Health-related quality of life and anemia in hospitalized patients with heart failure

AbstractBackgroundAnemia is a serious and highly prevalent co-morbidity in chronic heart failure (HF) patients. Its influence on health-related quality of life (HR-QoL) has rarely been studied, and no data is available regarding the role it plays in hospitalized HF patients.MethodsBaseline data from the COACH study (Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure) were used. HR-QoL was assessed by means of generic and disease-specific questionnaires. Analyses were performed using ANOVA and ANCOVA, with covariates of age, gender, eGFR, diabetes, and NYHA class.ResultsIn total, 1013 hospitalized patients with a mean age of 71 (SD 11) years were included; 70% of these patients had no anemia (n=712), 14% had mild anemia (n=141), and 16% had moderate-to-severe anemia (n=160). Independent associations were found between anemia and physical functioning (p=0.019), anemia and role limitations due to physical functioning (p=0.002), anemia and general health (p=0.024), and anemia and global well-being (p=0.003).ConclusionIn addition to the burden of HF itself, anemia is an important factor which influences HR-QoL in hospitalized HF patients, and one that is most pronounced in the domain related to physical functioning and general health

Incidence and Severity of Sexual Harassment, and its Impact on Mental Health in a Cohort of International Humanitarian Field-Workers

To date, there have been no cohort studies of sexual harassment incidence and its relation to mental health within humanitarian field-workers. Research among numerous occupations suggests an association between workplace sexual harassment and several health complaints. This study examined the incidence and severity of sexual harassment and its association with changes in mental health in a cohort of international humanitarian aid field-workers (iHAWs). Four hundred and seventy-eight iHAWs filled in questionnaires about sexual harassment, depression, anxiety, and Post-Traumatic Stress Disorder (PTSD) as part of a larger study on health and well-being. Six percent of male and 18% of female iHAWs reported experiencing sexual harassment during their latest field assignment, with most reporting low levels of nonphysical forms of sexual harassment. Sexual harassment was predictive of negative changes in both depression and anxiety symptom severity between before and after an assignment for females; for males, it predicted negative changes in PTSD symptom severity. Sexual harassment did not predict utilization of mental healthcare services within 2 months after the end of assignment. The current findings are the first figures derived from a representative sample of iHAWs on the incidence of sexual harassment during a field assignment and show sexual harassment to be a relatively common and present issue. The findings are mostly in line with the extant literature and underscore the importance of attending to the issue of sexual harassment in the humanitarian sector

Health trajectories of international humanitarian aid workers: growth mixture modelling findings from a prospective cohort study

Background  Most staff stay healthy during humanitarian work, although some worsen. Mean scores on health indicators may be masking individual participants struggling with health issues. Aims To investigate different field assignment-related health trajectories among international humanitarian aid workers (iHAWs) and explore the mechanisms used to stay healthy.  Method  Growth mixture modelling analyses for five health indicators using pre-/post-assignment and follow-up data.  Results  Among 609 iHAWs three trajectories (profiles) were found for emotional exhaustion, work engagement, anxiety and depression. For post-traumatic stress disorder (PTSD) symptoms, four trajectories were identified. The 'healthy/normative' trajectory had the largest sample size for all health indicators (73-86%). A stable (moderate) 'ill health' trajectory was identified for all health indicators (7-17%), except anxiety. An 'improving' trajectory was found for PTSD and anxiety symptoms (5-14%). A minority of staff (4-15%) worsened on all health indicators. Deterioration continued for PTSD, depressive symptoms and work engagement 2 months post-assignment. A strong sense of coherence was associated with higher odds of belonging to the 'healthy' trajectory. Female biological sex was associated with higher odds of belonging to the 'worsening' depression and anxiety trajectories. Extended duration of field assignment was related to higher odds of belonging to the 'worsening' depressive symptoms trajectory.  Conclusions  Most iHAWs stayed healthy during their assignment; a stable 'ill health' trajectory was identified for most health indicators. Sense of coherence is an important mechanism for understanding the health of all iHAWs in the different health trajectories, including the 'healthy' profile. These findings give new possibilities to develop activities to prevent worsening health and help strengthen iHAWs' ability to remain healthy under stress

Companion Animals as a Source of Viruses for Human Beings and Food Production Animals

Companion animals comprise a wide variety of species, including dogs, cats, horses, ferrets, guinea pigs, reptiles, birds and ornamental fish, as well as food production animal species, such as domestic pigs, kept as companion animals. Despite their prominent place in human society, little is known about the role of companion animals as sources of viruses for people and food production animals. Therefore, we reviewed the literature for accounts of infections of companion animals by zoonotic viruses and viruses of food production animals, and prioritized these viruses in terms of human health and economic importance. In total, 138 virus species reportedly capable of infecting companion animals were of concern for human and food production animal health: 59 of these viruses were infectious for human beings, 135 were infectious for food production mammals and birds, and 22 were infectious for food production fishes. Viruses of highest concern for human health included hantaviruses, Tahyna virus, rabies virus, West Nile virus, tick-borne encephalitis virus, Crimean-Congo haemorrhagic fever virus, Aichi virus, European bat lyssavirus, hepatitis E virus, cowpox virus, G5 rotavirus, influenza A virus and lymphocytic choriomeningitis virus. Viruses of highest concern for food production mammals and birds included bluetongue virus, African swine fever virus, foot-and-mouth disease virus, lumpy skin disease virus, Rift Valley fever virus, porcine circovirus, classical swine fever virus, equine herpesvirus 9, peste des petits ruminants virus and equine infectious anaemia virus. Viruses of highest concern for food production fishes included cyprinid herpesvirus 3 (koi herpesvirus), viral haemorrhagic septicaemia virus and infectious pancreatic necrosis virus. Of particular concern as sources of zoonotic or food production animal viruses were domestic carnivores, rodents and food production animals kept as companion animals. The current list of viruses provides an objective basis for more in-depth analysis of the risk of companion animals as sources of viruses for human and food production animal health

Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status

Chondrosarcomas are chemo- and radiotherapy resistant and frequently harbor mutationsin isocitrate dehydrogenase (IDH1 or IDH2), causing increased levels of D-2-hydroxyglutarate(D-2-HG). DNA repair defects and synthetic lethality with poly(ADP-ribose) polymerase (PARP)inhibition occur in IDH mutant glioma and leukemia models. Here we evaluated DNA repairand PARP inhibition, alone or combined with chemo- or radiotherapy, in chondrosarcoma celllines with or without endogenous IDH mutations. Chondrosarcoma cell lines treated with thePARP inhibitor talazoparib were examined for dose–response relationships, as well as underlyingcell death mechanisms and DNA repair functionality. Talazoparib was combined with chemo- orradiotherapy to evaluate potential synergy. Cell lines treated long termwith an inhibitor normalizingD-2-HG levels were investigated for synthetic lethality with talazoparib. We report that talazoparibsensitivity was variable and irrespective of IDH mutation status. All cell lines expressed AtaxiaTelangiectasia Mutated (ATM), but a subset was impaired in poly(ADP-ribosyl)ation (PARylation)capacity, homologous recombination, andO-6-methylguanine-DNAmethyltransferase (MGMT) expression.Talazoparib synergized with temozolomide or radiation, independent of IDH1 mutant inhibition.This study suggests that talazoparib combined with temozolomide or radiation are promisingtherapeutic strategies for chondrosarcoma, irrespective of IDH mutation status. A subset ofchondrosarcomas may be deficient in nonclassical DNA repair pathways, suggesting that PARPinhibitor sensitivity is multifactorial in chondrosarcoma.Toxicolog

Targeting survivin as a potential new treatment for chondrosarcoma of bone

Chondrosarcomas are malignant cartilage-forming bone tumors, which are intrinsically resistant to chemo- and radiotherapy, leaving surgical removal as the only curative treatment option. Therefore, our aim was to identify genes involved in chondrosarcoma cell survival that could serve as a target for therapy. siRNA screening for 51 apoptosis-related genes in JJ012 chondrosarcoma cells identified BIRC5, encoding survivin, as essential for chondrosarcoma survival. Using immunohistochemistry, nuclear as well as cytoplasmic survivin expression was analyzed in 207 chondrosarcomas of different subtypes. Nuclear survivin has been implicated in cell-cycle regulation while cytoplasmic localization is important for its anti-apoptotic function. RT-PCR was performed to determine expression of the most common survivin isoforms. Sensitivity to YM155, a survivin inhibitor currently in phase I/II clinical trial for other tumors, was examined in 10 chondrosarcoma cell lines using viability assay, apoptosis assay and cell-cycle analysis. Survivin expression was found in all chondrosarcoma patient samples. Higher expression of nuclear and cytoplasmic survivin was observed with increasing histological grade in central chondrosarcomas. Inhibition of survivin using YM155 showed that especially TP53 mutant cell lines were sensitive, but no caspase 3/7 or PARP cleavage was observed. Rather, YM155 treatment resulted in a block in S phase in two out of three chondrosarcoma cell lines, indicating that survivin is more involved in cell-cycle regulation than in apoptosis. Thus, survivin is important for chondrosarcoma survival and chondrosarcoma patients might benefit from survivin inhibition using YM155, for which TP53 mutational status can serve as a predictive biomarker.Toxicolog

A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell survival

Chondrosarcomas are malignant cartilage tumors that are relatively resistant towards conventional therapeuticapproaches. Kinase inhibitors have been investigated and shown successful for several different cancer types. Inthis study we aimed at identifying kinase inhibitors that inhibit the survival of chondrosarcoma cells and therebyserve as new potential therapeutic strategies to treat chondrosarcoma patients.An siRNA screen targeting 779 different kinases was conducted in JJ012 chondrosarcoma cells in parallelwith a compound screen consisting of 273 kinase inhibitors in JJ012, SW1353 and CH2879 chondrosarcoma celllines. AURKA, CHK1 and PLK1 were identified as most promising targets and validated further in a morecomprehensive panel of chondrosarcoma cell lines. Dose response curves were performed using tyrosine kinaseinhibitors: MK-5108 (AURKA), LY2603618 (CHK1) and Volasertib (PLK1) using viability assays and cell cycleanalysis. Apoptosis was measured at 24 h after treatment using a caspase 3/7 assay. Finally, chondrosarcomapatient samples (N = =34) were used to examine the correlation between AURKA, CHK1 and PLK1 RNAexpression and documented patient survival.Dose dependent decreases in viability were observed in chondrosarcoma cell lines after treatment with MK-5108, LY2603618 and volasertib, with cell lines showing highest sensitivity to PLK1 inhibition. In additionincreased sensitivity to conventional chemotherapy was observed after CHK1 inhibition in a subset of the celllines. Interestingly, whereas AURKA and CHK1 were both expressed in chondrosarcoma patient samples, PLK1expression was found to be low compared to normal cartilage. Analysis of patient samples revealed that highCHK1 RNA expression correlated with a worse overall survival.AURKA, CHK1 and PLK1 are identified as important survival genes in chondrosarcoma cell lines. Althoughfurther research is needed to validate these findings, inhibiting CHK1 seems to be the most promising potentialtherapeutic target for patients with chondrosarcoma.Toxicolog

Measurement of the W+W-gamma Cross Section and Direct Limits on Anomalous Quartic Gauge Boson Couplings at LEP

The process e+e- -> W+W-gamma is analysed using the data collected with the L3 detector at LEP at a centre-of-mass energy of 188.6GeV, corresponding to an integrated luminosity of 176.8pb^-1. Based on a sample of 42 selected W+W- candidates containing an isolated hard photon, the W+W-gamma cross section, defined within phase-space cuts, is measured to be: sigma_WWgamma = 290 +/- 80 +/- 16 fb, consistent with the Standard Model expectation. Including the process e+e- -> nu nu gamma gamma, limits are derived on anomalous contributions to the Standard Model quartic vertices W+W- gamma gamma and W+W-Z gamma at 95% CL: -0.043 GeV^-2 < a_0/Lambda^2 < 0.043 GeV^-2 0.08 GeV^-2 < a_c/Lambda^2 < 0.13 GeV^-2 0.41 GeV^-2 < a_n/Lambda^2 < 0.37 GeV^-2

Production of Single W Bosons at \sqrt{s}=189 GeV and Measurement of WWgamma Gauge Couplings

Single W boson production in electron-positron collisions is studied with the L3 detector at LEP. The data sample collected at a centre-of-mass energy of \sqrt{s} = 188.7GeV corresponds to an integrated luminosity of 176.4pb^-1. Events with a single energetic lepton or two acoplanar hadronic jets are selected. Within phase-space cuts, the total cross-section is measured to be 0.53 +/- 0.12 +/- 0.03 pb, consistent with the Standard Model expectation. Including our single W boson results obtained at lower \sqrt{s}, the WWgamma gauge couplings kappa_gamma and lambda_gamma are determined to be kappa_gamma = 0.93 +/- 0.16 +/- 0.09 and lambda_gamma = -0.31 +0.68 -0.19 +/- 0.13

Search for an invisibly decaying Higgs boson in e^+e^- collisions at \sqrt{s} = 183 - 189 GeV

A search for a Higgs boson decaying into invisible particles is performed using the data collected at LEP by the L3 experiment at centre-of-mass energies of 183 GeV and 189 GeV. The integrated luminosities are respectively 55.3 pb^-1 and 176.4 pb^-1. The observed candidates are consistent with the expectations from Standard Model processes. In the hypothesis that the production cross section of this Higgs boson equals the Standard Model one and the branching ratio into invisible particles is 100%, a lower mass limit of 89.2 GeV is set at 95% confidence level