Dairy producer attitudes to pain in cattle in relation to disbudding calves

Pain is an important indicator of poor welfare of livestock. Despite this, pain has largely gone unrecognized in farm animals due to attitudes of producers and veterinarians, although they play a key role in monitoring and managing the perception of animal pain. Producer attitudes toward animal welfare influence livestock management and production. The aim was to quantify dairy producer attitudes to the painfulness of various cattle diseases and disbudding, a painful routine procedure performed on farm to ensure safer handling of cattle. A questionnaire on disbudding-related opinions and practices was sent to 1,000 Finnish dairy producers (response rate: 45%). Attitudes toward disbudding were gauged using a 5-point Likert scale and attitudes to cattle pain scored on an 11-point numerical rating scale. Principal components analysis was used to assess the loadings, which were further tested for differences between producer gender and housing systems with Mann-Whitney U-tests, and between herd milk yield, herd size, and age and work experience of producers with a Kruskal-Wallis test. Four main factors were identified: factor I (“taking disbudding pain seriously”), factor II (“sensitivity to pain caused by cattle diseases”), factor III (“ready to medicate calves myself”), and factor IV (“pro horns”). Female producers took disbudding pain more seriously, were more sensitive to pain caused to cattle by diseases, and were more ready to medicate disbudded calves than male producers. Producers with tie-stalls favored horns over producers with freestalls. Male producers with tie-stalls were sensitive to cattle pain and preferred horns over male producers with freestalls. Female producers with freestalls were more ready to medicate calves, but did not prefer horns more than female producers with tie-stalls. Taking disbudding seriously correlated with sensitivity to pain caused by cattle diseases. Producers with low-milk-yielding herds were less willing to medicate calves and more willing to keep cattle with horns than producers with higher-yielding herds. Older producers were more sensitive to cattle pain than middle-aged and younger producers. No effect was established for taking disbudding pain seriously: the pro-horn factor was associated with work experience, age, and herd size. Women rated pain higher and were more positive toward pain medication for animals than men. Maintaining horns are more important for producers with tie-stalls than for those with freestalls.Peer reviewe

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists

Objectives: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. Methods: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. Results: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. Conclusions: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulu

Characterization of different CTC subpopulations in non-small cell lung cancer

Circulating tumour cells (CTCs) serve as valuable biomarkers. However, EpCAM positive CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. First, EpCAM protein expression was analysed in primary and metastatic lung cancer tissue. In both groups 21% of the samples were EpCAM negative. Second, the CellSearch system identified 15% of patients (n = 48) as CTC positive whereas a multiplex RT-PCR for PIK3CA, AKT2, TWIST, and ALDH1 following EGFR, HER2 and EpCAM based enrichment detected CTCs in 29% of the patients. Interestingly, 86% of CTC positive patients were found to express ALDH1. Only 11% of the patients were CTC-positive by both techniques. CTC positivity was associated with patient disease state when assessed by the multiplex RT-PCR assay (p = 0.015). Patients harbouring tumours with an altered EGFR genotype were more frequently CTC-positive compared to patients with EGFR wildtype tumours. In subsets of patients, CTCs were found to express genes involved in resistance to therapy such as HER3 and MET. In conclusion, using multiple targets for CTC capture and identification increases the sensitivity of CTC detection in NSCLC patients, which can be explained by the presence of different CTC subtypes with distinct molecular features

Prevalence, New Incidence, Course, and Risk Factors of PTSD, Depression, Anxiety, and Panic Disorder during the Covid-19 Pandemic in 11 Countries

We aimed to evaluate the prevalence and incidence of post-traumatic stress disorder (PTSD), depression, anxiety, and panic disorder (PD) among citizens in 11 countries during the Covid-19 pandemic. We explored risks and protective factors most associated with the development of these mental health disorders and their course at 68 days follow up. We acquired 9543 unique responses via an online survey that was disseminated in UK, Belgium, Netherlands, Bulgaria, Czech Republic, Finland, India, Latvia, Poland, Romania, and Sweden. The prevalence and new incidence during the pandemic for at least one disorder was 48.6% and 17.6%, with the new incidence of PTSD, anxiety, depression, and panic disorder being 11.4%, 8.4%, 9.3%, and 3%, respectively. Higher resilience was associated with lower mental health burden for all disorders. Ten to thirteen associated factors explained 79% of the variance in PTSD, 80% in anxiety, 78% in depression, and 89% in PD. To reduce the mental health burden, governments should refrain from implementing many highly restrictive and lasting containment measures. Public health campaigns should focus their effort on alleviating stress and fear, promoting resilience, building public trust in government and medical care, and persuading the population of the measures' effectiveness. Psychosocial services and resources should be allocated to facilitate individual and community-level recovery from the pandemic

Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK ® Lung Panel on the MassARRAY ® System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) &gt; 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK ® and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK ® analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK ®. A decrease in ctDNA levels at 4-6 weeks after treatment initiation detected with UltraSEEK ® correlated with prolonged median PFS (46 vs. 6 weeks; p &lt; 0.05) and OS (145 vs. 30 weeks; p &lt; 0.01). Using plasma-derived ccfDNA, the UltraSEEK ® Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response. </p

Gender perspectives on views and preferences of older people on exercise to prevent falls: a systematic mixed studies review

Background: To offer fall prevention exercise programs that attract older people of both sexes there is a need to understand both womens and mens views and preferences regarding these programs. This paper aims to systematically review the literature to explore any underlying gender perspectives or gender interpretations on older peoples views or preferences regarding uptake and adherence to exercise to prevent falls. Methods: A review of the literature was carried out using a convergent qualitative design based on systematic searches of seven electronic databases (PubMed, CINAHL, Amed, PsycINFO, Scopus, PEDro, and OTseeker). Two investigators identified eligible studies. Each included article was read by at least two authors independently to extract data into tables. Views and preferences reported were coded and summarized in themes of facilitators and barriers using a thematic analysis approach. Results: Nine hundred and nine unique studies were identified. Twenty five studies met the criteria for inclusion. Only five of these contained a gender analysis of mens and womens views on fall prevention exercises. The results suggests that both women and men see women as more receptive to and in more need of fall prevention messages. The synthesis from all 25 studies identified six themes illustrating facilitators and six themes describing barriers for older people either starting or adhering to fall prevention exercise. The facilitators were: support from professionals or family; social interaction; perceived benefits; a supportive exercise context; feelings of commitment; and having fun. Barriers were: practical issues; concerns about exercise; unawareness; reduced health status; lack of support; and lack of interest. Considerably more women than men were included in the studies. Conclusion: Although there is plenty of information on the facilitators and barriers to falls prevention exercise in older people, there is a distinct lack of studies investigating differences or similarities in older womens and mens views regarding fall prevention exercise. In order to ensure that fall prevention exercise is appealing to both sexes and that the inclusion of both men and women are encouraged, more research is needed to find out whether gender differences exists and whether practitioners need to offer a range of opportunities and support strategies to attract both women and men to falls prevention exercise.Funding Agencies|Swedish Research Council [2015-03481]; Strategic Research Programme in Care Sciences, Umea University; Karolinska Institute, Sweden; Umea University</p

Aberrant Expression of Proteins Involved in Signal Transduction and DNA Repair Pathways in Lung Cancer and Their Association with Clinical Parameters

Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues.We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA) assay. The results showed that 18 molecules were significantly different (p<0.05) by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction and lipid metabolism, or function as cell surface/matrix proteins. We also validated RPPA results by Western blot and/or immunohistochemical analyses for some of those molecules. Statistical analyses showed that Ku80 levels were significantly higher in tumors of nonsmokers than in those of smokers. Cyclin B1 levels were significantly overexpressed in poorly differentiated tumors while Cox2 levels were significantly overexpressed in neuroendocrinal tumors. A high level of Stat5 is associated with favorable survival outcome for patients treated with surgery.Our results revealed that some molecules involved in DNA damage/repair, signal transductions, lipid metabolism, and cell proliferation were drastically aberrant in lung cancer tissues, and Stat5 may serve a molecular marker for prognosis of lung cancers