring knowledge, attitude, and practice (KAP) among health care workers (HCWs). It is also aimed to emphasize the need for a real position for patient education. This survey was performed among a group of HCWs in Iran. The scores had an acceptable level. However, nurses, females and younger people received higher scores. The staff was already aware of patient education necessity and considered it as the duty of all medical team. Often HCWs cannot include patient education in their routine due to time shortage, lack of staff�s financial motivation, fatigue, and loads of work, etc. There is still need for a real training in the educational curriculum. Additionally, the various HCWs�related obstacles should be taken into account. © 2015 Tehran University of Medical Sciences. All rights reserved

Development and testing of advanced nano-scale fluorescent materials for urban heat mitigation

Urban heat effect is a serious environmental issue impacting many big cities around the world. One of the main factors contributing to the urban overheating are highly absorptive construction materials such as asphalt and concrete. The literature shows that the existing urban mitigation techniques including greeneries, water-based technologies, and available heat-rejecting materials are not capable of addressing the future urban overheating intensity, and therefore, it is essential to develop more efficient urban mitigation technologies with higher cooling potential. In addition, some cities have harsh climate conditions in both summer and winter, and as a result, adaptive technologies such as temperature-sensitive/thermochromic coating materials for reducing the energy needs during the whole year should be developed. In this context, nano-scale fluorescent materials (quantum dots (QDs)) as novel heat-rejecting materials for mitigation of the urban overheating are developed and their cooling potential for the urban heat mitigation is estimated in this research. The developed QDs-based coatings have two main characteristics making them ideal heat-rejecting material for the urban heat mitigation application. The two major features of QDs include: 1. Tuneable fluorescent properties due to quantum confinement effect at nanoscale, 2. High transmission of QDs as semiconductors at wavelengths longer than their absorption edge band. In this research, for the very first time, a novel mathematical model for the optimization of the fluorescent cooling and calculation of non-radiative losses is developed. The most effective methods for enhancing the fluorescent cooling potential were then proposed according to the fluorescent cooling model estimations. This research reports some experimental work on reducing the thermal loss in QDs-based films. In addition to that, a novel bilayer supercool material composed of a fluorescent material and a near-infrared (NIR)-reflective material was proposed. The bilayer fluorescent-NIR-reflective materials works based on the high transmission of the QDs as top layer and high reflection of the NIR-reflective material at wavelengths longer than the absorption edge of the QDs material. As for the climates with extreme weather conditions during winter and summer, the recent developments on dye-based temperature-sensitive/thermochromic materials for building application were reviewed. The main issue for their real application was discussed, and alternative thermochromic technologies for the building application were identified. In particular, the temperature-sensitive properties of QDs-based coatings were described in detail. An extended version of the fluorescent cooling algorithm was developed to study the cooling and heating performance of temperature-sensitive fluorescent materials during hot and cold seasons

Analysis of congenital disorder of glycosylation-Id in a yeast model system shows diverse site-specific under-glycosylation of glycoproteins

Asparagine-linked glycosylation is a common post translational modification of proteins in eukaryotes. Mutations in the human ALG3 gene cause changed levels and altered glycan structures on mature glycoproteins and are the cause of a severe congenital disorder of glycosylation (CDG-Id). Diverse glycoproteins are also under-glycosylated in Saccharomyces cerevisae alg3 mutants. Here we analyzed site-specific glycosylation occupancy in this yeast model system using peptide-N-glycosidase F to label glycosylation sites with an asparagine-aspartate conversion that creates a new endoproteinase AspN cleavage site, followed by proteolytic digestion, and detection of peptides and glycopeptides by LC-ESI-MS/MS. We used this analytical method to identify and measure site specific glycosylation occupancy in alg3 mutant and wild type yeast strains. We found decreased site specific N-glycosylation occupancy in the alg3 knockout strain preferentially at Asn-Xaa-Ser sequences located in secondary structural elements, features previously associated with poor glycosylation efficiency. Furthermore, we identified 26 previously experimentally unverified glycosylation sites. Our results provide insights into the underlying mechanisms of disease in CDG-Id, and our methodology will be useful in site specific glycosylation analysis in many model systems and clinical applications