One year symptom severity and health-related quality of life changes among Black African patients undergoing uterine fibroid embolisation.

BACKGROUND: The main aim in the treatment of symptomatic fibroids by various modalities including uterine fibroid embolisation (UFE) is to alleviate symptoms and ultimately improve the quality of life. The efficacy of this modality of treatment in Black African women with significant fibroid burden and large uterine volumes is not clear. The main objective of the study was to examine potential changes in symptom severity among Black African patients 1 year following UFE for symptomatic uterine fibroids in a resource-constrained setting, rated using a validated questionnaire (UFS-QOL). Secondary outcomes examined were changes in quality of life and potential associations with age, parity, uterine volume and fibroid number prior to UFE. Additional interventions after UFE were also recorded. METHODS: A prospective before and after study of Black African patients undergoing UFE was undertaken. Participants underwent pelvic MR imaging prior to UFE and completed the UFS-QOL, a validated condition-specific questionnaire at baseline and at 1 year. Ninety five participants were recruited and data from 80 completing 1 year of follow up were available for analysis of changes in the symptom severity scores. RESULTS: The mean reduction in symptom severity score was 29.6 [95% CI 23.6 to 35.6, P < 0.001] and the mean improvement in HRQOL score was 35.7 [95% CI 28.4 to 42.9, P < 0.001]. A greater number of fibroids identified prior to UFE was associated with a more substantial improvement in symptom severity score (rs = 0.28, n = 80, P = 0.013) and participants of higher parity reported a greater improvement in HRQOL score (r = 0.336, P = 0.002). Major and minor surgical interventions were needed in 5 (6.3%) and 10 (12.5%) participants respectively. CONCLUSIONS: UFE is associated with clinically useful and statistically significant symptom relief in Black African patients. Symptom improvement following UFE is not compromised by a large fibroid burden and the rate of subsequent intervention is within an acceptable range. UFE is a safe alternative and efforts are needed to widen access to this non-surgical treatment modality

Global metabolomic profiling of uterine leiomyomas

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.Peer reviewe

GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens

Individual tree and stand-level carbon and nutrient contents across one rotation of loblolly pine plantations on a reclaimed surface mine

While reclaimed loblolly pine (Pinus taeda L.) plantations in east Texas, USA have demonstrated similar aboveground productivity levels relative to unmined forests, there is interest in assessing carbon (C) and nutrients in aboveground components of reclaimed trees. Numerous studies have previously documented aboveground biomass, C, and nutrient contents in loblolly pine plantations; however, similar data have not been collected on mined lands. We investigated C, N, P, K, Ca, and Mg aboveground contents for first-rotation loblolly pine growing on reclaimed mined lands in the Gulf Coastal Plain over a 32-year chronosequence and correlated elemental rates to stand age, stem growth, and similar data for unmined lands. At the individual tree level, we evaluated elemental contents in aboveground biomass components using tree size, age, and site index as predictor variables. At the stand-level, we then scaled individual tree C and nutrients and fit a model to determine the sensitivity of aboveground elemental contents to stand age and site index. Our data suggest that aboveground C and nutrients in loblolly pine on mined lands exceed or follow similar trends to data for unmined pine plantations derived from the literature. Diameter and height were the best predictors of individual tree stem C and nutrient contents (R ≥ 0.9473 and 0.9280, respectively) followed by stand age (R ≥ 0.8660). Foliage produced weaker relationships across all predictor variables compared to stem, though still significant (P ≤ 0.05). The model for estimating stand-level C and nutrients using stand age provided a good fit, indicating that contents aggrade over time predictably. Results of this study show successful modelling of reclaimed loblolly pine aboveground C and nutrients, and suggest elemental cycling is comparable to unmined lands, thus providing applicability of our model to related systems

New Information on the Cranial Anatomy of Acrocanthosaurus atokensis and Its Implications for the Phylogeny of Allosauroidea (Dinosauria: Theropoda)

Allosauroidea has a contentious taxonomic and systematic history. Within this group of theropod dinosaurs, considerable debate has surrounded the phylogenetic position of the large-bodied allosauroid Acrocanthosaurus atokensis from the Lower Cretaceous Antlers Formation of North America. Several prior analyses recover Acrocanthosaurus atokensis as sister taxon to the smaller-bodied Allosaurus fragilis known from North America and Europe, and others nest Acrocanthosaurus atokensis within Carcharodontosauridae, a large-bodied group of allosauroids that attained a cosmopolitan distribution during the Early Cretaceous.Re-evaluation of a well-preserved skull of Acrocanthosaurus atokensis (NCSM 14345) provides new information regarding the palatal complex and inner surfaces of the skull and mandible. Previously inaccessible internal views and articular surfaces of nearly every element of the skull are described. Twenty-four new morphological characters are identified as variable in Allosauroidea, combined with 153 previously published characters, and evaluated for eighteen terminal taxa. Systematic analysis of this dataset recovers a single most parsimonious topology placing Acrocanthosaurus atokensis as a member of Allosauroidea, in agreement with several recent analyses that nest the taxon well within Carcharodontosauridae.A revised diagnosis of Acrocanthosaurus atokensis finds that the species is distinguished by four primary characters, including: presence of a knob on the lateral surangular shelf; enlarged posterior surangular foramen; supraoccipital protruding as a double-boss posterior to the nuchal crest; and pneumatic recess within the medial surface of the quadrate. Furthermore, the recovered phylogeny more closely agrees with the stratigraphic record than hypotheses that place Acrocanthosaurus atokensis as more closely related to Allosaurus fragilis. Fitch optimization of body size is also more consistent with the placement of Acrocanthosaurus atokensis within a clade of larger carcharodontosaurid taxa than with smaller-bodied taxa near the base of Allosauroidea. This placement of Acrocanthosaurus atokensis supports previous hypotheses of a global carcharodontosaurid radiation during the Early Cretaceous

Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study.

PURPOSE: CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain. METHODS: The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken. RESULTS: There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and ≥ 40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m(2) of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed. CONCLUSION: The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate