Menstrual cycle and hormonal contraceptive symptom severity and frequency in athletic females

The purpose of this study was to determine symptom severity and frequency in female exercisers and athletes from a diverse range of sports who have a menstrual cycle (MC) or use hormonal contraceptives (HCs). An additional aim was to explore the perceived impact of MC/HC use upon exercise and sport performance. In total, 604 self-identifying female athletes and exercisers (M = 29.4 years, SD = 9.0) from 85 sports/activities completed a survey which included: sport/exercise participation, bleeding characteristics, HC use, symptom severity/frequency, symptom management strategies, menstrual product use, and perceived impact of MC/HC use on exercise performance. The data were subject to mixed-methods analysis. Over one third (n = 225; 37.25%) of participants reported current HC use. Ninety-five percent (95.36%) of participants experienced symptoms related to MC or HC use. Physiological, psychological, and affective symptoms were all among the most prevalent. The most frequently noted severe and very severe symptoms for all participants, MC and HC users, were abdominal cramps (36.92%, 39.32%, and 32.89%, respectively), mood changes (26.16%, 25.07%, and 28.00%, respectively), and tiredness (25.33%, 25.59%, and 24.89%, respectively). Symptom impact was self-managed through medical and/or other (cognitive/behavioral) strategies. Qualitative content analysis of the data produced four overarching themes: (a) the impact of symptoms, (b) menstrual stigma and taboos, (c) protective factors, and (d) coping strategies. In conclusion, menstruation is a multifaceted, unique experience that impacts upon sport/exercise performance. Practitioners should consider athletes’ distinct needs, including the frequency of occurrence and severity of their symptomatic experiences, when facilitating menstruation-supportive training, avoiding a “one-size fits-all” approach

DVT Surveillance Program in the ICU: Analysis of Cost-Effectiveness

Background Venous Thrombo-embolism (VTE – Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) – in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis. Methods All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period – SP). The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP). All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs – diagnostic, therapeutic and surveillance – for both periods were recorded and the incremental cost for each Quality Adjusted Life Year (QALY) gained was calculated. Results 4234 patients were eligible (PSP – 1422 and SP – 2812). Rate of DVT in SP (2.8%) was significantly higher than in PSP (1.3%) – p Conclusions Surveillance of traumatized ICU patients increases DVT detection and reduces PE incidence. Costs in terms of QALY gained compares favorably with other interventions accepted by society

Interleukin-1α Activity in Necrotic Endothelial Cells Is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2: IMPLICATIONS FOR ALLOGRAFT REJECTION.

Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection.This study was supported by British Heart Foundation Grants FS/09/005/26845, FS/13/3/30038 and FS/11/77/29327 (MCHC) & RG/13/14/30314 (MRB); the BHF Cambridge CRE; and the NIHR Cambridge BRC.This is the final version of the article. It first appeared from ASBMB via http://dx.doi.org/10.1074/jbc.M115.66791

Winning and losing: differences in reward and punishment sensitivity between smokers and nonsmokers

Background: Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processing brain regions, while others show decreased activation or no difference in activation between smokers and nonsmokers. Aims: The goal of the current study is to see if smokers process the evaluation and delivery of equally salient real world rewards similarly or differently than nonsmokers. Methods: The current study employed functional magnetic resonance imaging (fMRI) to examine brain responses in smokers and nonsmokers during the evaluation and delivery of monetary gains and losses. Results: In comparison to nonsmokers, smokers showed increased activation in the ventromedial prefrontal cortex to the evaluation of anticipated monetary losses and the brain response. Moreover, smokers compared to nonsmokers showed decreased activation in the inferior frontal gyrus to the delivery of expected monetary gains. Brain activations to both the evaluation of anticipated monetary losses and the delivery of expected monetary gains correlated with increased self-reported smoking craving to relieve negative withdrawal symptoms and craving related to positive aspects of smoking, respectively. Discussion: Together these results indicate that smokers are hyperresponsive to the evaluation of anticipated punishment and hyporesponsive to the delivery of expected rewards. Although further research is needed, this hypersensitivity to punishments coupled with increased craving may negatively impact quit attempts as smokers anticipate the negative withdrawal symptoms associated with quitting

The distinct features of microbial 'dysbiosis' of Crohn's disease do not occur to the same extent in their unaffected, genetically linked kindred

Background/Aims: Studying the gut microbiota in unaffected relatives of people with Crohn’s disease (CD) may advance our understanding of the role of bacteria in disease aetiology. Methods: Faecal microbiota composition (16S rRNA gene sequencing), genetic functional capacity (shotgun metagenomics) and faecal short chain fatty acids (SCFA) were compared in unaffected adult relatives of CD children (CDR, n = 17) and adult healthy controls, unrelated to CD patients (HUC, n = 14). The microbiota characteristics of 19 CD children were used as a benchmark of CD ‘dysbiosis’. Results: The CDR microbiota was less diverse (p = 0.044) than that of the HUC group. Local contribution of β-diversity analysis showed no difference in community structure between the CDR and HUC groups. Twenty one of 1,243 (1.8%) operational taxonomic units discriminated CDR from HUC. The metagenomic functional capacity (p = 0.207) and SCFA concentration or pattern were similar between CDR and HUC (p>0.05 for all SCFA). None of the KEGG metabolic pathways were different between these two groups. Both of these groups (HUC and CDR) had a higher microbiota α-diversity (CDR, p = 0.026 and HUC, p<0.001) with a community structure (β-diversity) distinct from that of children with CD. Conclusions: While some alterations were observed, a distinct microbial ‘dysbiosis’, characteristic of CD patients, was not observed in their unaffected, genetically linked kindred

Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells

BRAF inhibitors can extend progression-free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. We show that the resistant cells are more sensitive to mitochondrial poisons and to inhibitors of glutaminolysis, suggesting that targeting specific metabolic pathways may offer exciting therapeutic opportunities to treat resistant tumors, or to delay emergence of resistance in the first-line setting

ALMA Multi-line Imaging of the Nearby Starburst Galaxy NGC 253

We present spatially resolved ($\sim$50 pc) imaging of molecular gas species in the central kiloparsec of the nearby starburst galaxy NGC 253, based on observations taken with the Atacama Large Millimeter/submillimeter Array (ALMA). A total of 50 molecular lines are detected over a 13 GHz bandwidth imaged in the 3 mm band. Unambiguous identifications are assigned for 27 lines. Based on the measured high CO/C$^{17}$O isotopic line ratio ($\gtrsim$350), we show that $^{12}$CO(1-0) has moderate optical depths. A comparison of the HCN and HCO$^{+}$ with their $^{13}$C-substituted isotopologues shows that the HCN(1-0) and HCO$^{+}$(1-0) lines have optical depths at least comparable to CO(1-0). H$^{13}$CN/H$^{13}$CO$^{+}$ (and H$^{13}$CN/HN$^{13}$C) line ratios provide tighter constraints on dense gas properties in this starburst. SiO has elevated abundances across the nucleus. HNCO has the most distinctive morphology of all the bright lines, with its global luminosity dominated by the outer parts of the central region. The dramatic variation seen in the HNCO/SiO line ratio suggests that some of the chemical signatures of shocked gas are being erased in the presence of dominating central radiation fields (traced by C$_{2}$H and CN). High density molecular gas tracers (including HCN, HCO$^+$, and CN) are detected at the base of the molecular outflow. We also detect hydrogen $\beta$ recombination lines that, like their $\alpha$ counterparts, show compact, centrally peaked morphologies, distinct from the molecular gas tracers. A number of sulfur based species are mapped (CS, SO, NS, C$_{2}$S, H$_{2}$CS and CH$_{3}$SH) and have morphologies similar to SiO.Comment: 20 pages, 10 figures, accepted to the Astrophysical Journa

Collimation and asymmetry of the hot blast wave from the recurrent nova V745 Scorpii

The recurrent symbiotic nova V745 Sco exploded on 2014 February 6 and was observed on February 22 and 23 by the Chandra X-ray Observatory Transmission Grating Spectrometers. By that time the supersoft source phase had already ended and Chandra spectra are consistent with emission from a hot, shock-heated circumstellar medium with temperatures exceeding 10^7K. X-ray line profiles are more sharply peaked than expected for a spherically-symmetric blast wave, with a full width at zero intensity of approximately 2400 km/s, a full width at half maximum of 1200 +/- 30 km/s and an average net blueshift of 165 +/- 10 km/s. The red wings of lines are increasingly absorbed toward longer wavelengths by material within the remnant. We conclude that the blast wave was sculpted by an aspherical circumstellar medium in which an equatorial density enhancement plays a role, as in earlier symbiotic nova explosions. Expansion of the dominant X-ray emitting material is aligned close to the plane of the sky and most consistent with an orbit seen close to face-on. Comparison of an analytical blast wave model with the X-ray spectra, Swift observations and near-infrared line widths indicates the explosion energy was approximately 10^43 erg, and confirms an ejected mass of approximately 10^-7 Msun. The total mass lost is an order of magnitude lower than the accreted mass required to have initiated the explosion, indicating the white dwarf is gaining mass and is a supernova Type 1a progenitor candidate.Comment: To appear in the Astrophysical Journa

The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.

The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage