Ropinirole eye drops induce vomiting effectively in dogs: a randomised, double-blind, placebo-controlled clinical study

There is a need for an effective and safe emetic agent that dog owners could easily administer to their dogs following veterinary advice in cases of potential poisoning. As a response to this need, a randomised, double-blind, multi-site, clinical field study was performed to assess the efficacy, safety and usability of ropinirole eye drops to induce vomiting in dogs. Ropinirole (target dose 3.75 mg/m2) was applied to eyes of 100 dogs, and 32 dogs received placebo. The drug was administered by the dog owner at a veterinary clinic under the supervision of a veterinarian and led to vomition in 95% of the ropinirole-treated dogs within 30 min. The median time to first vomit was 10 min (range: 3–37 min). None of the dogs receiving placebo vomited in this time period. All owners were able to administer the product and 96% of them assessed the administration to be very easy or easy, which was confirmed by the observing veterinarian. Some ocular signs were seen both with ropinirole and placebo, hyperaemia being the most common. All observed signs were transient and in most cases mild. Ropinirole eye drops provided an effective, safe and reliable means to induce emesis in dogs

Review : Alternative and novel feeds for ruminants: nutritive value, product quality and environmental aspects

Ruminant-based food production faces currently multiple challenges such as environmental emissions, climate change and accelerating food-feed-fuel competition for arable land. Therefore, more sustainable feed production is needed together with the exploitation of novel resources. In addition to numerous food industry (milling, sugar, starch, alcohol or plant oil) side streams already in use, new ones such as vegetable and fruit residues are explored, but their conservation is challenging and production often seasonal. In the temperate zones, lipid-rich camelina (Camelina sativa) expeller as an example of oilseed by-products has potential to enrich ruminant milk and meat fat with bioactive trans-11 18:1 and cis-9,trans-11 18:2 fatty acids and mitigate methane emissions. Regardless of the lower methionine content of alternative grain legume protein relative to soya bean meal (Glycine max), the lactation performance or the growth of ruminants fed faba beans (Vicia faba), peas (Pisum sativum) and lupins (Lupinus sp.) are comparable. Wood is the most abundant carbohydrate worldwide, but agroforestry approaches in ruminant nutrition are not common in the temperate areas. Untreated wood is poorly utilised by ruminants because of linkages between cellulose and lignin, but the utilisability can be improved by various processing methods. In the tropics, the leaves of fodder trees and shrubs (e.g. cassava (Manihot esculenta), Leucaena sp., Flemingia sp.) are good protein supplements for ruminants. A food-feed production system integrates the leaves and the by-products of on-farm food production to grass production in ruminant feeding. It can improve animal performance sustainably at smallholder farms. For larger-scale animal production, detoxified jatropha (Jatropha sp.) meal is a noteworthy alternative protein source. Globally, the advantages of single-cell protein (bacteria, yeast, fungi, microalgae) and aquatic biomass (seaweed, duckweed) over land crops are the independence of production from arable land and weather. The chemical composition of these feeds varies widely depending on the species and growth conditions. Microalgae have shown good potential both as lipid (e.g. Schizochytrium sp.) and protein supplements (e.g. Spirulina platensis) for ruminants. To conclude, various novel or underexploited feeds have potential to replace or supplement the traditional crops in ruminant rations. In the short-term, N-fixing grain legumes, oilseeds such as camelina and increased use of food and/or fuel industry by-products have the greatest potential to replace or supplement the traditional crops especially in the temperate zones. In the long-term, microalgae and duckweed of high-yield potential as well as wood industry by-products may become economically competitive feed options worldwide.Peer reviewe

Personalized drug sensitivity screening for bladder cancer using conditionally reprogrammed patient-derived cells

Many patients with muscle-invasive bladder cancer (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals’ drug sensitivities. We investigated the suitability of conditionally reprogrammed (CR) cells for the characterization of BC properties and their feasibility for personalized drug sensitivity screening. The CR cultures were established from six BC tumors with varying histology and stage. Four cultures were successfully propagated for genomic, transcriptomic, and protein expression profiling and compared to the parental tumors. Two out of four CR cultures (urothelial carcinoma and small cell neuroendocrine carcinoma [SmCC]) corresponded well to their parental tumors and underwent drug sensitivity screening to identify novel drugs for the respective tumors. Both cultures were sensitive to standard BC chemotherapy agents (eg cisplatin and gemcitabine) and to conventional drugs such as taxanes and inhibitors of topoisomerase and proteasome. The SmCC cells were also sensitive to statins (eg, atorvastatin and pitavastatin). In summary, after confirming their representativeness and origin, we conclude that CR cells are a feasible platform for personalized drug sensitivity testing and might thus add to the approaches used to personalize BC treatment strategies

The effect of partial substitution of rapeseed meal and faba beans by Spirulina platensis microalgae on milk production, nitrogen utilization, and amino acid metabolism of lactating dairy cows

Alternative protein sources such as microalgae and faba beans may have environmental benefits over rapeseed. We studied the effects of rapeseed meal (RSM) or faba beans (FB) as a sole protein feed or as protein feeds partially substituted with Spirulina platensis (spirulina) microalgae on milk production, N utilization, and AA metabolism of dairy cows. Eight multiparous Finnish Ayrshire cows (113 +/- 36.3 d in milk; mean +/- SD) were used in a balanced, replicated 4 x 4 Latin square with 2 x 2 factorial arrangement of treatments and 21-d periods. Four cows in one Latin square were rumen cannulated. Treatments were 2 isonitrogenously fed protein sources, RSM or rolled FB, or one of these sources with half of its crude protein substituted by spirulina (RSM-SPI and FB-SPI). Cows had ad libitum access to total mixed rations consisting of grass silage, barley, sugar beet pulp, minerals, and experimental protein feed. The substitution of RSM with FB did not affect dry matter intake (DMI) but decreased neutral detergent fiber intake and increased the digestibility of other nutrients. Spirulina in the diet decreased DMI and His intake. Spirulina had no effect on Met intake in cows on RSM diets but increased it in those on FB diets. Energy-corrected milk (ECM) and protein yields were decreased when RSM was substituted by FB. Milk and lactose yields were decreased in cows on the RSM-SPI diet compared with the RSM diet but increased in those on FB-SPI compared with FB. The opposite was true for milk fat and protein concentrations; thus, spirulina in the diet did not affect ECM. Feed conversion efficiency (ECM: DMI) increased in cows on FB diets with spirulina, whereas little effect was observed for those on RSM diets. The substitution of RSM by FB decreased arterial concentration of Met and essential AA. Spirulina in the diet increased milk urea N and ruminal NH4-N and decreased the efficiency of N utilization in cows on RSM diets, whereas those on FB diets showed opposite results. Met likely limited milk production in cows on the FB diet as evidenced by the decrease in arterial Met concentration and milk protein yield when RSM was substituted by FB. The results suggest the potential to improve milk production response to faba beans with supplementation of Met-rich feeds such as spirulina. This study also confirmed spirulina had poorer palatability than RSM and FB despite total mixed ration feeding and lower milk production when spirulina partially replaced RSM.Peer reviewe

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Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins : A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer

Background Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group >= 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI). Purpose To develop and validate radiomics and kallikrein models for the detection of csPCa. Study Type Retrospective. Population A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated. Field strength/Sequence A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI. Assessment In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores. Statistical Tests For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant. Results The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488). Data Conclusion The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains. Level of Evidence 1 Technical Efficacy Stage 2Peer reviewe

Internet-assisted cognitive behavioural therapy with telephone coaching for anxious Finnish children aged 10-13 years: study protocol for a randomised controlled trial

AbstractIntroductionChildhood anxiety is common, causes significant functional impairment and may lead to psychosocial problems by adulthood. Although cognitive behavioural therapy (CBT) is effective for treating anxiety, its availability is limited by the lack of trained CBT therapists and easily accessible local services. To address the challenges in both recognition and treatment, this study combines systematic anxiety screening in the general population with a randomised controlled trial (RCT) on internet-assisted CBT (ICBT) with telephone coaching. Child, family and intervention-related factors are studied as possible predictors or moderators, together with the COVID-19 pandemic.Methods and analysisThe study is an open two-parallel group RCT, stratified by sex, that compares ICBT with telephone coaching to an education control. Children aged 10–13 are screened at yearly school healthcare check-ups using five items from the Screen for Child Anxiety Related Disorders (SCARED) Questionnaire. The families of children who screen positive for anxiety are contacted to assess the family’s eligibility for the RCT. The inclusion criteria include scoring at least 22 points in the 41-item SCARED Questionnaire. The primary outcome is the SCARED child and parent reports. The secondary outcomes include the impact of anxiety, quality of life, comorbidity, peer relationships, perceptions of school, parental well-being and service use. Additional measures include demographics and life events, anxiety disorder diagnoses, as well as therapeutic partnerships, the use of the programme and general satisfaction among the intervention group.Ethics and disseminationThe study has been approved by the research ethics board of the Hospital District of South West Finland and local authorities. Participation is voluntary and based on informed consent. The anonymity of the participants will be protected and the results will be published in a scientific journal and disseminated to healthcare professionals and the general public.Trial registration number ClinicalTrials.gov NCT03310489, pre-results, initially released on 30 September 2017.</p

Effects of dry period energy intake on insulin resistance, metabolic adaptation, and production responses in transition dairy cows on grass silage-based diets

High energy intake in the dry period has reportedly had adverse effects on mobilization of body reserves, dry matter intake, and productivity of dairy cows. We investigated whether grass silage (GS) fed ad libitum (high energy intake, HEI; 141% of daily metabolizable energy requirements) in an 8-wk dry period affects metabolic adaptation-specifically, peripheral insulin resistance-compared with a total mixed ration consisting of GS, wheat straw, and rapeseed meal (55/40/5%; controlled energy intake, CEI; 108% of metabolizable energy/d) fed ad libitum. Multiparous Ayrshire dairy cows (n = 16) were used in a randomized complete block design until 8 wk after parturition. Commercial concentrates were fed 1 and 2 kg/d during the last 10 to 6 and 5 to 0 d before the expected calving date, respectively. Postpartum, a similar lactation diet with ad libitum access to GS and increasing concentrate allowance (maximum of 16 kg/d) was offered to all. The HEI group gained more body weight and had higher plasma insulin, glucose, and beta-hydroxybutyrate concentrations than the CEI group prepartum. Postpartal plasma glucose tended to be higher and milk yield was greater from wk 5 onward for HEI compared with CEI cows. An intravenous glucose tolerance test (IVGTT) was performed at -13 +/- 5 d and 9 +/- 1 d relative to calving. The HEI cows had greater insulin response to glucose load and smaller area under the response curve for glucose than CEI cows in prepartal IVGTT. Thus, compensatory insulin secretion adapted to changes in insulin sensitivity of the peripheral tissues, preserving glucose tolerance of HEI cows. Higher insulin levels were needed in HEI cows than in CEI cows to elicit a similar decrement of nonesterified fatty acid concentration in prepartal wurr, suggesting reduced inhibition of lipolysis by insulin in HEI cows before parturition. In conclusion, high energy intake of moderately digestible GS with low concentrate feeding in the close-up dry period did not have adverse effects on metabolic adaptation, insulin sensitivity, and body mobilization after parturition. Instead, this feeding regimen was more beneficial to early-lactation performance than GS-based total mixed ration diluted with wheat straw.Peer reviewe

How to read biparametric MRI in men with a clinical suspicious of prostate cancer: Pictorial review for beginners with public access to imaging, clinical and histopathological database

Prostate Magnetic Resonance Imaging (MRI) is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). Performing prostate MRI without the use of an intravenous contrast (IV) agent in men with a clinical suspicion of PCa can lead to reduced MRI scan time. Enabling a large array of different medical providers (from mid-level to specialized radiologists) to evaluate and potentially report prostate MRI in men with a clinical suspicion of PCa with a high accuracy could be one way to enable wide adoption of prostate MRI in men with a clinical suspicion of PCa. The aim of this pictorial review is to provide an insight into acquisition, quality control and reporting of prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa, aimed specifically at radiologists starting reporting prostate MRI, urologists, urology/radiology residents and mid-level medical providers without experience in reporting prostate MRI. Free public access (http://petiv.utu.fi/improd/and http://petiv.utu.fi/multiimprod/) to complete datasets of 161 and 338 men is provided. The imaging datasets are accompanied by clinical, laboratory and histopathological findings. Several topics are simplified in order to provide a solid base for the development of skills needed for an unsupervised review and potential reporting of prostate MRI in men with a clinical suspicion of PCa. The current review represents the first step towards enabling a large array of different medical providers to review and report accurately prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa

Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer: A prospective multi-institutional trial

Background: Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption.Methods and findings: The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score >= 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings.Conclusions: IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.</p