Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity

We examined the association between non-steroidal anti-inflammatory drug (NSAID) use and ovarian cancer by potential effect modifiers, parity and oral contraceptive use, in a population-based case–control study conducted in Wisconsin and Massachusetts. Women reported prior use of NSAIDs and information on risk factors in a telephone interview. A total of 487 invasive ovarian cancer cases and 2653 control women aged 20–74 years were included in the analysis. After adjustment for age, state of residence and other covariates, ever use of NSAIDs was inversely associated with ovarian cancer in never users of oral contraceptives (odds ratio (OR)=0.58, 95% confidence interval (CI) 0.42–0.80) but not for ever users (OR=0.98, 95% CI 0.71–1.35) (P-interaction=0.03). A reduced risk with NSAID use was also noted in nulliparous women (OR=0.47, 95% CI 0.27–0.82) but not among parous women (OR=0.81, 95% CI 0.64–1.04) (P-interaction=0.05). These results suggest that use of NSAIDs were beneficial to women at greatest risk for ovarian cancer

Deconstruction of the (Paleo)Polyploid Grapevine Genome Based on the Analysis of Transposition Events Involving NBS Resistance Genes

Plants have followed a reticulate type of evolution and taxa have frequently merged via allopolyploidization. A polyploid structure of sequenced genomes has often been proposed, but the chromosomes belonging to putative component genomes are difficult to identify. The 19 grapevine chromosomes are evolutionary stable structures: their homologous triplets have strongly conserved gene order, interrupted by rare translocations. The aim of this study is to examine how the grapevine nucleotide-binding site (NBS)-encoding resistance (NBS-R) genes have evolved in the genomic context and to understand mechanisms for the genome evolution. We show that, in grapevine, i) helitrons have significantly contributed to transposition of NBS-R genes, and ii) NBS-R gene cluster similarity indicates the existence of two groups of chromosomes (named as Va and Vc) that may have evolved independently. Chromosome triplets consist of two Va and one Vc chromosomes, as expected from the tetraploid and diploid conditions of the two component genomes. The hexaploid state could have been derived from either allopolyploidy or the separation of the Va and Vc component genomes in the same nucleus before fusion, as known for Rosaceae species. Time estimation indicates that grapevine component genomes may have fused about 60 mya, having had at least 40–60 mya to evolve independently. Chromosome number variation in the Vitaceae and related families, and the gap between the time of eudicot radiation and the age of Vitaceae fossils, are accounted for by our hypothesis

Diseases of the salivary glands in infants and adolescents

<p>Abstract</p> <p>Background</p> <p>Diseases of the salivary glands are rare in infants and children (with the exception of diseases such as parotitis epidemica and cytomegaly) and the therapeutic regimen differs from that in adults. It is therefore all the more important to gain exact and extensive insight into general and special aspects of pathological changes of the salivary glands in these age groups. Etiology and pathogenesis of these entities is still not yet fully known for the age group in question so that general rules for treatment, based on clinical experience, cannot be given, particularly in view of the small number of cases of the different diseases. Swellings of the salivary glands may be caused by acute and chronic inflammatory processes, by autoimmune diseases, by duct translocation due to sialolithiasis, and by tumors of varying dignity. Clinical examination and diagnosis has also to differentiate between salivary gland cysts and inflammation or tumors.</p> <p>Conclusion</p> <p>Salivary gland diseases are rare in childhood and adolescence. Their pattern of incidence differs very much from that of adults. Acute and chronic sialadenitis not responding to conservative treatment requires an appropriate surgical approach. The rareness of salivary gland tumors is particularly true for the malignant parotid tumors which are more frequent in juvenile patients, a fact that has to be considered in diagnosis and therapy.</p

Impact of Circulating Cholesterol Levels on Growth and Intratumoral Androgen Concentration of Prostate Tumors

Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol. Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025) Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis. Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR

Association of predicted 10 years cardiovascular mortality risk with duration of HIV infection and antiretroviral therapy among HIV-infected individuals in Durban, South Africa

Background: South Africa has the largest population of human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefits of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profile. Methods: We extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥ 30 years. We defined metabolic syndrome (MetS) subcomponents using the International Diabetes Federation definition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into five levels, with the thresholds ranging from very low-risk ( 30%). Results: Among the 384 patients, with a mean (± standard deviation) age of 42.90 ± 8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a definitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44-60) of the patients were stratified to very low risk ( 30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82 ± 6.27 among very high risk and 37.52 ± 4.50; p < 0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p = 0.002) and ART (p = 0.007) were significantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds. Conclusions: Approximately 1 in 10 HIV-infected patients is at very high risk of predicted 10-year CVD mortality in our study population. Like uninfected individuals, our study found increased age as a major predictor of 10-year mortality risk and high prevalence of metabolic syndrome. Additional CVD mortality risk due to the duration of HIV infection and ART was seen in our population, further studies in larger and more representative study samples are encouraged. It recommends an urgent need for early planning, prevention and management of metabolic risk factors in HIV populations, at the point of ART initiation

Global Assessment of Functioning (GAF): properties and frontier of current knowledge

ABSTRACT: BACKGROUND: Global Assessment of Functioning (GAF) is well known internationally and widely used for scoring the severity of illness in psychiatry. Problems with GAF show a need for its further development (for example validity and reliability problems). The aim of the present study was to identify gaps in current knowledge about properties of GAF that are of interest for further development. Properties of GAF are defined as characteristic traits or attributes that serve to define GAF (or may have a role to define a future updated GAF). METHODS: A thorough literature search was conducted. RESULTS: A number of gaps in knowledge about the properties of GAF were identified: for example, the current GAF has a continuous scale, but is a continuous or categorical scale better? Scoring is not performed by setting a mark directly on a visual scale, but could this improve scoring? Would new anchor points, including key words and examples, improve GAF (anchor points for symptoms, functioning, positive mental health, prognosis, improvement of generic properties, exclusion criteria for scoring in 10-point intervals, and anchor points at the endpoints of the scale)? Is a change in the number of anchor points and their distribution over the total scale important? Could better instructions for scoring within 10-point intervals improve scoring? Internationally, both single and dual scales for GAF are used, but what is the advantage of having separate symptom and functioning scales? Symptom (GAF-S) and functioning (GAF-F) scales should score different dimensions and still be correlated, but what is the best combination of definitions for GAF-S and GAF-F? For GAF with more than two scales there is limited empirical testing, but what is gained or lost by using more than two scales? CONCLUSIONS: In the history of GAF, its basic properties have undergone limited changes. Problems with GAF may, in part, be due to lack of a research programme testing the effects of different changes in basic properties. Given the widespread use, research-based development of GAF has not been especially strong. Further research could improve GAF

Dense sampling of bird diversity increases power of comparative genomics (vol 587, pg 252, 2020)

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Inclusive and differential measurements of the t(t)over-bar charge asymmetry in pp collisions at root s=8 TeV

The charge asymmetry is measured in proton–proton collisions at a centre-of-mass energy of . The data, collected with the CMS experiment at the LHC, correspond to an integrated luminosity of 19.7 fb−1. Selected events contain an electron or a muon and four or more jets, where at least one jet is identified as originating from b-quark hadronization. The inclusive charge asymmetry is found to be . In addition, differential charge asymmetries as a function of rapidity, transverse momentum, and invariant mass of the system are studied. For the first time at the LHC, the measurements are also performed in a reduced fiducial phase space of top quark pair production, with an integrated result of . All measurements are consistent within two standard deviations with zero asymmetry as well as with the predictions of the standard model

Erratum to: Comparison of the Z/γ* + jets to γ + jets cross sections in pp collisions at √s = 8

Erratum to: JHEP10(2015)128. ArXiv ePrint: 1505.06520. The online version of the original article can be found at http://dx.doi.org/10.1007/JHEP10(2015)128