Fibrous dysplasia and aneurysmal bone cyst of the skull base presenting with blindness: a report of a rare locally aggressive example

Fibrous dysplasia (FD) and aneurysmal bone cyst (ABC) are uncommon benign intraosseous lesions. Simultaneous occurrence of both lesions is extremely rare. We present an example of concomitant FD and ABC in a 7 year-old with left eye blindness and discharge of one month duration. Physical examination revealed a proptotic left eye and bulging of the hard palate. CT and MRI are consistent with FD and ABC that involved the sphenoid and ethmoidal bones bilaterally. Incomplete combined endonasalcranial resection was performed. The patient presented five months postoperatively with a large recurrence and subsequent follow up was lost. Concomitant FD with ABC may occur in paranasal sinuses and may develop rapidly and exhibit locally aggressive behavior

Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance

BACKGROUND: The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC) is associated with frequent treatment failures (~90% in metastatic cases), and these tumors frequently contain PTEN abnormalities. RESULTS: Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis. CONCLUSION: Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories

Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome

Importance: Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The ε4 allele of the apolipoprotein E gene (APOE ε4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE ε4 genotype is associated with an early cognitive advantage. Here we investigate associations of APOE ε4 with attention across the life span of individuals with DS. Objective: To investigate associations between APOE ε4 and attentional abilities in young children and in adults with DS. Design, Settings, and Participants: In this cross-sectional study, data were collected from 80 young children with DS (8-62 months of age) and 240 adults with DS (16-71 years of age) during the period from 2013 to 2018 at a research center to examine the association between APOE status (ε4 carrier vs ε4 noncarrier) and attentional abilities. Exposure: APOE status (ε4 carrier vs ε4 noncarrier). Main Outcomes and Measures: For the children, attentional ability was assessed using an eye-tracking paradigm, the gap-overlap task; the size of the gap effect was the primary outcome. For the adults, attentional ability was assessed using the CANTAB simple reaction time task; the standard deviation of response time latencies was the primary outcome. Cross-sectional developmental trajectories were constructed linking attentional ability with age in ε4 carriers and ε4 noncarriers for children and adults separately. Results: The child sample comprised 23 ε4 carriers and 57 ε4 noncarriers. The adult sample comprised 61 ε4 carriers and 179 ε4 noncarriers. For the children, a significant difference between trajectory intercepts (ηp2 = 0.14) indicated that ε4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ε4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]). There was an interaction between APOE status and age (ηp2 = 0.10); while the gap effect decreased with age for ε4 noncarriers (B = -4.58 [95% CI, -6.67 to -2.48]), reflecting the development of the attention system, there was no change across age in ε4 carriers (B = 0.77 [95% CI, -1.57 to 3.12]). For the adults, there was no main effect of ε4 carrier status, but there was an interaction between APOE status and age (B = 0.02 [95% CI, 0.004-0.07]), so that ε4 carriers had poorer attentional ability than ε4 noncarriers at older ages. Conclusions and Relevance: APOE ε4 is associated with an attentional advantage early in development and a disadvantage later in life for individuals with DS, similar to the pattern reported in typical development. Understanding the differential role of APOE across the life span is an important step toward future interventions

Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome

Introduction: Adults with Down syndrome (DS) are at ultra-high risk of developing Alzheimer's disease (AD), characterized by poor episodic memory and semantic fluency in the preclinical phase in the general population. We explored semantic fluency performance in DS and its relationship to age, AD, and blood biomarkers. Methods: A total of 302 adults with DS at baseline and 87 at follow-up from the London Down Syndrome Consortium cohort completed neuropsychological assessments. Blood biomarkers were measured with the single molecule array technique in a subset of 94 participants. Results: Poorer verbal fluency performance was observed as age increases. Number of correct words declined in those with AD compared to those without over 2 years and was negatively correlated with neurofilament light (r = –0.37, P =.001) and glial fibrillary acidic protein (r = –0.31, P =.012). Discussion: Semantic fluency may be useful as an early indicator of cognitive decline and provide additional information on AD-related change, showing associations with biomarkers in DS

Integrated weed management of medicinal plants in India

The present as well as future need is to diversify the agro-ecosystem and to minimize or overcome the bad effects of global warming and climate change. Medicinal plants survive very well in the current scheme of crop diversification in various types of agro-climatic conditions of India. Agronomists are posed with challenge of scientifically fitting most suitable medicinal plants in different ago-climatic regions. Among the losses caused by different pests in the agriculture, the weeds account for about 45% and it may be more or less equal in the case of medicinal plants. Integrated weed management increases the factor productivity, income of the farmer, quality of produce and is eco-friendly in nature. By taking examples of two important medicinal plants viz. Satawar (Asparagus racemosus Willd.) and Kalmegh (Andrographis paniculata Nees.), the present review discusses the different methods of weed management and how they may be integrated to develop new paradigm as an integrated weed management

Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease

OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10−6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production

The Tumor Suppressor Gene, RASSF1A, Is Essential for Protection against Inflammation -Induced Injury

10.1371/journal.pone.0075483PLoS ONE810-POLN

Myogenic progenitors contribute to open but not closed fracture repair

<p>Abstract</p> <p>Background</p> <p>Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.</p> <p>Methods</p> <p>We employed a <it>MyoD</it>-Cre⁺:Z/AP⁺conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a <it>human alkaline phosphatase (hAP) </it>reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.</p> <p>Results</p> <p>In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP⁺cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP⁺cells detected in the open fracture callus. At early stages of repair, many hAP⁺cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP⁺cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP⁺staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.</p> <p>Conclusions</p> <p>These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.</p> <p>Please see related article: <url>http://www.biomedcentral.com/1741-7015/9/136</url></p

Body mass estimation from footprint size in hominins.

Although many studies relating stature to foot length have been carried out, the relationship between foot size and body mass remains poorly understood. Here we investigate this relationship in 193 adult and 50 juvenile habitually unshod/minimally shod individuals from five different populations-Machiguenga, Daasanach, Pumé, Hadzabe, and Samoans-varying greatly in body size and shape. Body mass is highly correlated with foot size, and can be predicted from foot area (maximum length × breadth) in the combined sample with an average error of about 10%. However, comparisons among populations indicate that body shape, as represented by the body mass index (BMI), has a significant effect on foot size proportions, with higher BMI samples exhibiting relatively smaller feet. Thus, we also derive equations for estimating body mass from both foot size and BMI, with BMI in footprint samples taken as an average value for a taxon or population, estimated independently from skeletal remains. Techniques are also developed for estimating body mass in juveniles, who have relatively larger feet than adults, and for converting between foot and footprint size. Sample applications are given for five Pliocene through Holocene hominin footprint samples from Laetoli (Australopithecus afarensis), Ileret (probable Homo erectus), Happisburgh (possible Homo antecessor), Le Rozel (archaic Homo sapiens), and Barcin Höyük (H. sapiens). Body mass estimates for Homo footprint samples appear reasonable when compared to skeletal estimates for related samples. However, estimates for the Laetoli footprint sample using the new formulae appear to be too high when compared to skeletal estimates for A. afarensis. Based on the proportions of A.L. 288-1, this is apparently a result of relatively large feet in this taxon. A different method using a ratio between body mass and foot area in A.L. 288-1 provides estimates more concordant with skeletal estimates and should be used for A. afarensis

Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas

<p>Abstract</p> <p>Background</p> <p>Loss of heterozygosity of chromosome 10q26 has been shown to be associated with the aggressiveness of astrocytic tumors (or astrocytomas), but the responsible gene(s) residing in this region has not been fully identified. The <it>BCCIP </it>gene is located at chromosome 10q26. It encodes a BRCA2 and CDKN1A (p21) interacting protein. Previous studies have shown that down-regulation of BCCIP impairs recombinational DNA repair, G1/S cell cycle checkpoint, p53 trans-activation activity, cytokinesis, and chromosome stability, suggesting a potential role of <it>BCCIP </it>in cancer etiology. In this study, we investigated whether <it>BCCIP </it>is altered in astrocytomas.</p> <p>Methods</p> <p>Genomic DNA from 45 cases of grade IV astrocytic tumor (glioblastoma) tissues and 12 cases of normal tissues were analyzed by quantitative PCR. The BCCIP protein expression in 96 cases of grade II–IV astrocytic tumors was detected by immunohistochemistry (IHC). IHC staining of glial fibrillary acid protein (GFAP), a marker for astrocytic cells, was used to identify cells of the astrocytic lineage.</p> <p>Results</p> <p>We found that BCCIP protein is expressed in normal cells with positive staining of GFAP. However, BCCIP protein expression was not detectable in ~45% of all astrocytic tumors, and in > 60% in the grade IV glioblastoma. About 45% glioblastoma have significant (p < 0.01) reduction of <it>BCCIP </it>gene copy number when compared to normal DNA. Furthermore, the frequency of lacking BCCIP expression is associated with the aggressiveness of astrocytic tumors.</p> <p>Conclusion</p> <p>Our data implicate a role of BCCIP in astrocytic tumorigenesis, and lack of <it>BCCIP </it>may be used as a marker for astrocytomas.</p