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

Fitness and health benefits of team handball training for young untrained women - A cross-disciplinary RCT on physiological adaptations and motivational aspects

Purpose: The present study evaluated the effects of regular participation in small-sided team handball training on body composition, osteogenic response, physical performance, and cardiovascular risk factors, as well as well-being and motivation, in young untrained women. Methods: Twenty-eight untrained 20- to 30-year-old women were randomized to a handball training group (HG; n = 14, height 170 ± 5 cm, weight 73 ± 11 kg, VO2peak 37.7 ± 4.1 mL/min/kg) that trained 1.7 ± 0.3 times per week over 12 weeks (70 min 4 v 4 handball sessions) or an inactive control group (CG; n = 14, 169 ± 5 cm, 71 ± 12 kg, 38.1 ± 3.7 mL/min/kg). Physiological and psychological and motivational training adaptations were assessed pre- and post-intervention by dual-energy X-ray Absorptiometry (DXA) scans, blood sampling, physical tests, and questionnaires. Results: The average heart rate (HR) over all training sessions was equal to 85% ± 6% HRmax. Between-group intervention effects were observed in favor of HG for muscle mass (2.1%, p = 0.024), proximal femur bone mineral density (0.8%, p = 0.041), Yo-Yo IE1 intermittent endurance test level 1 (IE1) performance (35%, p < 0.001), and incremental treadmill test performance (11.5%, p = 0.003), but not total fat mass (p = 0.176), mean arterial blood pressure (p = 0.328), resting HR (p = 0.219), or blood lipids (p = 0.298–0.854). In CG, no changes were observed in any of the measured physiological variables after the training period. Compared to CG, HG had an increase in intrinsic motivation (p < 0.001) and in the well-being subscale “energy” (p = 0.010). Conclusion: Participation in regular recreational team handball training organized as small-sided games has marked beneficial effects on physical performance, musculoskeletal fitness, well-being, and motivation in untrained young women. Keywords: Bone mineral density (BMD), Intensity, Intermittent, Motivation, Muscle mass, Physical performance, Recreational handball, Well-bein

Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer.

Keratins are the main identification markers of circulating tumor cells (CTCs); however, whether their deregulation is associated with the metastatic process is largely unknown. Previously we have shown by in silico analysis that keratin 16 (KRT16) mRNA upregulation might be associated with more aggressive cancer. Therefore, in this study, we investigated the biological role and the clinical relevance of K16 in metastatic breast cancer. By performing RT-qPCR, western blot, and immunocytochemistry, we investigated the expression patterns of K16 in metastatic breast cancer cell lines and evaluated the clinical relevance of K16 expression in CTCs of 20 metastatic breast cancer patients. High K16 protein expression was associated with an intermediate mesenchymal phenotype. Functional studies showed that K16 has a regulatory effect on EMT and overexpression of K16 significantly enhanced cell motility (p < 0.001). In metastatic breast cancer patients, 64.7% of the detected CTCs expressed K16, which was associated with shorter relapse-free survival (p = 0.0042). Our findings imply that K16 is a metastasis-associated protein that promotes EMT and acts as a positive regulator of cellular motility. Furthermore, determining K16 status in CTCs provides prognostic information that helps to identify patients whose tumors are more prone to metastasize

EPAC-Lung:Pooled analysis of circulating tumor cells in advanced non-small cell lung cancer

Background: We assessed the clinical validity of circulating tumor cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a European pooled analysis of individual patient data. This is the largest study of its kind and the first to examine between-centre heterogeneity of CTC identification in NSCLC.Methods: Nine European NSCLC CTC centers were asked to provide reported/unreported anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 - March 2017. We used Cox regression models, stratified by centre, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinico-pathological models using likelihood ratio (LR) statistics and c-indices.Results: Seven out of nine eligible centers provided data for 550 eligible patients, including 209 patients whose prognostic information was previously unpublished. CTC counts of ≥ 2 and ≥5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: HR 1.72, p &lt; 0·001; ≥5 CTCs: HR 2.21, p &lt; 0·001) and overall survival (≥2 CTCs: HR 2·18, p &lt; 0·001; ≥5 CTCs: HR 2·75, p &lt; 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinico-pathological models (log-transformed CTCs p &lt; 0·0001; ≥2 CTCs p &lt; 0·0001; ≥5 CTCs p &lt; 0·0001), while more moderate improvements were observed with the use of c-index models. There was minor evidence of between-center heterogeneity in the effect on PFS, but not OS.No difference in CTC profile was observed between key NSCLC molecular subsets such as EGFR, ALK, and KRAS.Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC. CTC count improves prognostication when added to full clinico-pathological predictive models. ≥2 CTCs is an appropriate cutoff to move towards establishing clinical utility

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

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

Clonality of circulating tumor cells in breast cancer brain metastasis patients

BACKGROUND: The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. METHODS: Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). RESULTS: CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. CONCLUSION: The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment

DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure

Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1–p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer