Lactoferrin quantification in cattle faeces by ELISA

Background: Promoting and maintaining health is critical to ruminant welfare and productivity. Within human medicine, faecal lactoferrin is quantified for routine assessment of various gastrointestinal illnesses avoiding the need for blood sampling. This approach might also be adapted and applied for non-invasive health assessments in animals. Methods: In this proof-of-concept study, a bovine lactoferrin enzyme-linked immunosorbent assays (ELISA), designed for serum and milk, was applied to a faecal supernatant to assess its potential for quantifying lactoferrin in the faeces of cattle. Faecal lactoferrin concentrations were compared to background levels to assess the viability of the technique. A comparison was then made against serum lactoferrin levels to determine if they were or were not reflective of one another. Results: The optical densities of faecal samples were significantly greater than background readings, supporting the hypothesis that the assay was effective in quantifying faecal lactoferrin (T13, 115 = 11.99, p < 0.0005). The mean faecal lactoferrin concentration was 0.269 µg mL−1 (S.E. 0.031) and the mean serum concentration 0.074 µg mL−1 (S.E. 0.005). Lactoferrin concentrations of faecal and serum samples, taken from the same animals on the same day, were significantly different (T21 = 2.20, p = 0.039) and did not correlate (r = 0.2699, p = 0.238). Conclusion: Results support the hypothesis that lactoferrin can be quantified in cattle faeces by ELISA. Whilst further research is required to determine the physiological source of the lactoferrin, this highlights the potential of the method for non-invasive assessment of cattle immunology and pathology

Chemotherapy for advanced breast cancer: what influences oncologists' decision-making?

Chemotherapy is widely used in the management of patients with advanced breast cancer. However, a considerable proportion of patients experience toxic side effects without gaining benefit. This study aimed to elicit oncologists' views of the goals of chemotherapy for patients with advanced breast cancer and to elicit which factors are important in decisions to recommend chemotherapy to such patients. 30 oncologists underwent a semi-structured interview to examine their views of 5 goals of chemotherapy and of various disease, treatment and patient-related factors that might influence decisions to offer treatment. The clinicians also made decisions regarding treatment in relation to a hypothetical patient scenario under varying clinical conditions. Relief of symptoms and improvement of activity were rated as the most valuable and achievable goals of treatment. The patient's performance status, frailty and their wishes regarding treatment were the most important patient-related factors in determining decision-making. The most important disease/treatment-related factors were pace of the disease, previous poor response to chemotherapy, co-existing symptoms and concurrent medical conditions. The hypothetical scenario revealed that co-existing medical conditions, adverse previous response, increased age and depression would decrease the likelihood of recommending chemotherapy, whereas key symptoms (e.g. breathlessness) and the patient's goals would increase the likelihood. The findings suggest that British oncologists primarily aim to improve patients' physical function, although subjective factors, such as a patient's desire for anti-cancer treatment and their future goals, also influence decisions to offer treatment. © 2001 Cancer Research Campaign http://www.bjcancer.co

Automated psychological therapy using immersive virtual reality for treatment of fear of heights: A single-blind, parallel-group, randomised controlled trial

Background Engaging, interactive, and automated virtual reality (VR) treatments might help solve the unmet needs of individuals with mental health disorders. We tested the efficacy of an automated cognitive intervention for fear of heights guided by an avatar virtual coach (animated using motion and voice capture of an actor) in VR and delivered with the latest consumer equipment. Methods We did a randomised trial of automated VR versus usual care. We recruited adults aged older than 18 years with a fear of heights by radio advertisements in Oxfordshire, UK. We diagnosed fear of heights if participants scored more than 29 on the Heights Interpretation Questionnaire (HIQ). We randomly allocated participants by computer in a 1:1 ratio to either automated VR delivered in roughly six 30-min sessions administered about two to three times a week over a 2-week period (intervention group) or to usual care (control group). Randomisation was stratified by severity of fear of heights. The research team, who were unaware of the random allocation, administered three fear-of-height assessments, at baseline (0 weeks), at the end of treatment (2 weeks), and at follow-up (4 weeks). The primary outcome measure was HIQ score (range 16–80, with higher scores indicating greater severity). This trial is registered with the ISRCTN registry, number ISRCTN11898283. Findings Between Nov 25, 2017, and Feb 27, 2018, 100 individuals were enrolled and underwent randomisation, of whom 49 were assigned to the VR treatment group and 51 to the control group. All participants completed the 4-week follow-up. The mean total treatment time in VR was 124·43 min (SD 34·23). Compared with participants in the control group, the VR treatment reduced fear of heights at the end of treatment (mean change score −24·5 [SD 13·1] in the VR group vs −1·2 [7·3] in the control group; adjusted difference −24·0, 95% CI −27·7 to −20·3; Cohen's d=2·0; p<0·0001). The benefit was maintained at follow-up (mean change score −25·1 [SD 13·9] in the VR group vs −1·5 [7·8] in the control group; adjusted difference −24·3, 95% CI −27·9 to −20·6; Cohen's d=2·0; p<0·0001). The number needed to treat to at least halve the fear of heights was 1·3. No adverse events were reported. Interpretation Psychological therapy delivered automatically by a VR coach can produce large clinical benefits. Evidence-based VR treatments have the potential to greatly increase treatment provision for mental health disorders

Desire thinking as a predictor of drinking status following treatment for alcohol use disorder: A prospective study

© 2019 Elsevier Ltd Research has indicated that craving is one of the strongest predictors of treatment outcome and relapse in Alcohol Use Disorders (AUD) but there is little consensus on the factors that may influence its activation and escalation. Research has also shown that desire thinking is an important cognitive process which may exacerbate craving in problem drinkers. The aim of present study was to explore, for the first time, the role of desire thinking in prospectively predicting relapse, craving and binge drinking in patients receiving treatment for AUD. One hundred and thirty-five patients admitted to two rehabilitation centres and two outpatient services for addiction and mental health problems were administered baseline, treatment completion and three months follow-up measures of anxiety and depression, AUD severity, binge drinking frequency, craving and desire thinking. Results indicated that the verbal perseveration component of desire thinking at treatment completion was the only significant predictor of relapse at follow-up over and above baseline AUD severity and binge drinking frequency. Furthermore, the imaginal prefiguration component of desire thinking and craving levels at treatment completion were found to predict craving levels at follow-up independently of AUD severity and binge drinking frequency at baseline. Finally, both the imaginal prefiguration and verbal perseveration components of desire thinking at treatment completion were found to be the only predictors of binge drinking frequency at follow-up independently of AUD severity and binge drinking frequency at baseline. Treatments for AUD should aim to reduce desire thinking in people to enhance clinical outcomes and reduce relapse risk

Structural outcomes in the Cleft Care UK study. Part 2:Dento-facial outcomes

OBJECTIVES: To compare facial appearance and dento-alveolar relationship outcomes from the CSAG (1998) and CCUK (2013) studies. SETTING AND SAMPLE POPULATION: Five-year-olds born with non-syndromic unilateral cleft lip and palate. Those in the original CSAG were treated in a dispersed model of care with low-volume operators. Those in CCUK were treated in a more centralized, high-volume operator model. MATERIALS AND METHODS: We compared facial appearance using frontal view photographs (252 CCUK, 239 CSAG) and dental relationships using study models (198 CCUK, 223 CSAG). Facial appearance was scored by a panel of six assessors using a standardized and validated outcome tool. Dento-alveolar relationships were scored by two assessors using the 5-Year-Olds’ Index. Ordinal regression was used to compare results between surveys. RESULTS: Excellent or good facial appearance was seen in 36.2% of CCUK compared with 31.9% in CSAG. In CCUK, 21.6% were rated as having poor or very poor facial appearance compared with 27.6% in CSAG. The percentage rated as having excellent or good dento-alveolar relationships was 53.0% in CCUK compared with 29.6% in CSAG. In CCUK, 19.2% were rated as having poor or very poor dento-alveolar relationships compared to 36.3% in CSAG. The odds ratios for improved outcome in CCUK compared to CSAG were 1.43 (95% CI 1.03, 1.97) for facial appearance and 2.29 (95% CI 1.47, 3.55) for dento-alveolar relationships. CONCLUSIONS: Facial and dento-alveolar outcomes were better in CCUK children compared to those in CSAG

Automated psychological therapy using immersive virtual reality for treatment of fear of heights:a single-blind, parallel-group, randomised controlled trial

Background: Engaging, interactive, and automated virtual reality (VR) treatments might help solve the unmet needs of individuals with mental health disorders. We tested the efficacy of an automated cognitive intervention for fear of heights guided by an avatar virtual coach (animated using motion and voice capture of an actor) in VR and delivered with the latest consumer equipment. Methods: We did a randomised trial of automated VR versus usual care. We recruited adults aged older than 18 years with a fear of heights by radio advertisements in Oxfordshire, UK. We diagnosed fear of heights if participants scored more than 29 on the Heights Interpretation Questionnaire (HIQ). We randomly allocated participants by computer in a 1:1 ratio to either automated VR delivered in roughly six 30-min sessions administered about two to three times a week over a 2-week period (intervention group) or to usual care (control group). Randomisation was stratified by severity of fear of heights. The research team, who were unaware of the random allocation, administered three fear-of-height assessments, at baseline (0 weeks), at the end of treatment (2 weeks), and at follow-up (4 weeks). The primary outcome measure was HIQ score (range 16–80, with higher scores indicating greater severity). This trial is registered with the ISRCTN registry, number ISRCTN11898283. Findings: Between Nov 25, 2017, and Feb 27, 2018, 100 individuals were enrolled and underwent randomisation, of whom 49 were assigned to the VR treatment group and 51 to the control group. All participants completed the 4-week follow-up. The mean total treatment time in VR was 124·43 min (SD 34·23). Compared with participants in the control group, the VR treatment reduced fear of heights at the end of treatment (mean change score −24·5 [SD 13·1] in the VR group vs −1·2 [7·3] in the control group; adjusted difference −24·0, 95% CI −27·7 to −20·3; Cohen's d=2·0; p&lt;0·0001). The benefit was maintained at follow-up (mean change score −25·1 [SD 13·9] in the VR group vs −1·5 [7·8] in the control group; adjusted difference −24·3, 95% CI −27·9 to −20·6; Cohen's d=2·0; p&lt;0·0001). The number needed to treat to at least halve the fear of heights was 1·3. No adverse events were reported. Interpretation: Psychological therapy delivered automatically by a VR coach can produce large clinical benefits. Evidence-based VR treatments have the potential to greatly increase treatment provision for mental health disorders.</p

Pseudo-single crystal electrochemistry on polycrystalline electrodes : visualizing activity at grains and grain boundaries on platinum for the Fe2+/Fe3+ redox reaction

The influence of electrode surface structure on electrochemical reaction rates and mechanisms is a major theme in electrochemical research, especially as electrodes with inherent structural heterogeneities are used ubiquitously. Yet, probing local electrochemistry and surface structure at complex surfaces is challenging. In this paper, high spatial resolution scanning electrochemical cell microscopy (SECCM) complemented with electron backscatter diffraction (EBSD) is demonstrated as a means of performing ‘pseudo-single-crystal’ electrochemical measurements at individual grains of a polycrystalline platinum electrode, while also allowing grain boundaries to be probed. Using the Fe2+/3+ couple as an illustrative case, a strong correlation is found between local surface structure and electrochemical activity. Variations in electrochemical activity for individual high index grains, visualized in a weakly adsorbing perchlorate medium, show that there is higher activity on grains with a significant (101) orientation contribution, compared to those with (001) and (111) contribution, consistent with findings on single-crystal electrodes. Interestingly, for Fe2+ oxidation in a sulfate medium a different pattern of activity emerges. Here, SECCM reveals only minor variations in activity between individual grains, again consistent with single-crystal studies, with a greatly enhanced activity at grain boundaries. This suggests that these sites may contribute significantly to the overall electrochemical behavior measured on the macroscale

Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy

Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca(2+) handling is a key feature of HF pathophysiology. Restoring the Ca(2+) regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp(−/−)), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF