Visual assessment of body condition and skin soiling in cattle by professionals and undergraduate students using photo slides

We aimed to study to what extent body condition and skin soiling in cattle are rated differently depending on the profession, education and professional experience of assessors. Data were collected at 15 group-training sessions in the years 2009-2016. Totally, 569 persons; Swedish animal welfare inspectors, veterinarians/advisers, animal welfare scientists, other animal professionals as well as undergraduate students in animal science rated a set of 6-40 photos with respect to animal body condition, animal skin soiling, and recommended corrective action in response to perceived animal soiling. The more extensive animal science education, the less prone animal welfare inspectors were to give higher body condition scores. Students had a higher overall probability of rating the degree of soiling higher than the animal welfare inspectors and veterinarians/advisers. Students also recommended stricter corrective actions than did welfare inspectors and veterinarians/advisers, and veterinarians/advisers recommended less strict actions than animal welfare inspectors

Age-Related Olfactory Decline is Associated with the BDNF Val66met Polymorphism: Evidence from a Population-Based Study

The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70–90 years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45–65 years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance

Interval training compared with continuous training in patients with COPD

SummaryThe aim of this study was to compare the effects of interval training (3-min intervals) with continuous training on peak exercise capacity (W peak), physiological response, functional capacity, dyspnoea, mental health and health-related quality of life (HRQoL) in patients with moderate or severe COPD.Sixty patients exercised twice weekly for 16 weeks after randomisation to interval- or continuous training. Target intensity was ⩾80% of baseline W peak in the interval group (I-group) and ⩾65% in the continuous group (C-group). Patients were tested by spirometry, ergometer cycle test, cardiopulmonary test and a 12min walk test. Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease Questionnaire (CRDQ), mental health by Hospital Anxiety and Depression scale (HAD) and HRQoL by the Medical Outcomes Survey Short Form 36 (SF-36).After training, W peak, peak oxygen uptake (VO2 peak) and exhaled carbon dioxide (VCO2 peak) increased significantly in both groups, no significant differences between the groups. Minute ventilation (VE peak) increased only in the C-group. At identical work rates (isotime) VO2, VCO2 and VE were significantly more decreased in the I-group than in the C-group (p<0.05). Functional capacity, dyspnoea, mental health, and HRQoL improved significantly in both groups, no difference between the groups.Interval training and continuous training were equally potent in improving peak exercise capacity, functional exercise capacity, dyspnoea, mental health and HRQoL in patients with moderate or severe COPD. At isotime, the physiological response to training differed between the groups, in favour of the interval training

Predictors of fear of childbirth and depressive symptoms among pregnant women: a cross-sectional survey in Pwani region, Tanzania

Background: Many women experience fear of childbirth (FoB) and depressive symptoms (DS) during pregnancy, but little is known about FoB among Tanzanian women. The current study aimed to assess the prevalence of FoB and DS among pregnant women and determine predictors of each and both, focusing on sociodemographic and obstetric predictors. Methods: A cross-sectional study was conducted at six health facilities in two districts in Tanzania between 2018 and 2019. In total, 694 pregnant women with gestational age between 32 and 40weeks and expecting vaginal delivery were consecutively recruited and assessed for FoB and DS. We collected data through interviews using 6 and 4-points Likert Scale of the Wijma Delivery Expectancy Questionnaire Version A and Edinburgh Postnatal Depression Scale, respectively. Women who scored ≥66 and≥10 were categorised as having FoB and DS, respectively. We performed multivariable logistic regression to investigate the predictors of FoB and DS. Results: The prevalence rates of FoB and DS among pregnant women were 15.1 and 17.7%, respectively. FoB and DS were more likely in women aged above 30 years [Adjusted Odds Ratio (AOR) 6.29, 95%CI 1.43–27.84] and in single mothers (AOR 2.57, 95%CI 1.14–5.78). Women with secondary education and above (AOR 0.22, 95%CI 0.05–0.99) and those who had given birth previously (AOR 0.27, 95% CI 0.09–0.87) were less likely to have FoB in combination with DS Women who had previous obstetric complications, and those who did not receive any social support from male partners in previous childbirth were more likely to have FoB and DS. FoB was strongly associated with DS (AOR 3.42, 95%CI 2.12–5.53). DS only was more common in women who had inadequate income (AOR 2.35, 95%CI 1.38–3.99) or had previously experienced a perineal tear (AOR 2.32, 95%CI 1.31–4.08). Conclusions: Not having a formal education, having only primary education, being aged above 30 years, being single, being nulliparous, having experienced obstetric complications, and having a lack of social support from a male partner during previous pregnancy and childbirth were predictors of FoB and DS during pregnancy. FoB and DS were strongly associated with each other. It is vital to identify at-risk women early, to ofer support during pregnancy and childbirth

Additive clinical impact of epidermal growth factor receptor and podocalyxin-like protein expression in pancreatic and periampullary adenocarcinomas

The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n=175) and (Cohort 2, n=189). The effect of TGF-beta -induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.Peer reviewe

Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising treatment strategy. However, several high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which promotes inhibition of both p53/MDM2 (murine double minute 2) and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA (reactivation of p53 and induction of tumor cell apoptosis) and protoporphyrin IX (PpIX). Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions