Clinical guidelines for the management of craniofacial fibrous dysplasia

Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic, activating mutations of the GNAS gene that results in inhibition of the differentiation and proliferation of bone-forming stromal cells and leads to the replacement of normal bone and marrow by fibrous tissue and woven bone. The phenotype is variable and may be isolated to a single skeletal site or multiple sites and sometimes is associated with extraskeletal manifestations in the skin and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and progression of FD may also vary, thereby making the management of this condition difficult with few established clinical guidelines. This paper provides a clinically-focused comprehensive description of craniofacial FD, its natural progression, the components of the diagnostic evaluation and the multi-disciplinary management, and considerations for future research

Weight loss maintenance in women two to eleven years after participating in a commercial program: a survey

BACKGROUND: After 5 years, most reports show that less than 10% of people maintain a 5% loss from initial body weight. Weight maintenance after 10 years is rarely assessed, especially in commercial programs. The current article reports weight maintenance in individuals who had participated 2 to 11 years earlier in a popular commercial weight loss program based on Canada's Food Guide called Mincavi. METHODS: Randomly picked subjects answered a telephone questionnaire. Participants, 291 adult women from various regions of the province of Quebec, had followed the program 2 to 11 years earlier for at least a month. Body weight at the beginning and at the end of treatment was recorded as well as actual weight, age and height. Existing records allowed partial verification of the sample. RESULTS: Based on corrected weights, percentage of women who maintained at least 5% of their initial weight loss are as following; 2 years = 43.6% (n = 55), 3 years = 33.3% (n = 42), 4 years = 23.8% (n = 42), 5–6 years = 38.2% (n = 55), 7–8 years = 29.4% (n = 51), and 9–11 years; 19.6% (n = 46). Five to eleven years after they had participated in the program 29.1% of all women maintained a weight loss of at least 5%, while 14.3% maintained a loss of at least 10%. CONCLUSIONS: Even though success rate is not as high as could be wished for, results show that participation in the Mincavi program can lead to effective weight maintenance long after individuals have left it. These findings suggest more thorough studies should be conducted on this weight loss program

Differences in the experience of fatigue in patients and healthy controls: patients' descriptions

Contains fulltext : 51764.pdf ( ) (Open Access)BACKGROUND: The primary objective was to develop an adjective checklist, the Fatigue Quality List (FQL), aimed at assessing different perceptions of fatigue. METHODS: 961 participants filled out the FQL (28 adjectives). A component and confirmatory factor analyses were performed and psychometric properties were evaluated. Differences on factor scores between different patients' groups were investigated and pre- and post treatment scores were compared in demonstrating change of perceptions after treatment of fatigue. RESULTS: Four independent factors were found with adequate psychometric properties. Different perceptions were found between the patients' groups. Patients who were recovered after treatment for fatigue showed similar scores on the factors as healthy controls. CONCLUSION: The FQL appears to be a promising tool in measuring different perceptions of fatigue, which can be especially interesting for clinical practice

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits

GATA2 monoallelic expression underlies reduced penetrance in inherited GATA2-mutated MDS/AML.

Saudi Arabian Ministry of Higher Education through a doctoral scholarship awarded to A.F.A.S. and a Bloodwise Programme grant (14032) awarded to J.F., T.V., and I.D

Oxidative/Nitrative Stress and Inflammation Drive Progression of Doxorubicin-Induced Renal Fibrosis in Rats as Revealed by Comparing a Normal and a Fibrosis-Resistant Rat Strain

Chronic renal fibrosis is the final common pathway of end stage renal disease caused by glomerular or tubular pathologies. Genetic background has a strong influence on the progression of chronic renal fibrosis. We recently found that Rowett black hooded rats were resistant to renal fibrosis. We aimed to investigate the role of sustained inflammation and oxidative/nitrative stress in renal fibrosis progression using this new model. Our previous data suggested the involvement of podocytes, thus we investigated renal fibrosis initiated by doxorubicin-induced (5 mg/kg) podocyte damage. Doxorubicin induced progressive glomerular sclerosis followed by increasing proteinuria and reduced bodyweight gain in fibrosis-sensitive, Charles Dawley rats during an 8-week long observation period. In comparison, the fibrosis-resistant, Rowett black hooded rats had longer survival, milder proteinuria and reduced tubular damage as assessed by neutrophil gelatinase-associated lipocalin (NGAL) excretion, reduced loss of the slit diaphragm protein, nephrin, less glomerulosclerosis, tubulointerstitial fibrosis and matrix deposition assessed by periodic acid-Schiff, Picro-Sirius-red staining and fibronectin immunostaining. Less fibrosis was associated with reduced profibrotic transforming growth factor-beta, (TGF-beta1) connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL-1a1) mRNA levels. Milder inflammation demonstrated by histology was confirmed by less monocyte chemotactic protein 1 (MCP-1) mRNA. As a consequence of less inflammation, less oxidative and nitrative stress was obvious by less neutrophil cytosolic factor 1 (p47phox) and NADPH oxidase-2 (p91phox) mRNA. Reduced oxidative enzyme expression was accompanied by less lipid peroxidation as demonstrated by 4-hydroxynonenal (HNE) and less protein nitrosylation demonstrated by nitrotyrosine (NT) immunohistochemistry and quantified by Western blot. Our results demonstrate that mediators of fibrosis, inflammation and oxidative/nitrative stress were suppressed in doxorubicin nephropathy in fibrosis-resistant Rowett black hooded rats underlying the importance of these pathomechanisms in the progression of renal fibrosis initiated by glomerular podocyte damage

Association between Acquired Uniparental Disomy and Homozygous Mutations and HER2/ER/PR Status in Breast Cancer

Background: Genetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing. Methods/Principal Findings: We retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. Aupd was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus. Conclusions/Significance: We conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclu

Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model

Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration. In this paper, we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to two-spatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expound how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.PostprintPeer reviewe

Habitat Composition and Connectivity Predicts Bat Presence and Activity at Foraging Sites in a Large UK Conurbation

Background: Urbanization is characterized by high levels of sealed land-cover, and small, geometrically complex, fragmented land-use patches. The extent and density of urbanized land-use is increasing, with implications for habitat quality, connectivity and city ecology. Little is known about densification thresholds for urban ecosystem function, and the response of mammals, nocturnal and cryptic taxa are poorly studied in this respect. Bats (Chiroptera) are sensitive to changing urban form at a species, guild and community level, so are ideal model organisms for analyses of this nature. Methodology/Principal Findings: We surveyed bats around urban ponds in the West Midlands conurbation, United Kingdom (UK). Sites were stratified between five urban land classes, representing a gradient of built land-cover at the 1 km 2 scale. Models for bat presence and activity were developed using land-cover and land-use data from multiple radii around each pond. Structural connectivity of tree networks was used as an indicator of the functional connectivity between habitats. All species were sensitive to measures of urban density. Some were also sensitive to landscape composition and structural connectivity at different spatial scales. These results represent new findings for an urban area. The activity of Pipistrellus pipistrellus (Schreber 1774) exhibited a non-linear relationship with the area of built land-cover, being much reduced beyond the threshold of,60 % built surface. The presence of tree networks appears to mitigate the negative effects of urbanization for this species