Liver fluke in beef cattle - Impact on production efficiency and associated greenhouse gas emissions estimated using causal inference methods.

We aimed to estimate 1) the marginal effect of liver fluke (Fasciola hepatica) infection on productivity of Scottish beef cattle, and 2) the associated greenhouse gas emissions intensity (GHG EI). Data comprised 240,065 abattoir records from NE Scotland from 2014 to 2017, including the presence or absence of lesions typical of liver fluke in the liver at the time of slaughter, from which we inferred liver fluke infection status. The retrospective analysis of abattoir records to estimate marginal effects of an exposure is complicated by the multi-dimensional, clustered nature of the datasets, which result in confounding of potential causal factors with the exposure. Causal inference methods are required to identify and correct for variation in background exposure. We constructed directed acyclic graphs (DAGs) of observed variables, including the potential confounders, breed, sex, breeder, finisher, season of birth and year of birth. We then applied inverse probability weighting (IPW) to adjust for variation among exposure risk and applied a doubly robust generalized linear model (DRGLM) to the weighted observations to estimate the marginal effect of fluke on the growth rate of animals and total days from birth until slaughter. We compared these estimates with the results of linear mixed effects (LME) models with the same variables, treating breeder and producer as random effects. To estimate GHG EI, we applied IPCC tier-2 type GHG calculations to the marginal effects estimated from IPW with DRGLM. The IPW with DRGLM model estimated that animals with active fluke lesions (adult fluke seen on postmortem inspection) gained 17 (95 % CI 12-22) g/d less saleable beef than animals with no lesions and no visible fluke. Animals with active fluke lesions were 11 (95 % CI 6.5-15) d older at slaughter weight than animals with no lesions. Animals with historic lesions in which there was scarring of the liver but in which no adult fluke were seen showed a wide variation in effect estimates, consistent with some misclassification. The effect estimates from LME models suggested slightly lower effects of fluke on growth rate and days to slaughter but with overlapping 95 % confidence intervals. Calculation of the associated GHG emissions suggest the EI of meat from a herd with no fluke is approximately 1.5 % lower than the same herd with fluke. Sustainably controlling liver fluke would have additional production benefits not included in this estimate and could therefore have a much greater impact on GHG EI in practice than demonstrated here.

Evaluation of amoxicillin, metronidazole and gentamicin dosage regimens for use in antibiotic prophylaxis in colorectal surgery.

OBJECTIVES: To evaluate amoxicillin, metronidazole and gentamicin dosage regimens for antibiotic prophylaxis in colorectal surgery. METHODS: The study was conducted in 20 patients undergoing colorectal surgery. Patients received one or two doses of amoxicillin 1000 mg, metronidazole 500 mg and gentamicin 3 mg/kg ideal body weight, banded by height. Antibiotic concentrations were measured up to 7 h post dose. Population pharmacokinetic (PopPK) analysis with NONMEM followed by Monte Carlo simulation of different dosage regimens was used to estimate the PTA for potential organisms associated with surgical site infections (SSIs). RESULTS: A median of 5 (range 3-6) concentrations were available per patient. CL and V of all antibiotics were related to weight; gentamicin CL was also related to CLCR. The administered doses maintained the desired PTA up to 8 h for the Streptococcus anginosus group but not for enterococci, Bacteroides fragilis group, MSSA, and Escherichia coli. An additional 500 mg amoxicillin every 4 h was sufficient to achieve the PTA for most relevant organisms but 2 hourly dosing was required for patients at risk of infective endocarditis. A metronidazole dose of 1000 mg was required for patients >85 kg. In patients with CLCR >50 mL/min, 5 mg/kg gentamicin (with an additional 2.5 mg/kg in prolonged surgery at 6 h) maintained PTA targets for >10 h. CONCLUSIONS: PopPK analysis with Monte Carlo simulation identified prophylactic antibiotic regimens that would maintain the PTA for organisms associated with SSIs during short- and long-duration colorectal surgery.

Short communication: Identifying key parameters for modelling the impacts of livestock health conditions on greenhouse gas emissions.

Improved animal health can reduce greenhouse gas (GHG) emissions intensity in livestock systems while increasing productivity. Integrated modelling of disease impacts on farm-scale emissions is important in identifying effective health strategies to reduce emissions. However, it requires that modellers understand the pathways linking animal health to emissions and how these might be incorporated into models. A key barrier to meeting this need has been the lack of a framework to facilitate effective exchange of knowledge and data between animal health experts and emissions modellers. Here, these two communities engaged in workshops, online exchanges and a survey to i) identify a comprehensive list of disease-related model parameters and ii) test its application to evaluating models. Fifty-six parameters were identified and proved effective in assessing the potential of farm-scale models to characterise livestock disease impacts on GHG emissions. Easy wins for the emissions models surveyed include characterising disease impacts related to feeding.

The Stirling Protocol - Putting the environment at the heart of prosperity and social inclusion.

While the global coronavirus crisis impacts society and the economy in a myriad of ways, it provides, what is likely to be, a once in a lifetime opportunity for us to rethink our response to climate change. According to the 2020 Global Risk Register, extreme weather and climate action failure are the two most likely and impactful risks to the global economy, which now more than ever needs to be avoided. Addressing the major challenges that we face from climate change can often appear to conflict with economic priorities. Add to this the fact that environmental mitigation steps can inadvertently exclude sections of the population and the enormity and complexity of climate change responses can result in paralysis. In contrast, the Stirling Protocol provides the framework for rapid, effective action and comprises three pillars: Environment, Economy & Inclusion. By addressing and balancing these three pillars, the simple protocol can be adopted throughout organisations putting the environment at the heart of sustainable prosperity and inclusion and provide a benchmark for positive action.

Net benefits of smallholder dairy cattle farms in Senegal can be significantly increased through the use of better dairy cattle breeds and improved management practices.

Senegal, located in West Africa, is an example of a low- to middle-income country where the government has prioritized improving livestock production self-sufficiency, with a strong focus on dairy. Among other initiatives, the use of exotic dairy cattle has been promoted, despite no evidence for the potential livelihood benefits (or otherwise) to smallholder farmers on adopting the new genetics. The current work fills this evidence gap by performing a farm-level economic study comparing the keeping of different breed and cross-breed types of dairy cattle under different management levels. Data for the study were obtained by monitoring 220 smallholder dairy cattle farms, with a combined cattle population of about 3,000 animals, over an almost 2-yr period. Findings of the study suggest that the most net-beneficial and cost-beneficial dairy cattle enterprise that could be used by the smallholder farmers was to keep crossbred indigenous zebu by exotic Bos taurus animals under management standards that are considered good compared with local standards. This dairy enterprise type was 7.4-fold more net beneficial and had a 1.4-fold more favorable cost-benefit ratio than the traditional system of keeping indigenous zebu animals under poor (low-input) management. Interestingly, the keeping of (near) pure B. taurus dairy cattle resulted in the highest milk yields and thus benefit from milk, but was not the most net beneficial due to the high costs of keeping these animals, particularly in terms of feed. We also found that increasing the management level of any of the breed or cross-breed types under consideration, including the indigenous zebu animals, resulted in an increased net benefit of 2.2- to 2.9-fold. Results of this economic analysis are discussed as part of a broader trade-off analysis, resulting in recommendations to strengthen the Senegal dairy sector. The combined intervention of improved dairy cattle genetics and management is considered a promising intervention to improve livelihoods of the rural poor as well as livestock production self-sufficiency for Senegal; some other system constraints are addressed.

Exploring the landscape of livestock 'Facts'.

The role of livestock in supporting human well-being is contentious, with different perceptions leading to polarised opinions. There is increasing concern about the health and environmental impacts of a high rate of consumption of livestock products in high-income countries. These concerns are heightened by an increase in consumption in middle-income countries. On the other hand, livestock support the livelihoods of many people, particularly in low income countries. The benefits of livestock for poor livestock keepers are multiple, including the important role livestock play in supporting crop production in mixed systems, in supplying nutrients and income, and in fulfilling cultural roles. In addition livestock can provide resilience against economic and climate shocks. In view of these apparent positive and negative impacts, the role of livestock in human wellbeing is highly contested, with arguments 'for' or 'against' sometimes distorted by vested interests or misinterpretation of evidence. The Livestock Fact Check project, undertaken by the Livestock Data for Decisions community of practice, has investigated several ideas concerning livestock commonly taken as 'fact'. By exploring the provenance of these 'facts' we highlight their importance and the risks of both misinterpreting them or using them out of context. Despite the diversity of the livestock sector resulting in equally diverse viewpoints, the project calls for participants in the livestock discourse to adopt a nuanced appreciation of global livestock systems. Judgement of livestock's role in global sustainable diets should be based on clear and well-interpreted information.

Effects of the Sex Ratio and Socioeconomic Deprivation on Male Mortality.

We explored relationships between male mortality and the sex ratio. (We tested relationships across 142 societies and in longitudinal data from Scotland. A male-biased sex ratio was associated with reduced mortality by intentional self-harm across 142 societies. This was replicated in longitudinal Scottish data, and men were less likely to die by suicide and assault when there were more men in the population only when levels of unemployment were low. We argue that this is consistent with a theoretical model in which men increase investment in relationships and offspring as "competition" under a male-biased sex ratio, and that the conflicting results of previous work may stem from divergent effects of the sex ratio on mortality depending upon relative deprivation.

Potential emerging chemical risks in the food chain associated with substances registered under REACH.

A screening procedure for the identification of potential emerging chemical risks in the food and feed chain developed in a previous EFSA-sponsored pilot study was applied to 15021 substances registered under the REACH Regulation at the time of evaluation. Eligible substances were selected from this dataset by excluding (a) intermediates handled under strictly controlled conditions, (b) substances lacking crucial input data and (c) compounds considered to be outside the applicability domain of the models used. Selection of eligible substances resulted in a considerable reduction to 2336 substances. These substances were assessed and scored for environmental release (tonnage and use information from REACH registration dossiers), biodegradation (predictions from BIOWIN models 3, 5 and 6 evaluated in a battery approach), bioaccumulation in food/feed (ACC-HUMANsteady modelling) and chronic human health hazards (classification according to the CLP Regulation for carcinogenicity, mutagenicity, reproductive toxicity and repeated dose toxicity as well as IARC classification for carcinogenicity). Prioritisation based on the scores assigned and additional data curation steps identified 212 substances that are considered potential emerging risks in the food chain. Overall, 53% of these substances were prioritised due to chronic hazards identified in REACH registrations dossiers only (i.e. hazards not identified in classifications from other sources). Bioaccumulation in food and feed predicted on the basis of ACC-HUMANsteady modelling identified many substances that are not considered bioaccumulative in aquatic or terrestrial organisms based on screening criteria of the relevant ECHA guidance documents. Furthermore, 52% of the priority substances have not yet been assessed for their presence in food/feed by EU regulatory agencies. This finding and illustrative examples suggest that the screening procedure identified substances that have the potential to be emerging chemical risks in the food chain. Future research should investigate whether they actually represent emerging chemical risks as defined in EFSA's mandate.

Protocol for a systematic review and meta-analysis of data from preclinical studies employing forced swimming test: an update.

OBJECTIVE: Forced swimming test (FST) in rodents is a widely used behavioural test for screening antidepressants in preclinical research. Translational value of preclinical studies may be improved by appraisal of the quality of experimental design and risk of biases, which remains to be addressed for FST. The present protocol of a systematic review with meta-analysis aims to investigate the quality of preclinical studies employing FST to identify risks of bias in future publications. In addition, this protocol will help to determine the effect sizes (ES) for primary and secondary outcomes according to several aspects of the FST study design. SEARCH STRATEGY SCREENING ANNOTATION DATA MANAGEMENT: Publications reporting studies testing different classes of antidepressants in FST will be collected from Medline, SCOPUS and Web of Science databases. A broad list of inclusion criteria will be applied excluding those studies whereby FST is used as a stressor or studies reporting data from co-treatments. For assessing the quality of the included publications, the quality checklist adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by using the χ2statistic with n-1 degrees of freedom. Subgroup meta-analysis (meta-regression, and if necessary, stratified regression) will be performed when possible according to characteristics of study design and study quality to assess their impact on efficacy of the treatments. In addition, funnel plotting, Egger regression, and 'trim and fill' will be used to assess the risk of publication bias. Results of this protocol will help to create rational methodological guidelines for application of FST in rodents and improve the quality and translational value of preclinical research on antidepressant discovery. REPORTING: A preliminary version of the present protocol has been preregistered with Systematic Review Facility (http://syrf.org.uk/). A preprint version of the current protocol has been registered with Open Science Framework (https://osf.io/9kxm4/). Results will be communicated in scientific meetings and peer-reviewed journals. We plan to conduct an anonymous and online survey within the scientific community to ask researchers about their perception of risk of bias and their experience with the publication of negative results.

Development of a novel scoring system for identifying emerging chemical risks in the food chain.

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

The greenhouse gas abatement potential of productivity improving measures applied to cattle systems in a developing region.

Developing countries are experiencing an increase in total demand for livestock commodities, as populations and per capita demands increase. Increased production is therefore required to meet this demand and maintain food security. Production increases will lead to proportionate increases in greenhouse gas (GHG) emissions unless offset by reductions in the emissions intensity (Ei) (i.e. the amount of GHG emitted per kg of commodity produced) of livestock production. It is therefore important to identify measures that can increase production whilst reducing Ei cost-effectively. This paper seeks to do this for smallholder agro-pastoral cattle systems in Senegal; ranging from low input to semi-intensified, they are representative of a large proportion of the national cattle production. Specifically, it identifies a shortlist of mitigation measures with potential for application to the various herd systems and estimates their GHG emissions abatement potential (using the Global Livestock Environmental Assessment Model) and cost-effectiveness. Limitations and future requirements are identified and discussed. This paper demonstrates that the Ei of meat and milk from livestock systems in a developing region can be reduced through measures that would also benefit food security, many of which are likely to be cost-beneficial. The ability to make such quantification can assist future sustainable development efforts.

Invited review: A position on the Global Livestock Environmental Assessment Model (GLEAM).

The livestock sector is one of the fastest growing subsectors of the agricultural economy and, while it makes a major contribution to global food supply and economic development, it also consumes significant amounts of natural resources and alters the environment. In order to improve our understanding of the global environmental impact of livestock supply chains, the Food and Agriculture Organization of the United Nations has developed the Global Livestock Environmental Assessment Model (GLEAM). The purpose of this paper is to provide a review of GLEAM. Specifically, it explains the model architecture, methods and functionality, that is the types of analysis that the model can perform. The model focuses primarily on the quantification of greenhouse gases emissions arising from the production of the 11 main livestock commodities. The model inputs and outputs are managed and produced as raster data sets, with spatial resolution of 0.05 decimal degrees. The Global Livestock Environmental Assessment Model v1.0 consists of five distinct modules: (a) the Herd Module; (b) the Manure Module; (c) the Feed Module; (d) the System Module; (e) the Allocation Module. In terms of the modelling approach, GLEAM has several advantages. For example spatial information on livestock distributions and crops yields enables rations to be derived that reflect the local availability of feed resources in developing countries. The Global Livestock Environmental Assessment Model also contains a herd model that enables livestock statistics to be disaggregated and variation in livestock performance and management to be captured. Priorities for future development of GLEAM include: improving data quality and the methods used to perform emissions calculations; extending the scope of the model to include selected additional environmental impacts and to enable predictive modelling; and improving the utility of GLEAM output.

The impact of social deprivation on the response to a randomised controlled trial of a weight management intervention (BeWEL) for people at increased risk of colorectal cancer.

BACKGROUND: Although 45% of colorectal cancer (CRC) cases may be avoidable through appropriate lifestyle and weight management, health promotion interventions run the risk of widening health inequalities. The BeWEL randomised controlled trial assessed the impact of a diet and activity programme in overweight adults who were diagnosed with a colorectal adenoma, demonstrating a significantly greater weight loss at 12 months in intervention participants than in controls. The present study aimed to compare BeWEL intervention outcomes by participant deprivation status. METHODS: The intervention group of the BeWEL trial (n = 163) was classified by the Scottish Index of Multiple Deprivation (SIMD) quintiles into 'more deprived' (SIMD 1-2, n = 58) and 'less deprived' (SIMD 3-5, n = 105). Socio-economic and lifestyle variables were compared at baseline to identify potential challenges to intervention adherence in the more deprived. Between group differences at 12 months in primary outcome (change in body weight) and secondary outcomes (cardiovascular risk factors, diet, physical activity, knowledge of CRC risk and psychosocial variables) were assessed by deprivation status. RESULTS: At baseline, education (P = 0.001), income (P < 0.001), spending on physical activity (P = 0.003) and success at previous weight loss attempts (P = 0.007) were significantly lower in the most deprived. At 12 months, no between group differences by deprivation status were detected for changes in primary and main secondary outcomes. CONCLUSIONS: Despite potential barriers faced by the more deprived participants, primary and most secondary outcomes were comparable between groups, indicating that this intervention is unlikely to worsen health inequalities and is equally effective across socio-economic groups.

Predictors of heroin abstinence in opiate substitution therapy in heroin-only users and dual users of heroin and crack.

AIMS: To analyse predictors of heroin abstinence in opiate substitution therapy (OST) based on frequency of crack use and its interactions with other predictors in a clinical non-experimental setting. DESIGN: Retrospective study. SETTING: A community drug service in London, UK. PARTICIPANTS: 325 clients starting OST between 2010 and 2014 (197 methadone and 128 buprenorphine). MEASUREMENTS: Logistic regression models (a general model and separate models for methadone and buprenorphine) assessed demographic and clinical data as predictors of heroin abstinence at one year after treatment start (or at the date of transfer to another service). FINDINGS: For the general model participants choosing methadone were more likely to use heroin at follow up (OR=2.36, 95% CI: 1.40-3.17) as were daily crack users on methadone (OR=2.62, 95% CI: 0.96-7.16). For the methadone model only daily crack use predicted heroin use at follow up (OR=2.62, 95% CI: 0.96-7.16). For buprenorphine, higher amounts of baseline heroin use, lower buprenorphine dose and daily drinking predicted heroin use at follow up (OR=0.85, 95% CI: 0.75-0.95; OR=1.31, 95% CI: 1.06-1.60 and OR=6.04, 95% CI: 1.26-28.92). Both use of cannabis and depression increased likelihood of heroin abstinence for clients not using crack compared to occasional (OR=6.68, 95% CI: 0.37-119.59; OR=106.31, 95% CI: 3.41-3313.30) and daily (OR=57.49 (95% CI: 2.37-1396.46; OR=170.99 (95% CI: 4.61-6339.47) users. CONCLUSIONS: Most of the predictors in the general model were found significant only in the buprenorphine but not in the methadone model, suggesting that a general model has little predictive value. Crack use was a significant predictor of heroin abstinence at follow up in all models, however for buprenorphine only when depression or cannabis use was present. Further research is needed to assess effective treatment approaches for the growing population of dual users.

Integrating livestock health measures into marginal abatement cost curves.

Improving livestock health offers both private and social benefits. Among the potential social benefits is a reduction in the greenhouse gas (GHG) emissions arising from livestock production. Reductions in emissions intensity (the amount of GHG produced per kilogram of meat, milk or eggs) may occur, as improving health can lead to improvements in the parameters that emissions intensity is sensitive to, such as (for ruminants): maternal fertility and abortion rates, calf and lamb mortality rates and growth rates, milk yields and feed conversion rates. However, improved health is not yet widely recognised as a GHG mitigation measure due, in part, to difficulties in reliably quantifying the financial and GHG effects of disease control options. This paper discusses how the GHG effects of disease control can be quantified and included in a marginal abatement cost curve (MACC). To illustrate some of the challenges, it draws on the experience of including health measures in the most recent (2015) agricultural MACCs in the United Kingdom.

L'amélioration de la santé des animaux d'élevage apporte des bénéfices non seulement aux personnes et entreprises privées mais aussi à la société en général. La réduction des émissions de gaz à effet de serre est l'un des bénéfices potentiels apportés à la société par les élevages. Il est ainsi possible de réduire l'intensité des émissions (c'est-à-dire la quantité de gaz à effet de serre générée par kilogramme de viande, de lait ou d'oeufs), dans la mesure où l'amélioration de la santé animale s'accompagne d'une amélioration des paramètres qui influent sur l'intensité de ces émissions ; par exemple, chez les ruminants, le taux de fécondité, le taux d'avortements, le taux de mortalité néonatale et le taux de croissance chez les ovins et les caprins, la production de lait et le taux de conversion des aliments donnés aux animaux. Or, l'amélioration de la santé n'est pas toujours reconnue comme étant une mesure de réduction des gaz à effet de serre, en raison notamment de la difficulté de quantifier de manière fiable les effets des différentes stratégies zoosanitaires en termes financiers et d'émissions de gaz à effet de serre. Les auteurs proposent une méthode permettant de quantifier les effets des mesures de lutte contre les maladies animales sur les émissions de gaz à effet de serre et de les intégrer dans une courbe de coût marginal d'abattement. Afin d'illustrer certains enjeux en la matière, les auteurs présentent l'expérience conduite récemment (2015) au Royaume-Uni pour intégrer les mesures sanitaires dans les courbes de coût marginal d'abattement du secteur agricole.

El hecho de mejorar el estado de salud del ganado reporta beneficios de índole tanto privada como social. Entre los posibles beneficios sociales figura una reducción de las emisiones de gases de efecto invernadero resultantes de la producción pecuaria. Esas emisiones también pueden ser menos intensas (volumen de gases generados por kilogramo de carne, leche o huevos), pues la intensidad de las emisiones es sensible a una serie de parámetros cuyo valor mejora al hacerlo el estado de salud, tales como (en el caso de los rumiantes): tasas de fertilidad materna y de abortos; tasas de mortalidad y crecimiento en terneros y corderos; y tasas de producción de leche y de conversión alimenticia. Sin embargo, todavía no ha arraigado la idea de que la mejora del estado de salud es una medida de lucha contra los gases de efecto invernadero, debido en parte a las dificultades existentes para cuantificar con fiabilidad los efectos de los métodos de lucha zoosanitaria sobre parámetros económicos o sobre las emisiones. Los autores explican cómo cuantificar los efectos del control de enfermedades sobre los gases de efecto invernadero y a partir de ahí incluirlos en una curva del costo marginal de reducción. Para ilustrar algunos de los problemas que pueden surgir se refieren a la experiencia británica destinada a incluir parámetros que miden el estado de salud en las más recientes (2015) curvas del costo marginal de reducción en el ámbito agropecuario.

Prolactin receptors in Rip-cre cells, but not in AgRP neurones, are involved in energy homeostasis.

Among its many functions, prolactin has been implicated in energy homeostasis, particularly during pregnancy and lactation. The arcuate nucleus is a key site in the regulation of energy balance. The present study aimed to examine whether arcuate nucleus neuronal populations involved in energy homeostasis are prolactin responsive and whether they can mediate the effects of prolactin on energy homeostasis. To determine whether Agrp neurones or Rip-Cre neurones are prolactin responsive, transgenic mice expressing the reporter td-tomato in Agrp neurones (td-tomato/Agrp-Cre) or Rip-Cre neurones (td-tomato/Rip-Cre) were treated with prolactin and perfused 45 minutes later. Brains were processed for double-labelled immunohistochemistry for pSTAT5, a marker of prolactin-induced intracellular signalling, and td-tomato. In addition, Agrp-Cre mice and Rip-Cre mice were crossed with mice in which the prolactin receptor gene (Prlr) was flanked with LoxP sites (Prlrlox/lox mice). The Prlrlox/lox construct was designed such that Cre-mediated recombination resulted in deletion of the Prlr and expression of green fluorescent protein (GFP) in its place. In td-tomato/Rip-Cre mice, prolactin-induced pSTAT5 was co-localised with td-tomato, indicating that there is a subpopulation of Rip-Cre neurones in the arcuate nucleus that respond to prolactin. Furthermore, mice with a specific deletion of Prlr in Rip-Cre neurones had lower body weights, increased oxygen consumption, increased running wheel activity and numerous cells in the arcuate nucleus had positive GFP staining indicating deletion of Prlr from Rip-Cre neurones. By contrast, no co-localisation of td-tomato and pSTAT5 was observed in td-tomato/Agrp-Cre mice after prolactin treatment. Moreover, Prlrlox/lox /Agrp-Cre mice had no positive GFP staining in the arcuate nucleus and did not differ in body weight compared to littermate controls. Overall, these results indicate that Rip-Cre neurones in the arcuate nucleus are responsive to prolactin and may play a role in the orexigenic effects of prolactin, whereas prolactin does not directly affect Agrp neurones.

Assessing finasteride-associated sexual dysfunction using the FAERS database.

BACKGROUND: Postmarketing reports suggest that finasteride causes sexual dysfunction despite a low incidence reported in clinical trials. Therefore, the extent of risk remains unknown. OBJECTIVE: To determine whether the risk of sexual dysfunction is higher among individuals treated with finasteride compared to a baseline risk for all other drugs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: A case by non-case disproportionality approach was used whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. The National Ambulatory Medical Care Survey (NAMCS) was used to confirm results. RESULTS: A significant disproportionality in reporting of sexual dysfunction with the use of finasteride was observed whether finasteride was indicated for hair loss (ROR = 138.17, 95% CI: 133.13, 143.4), prostatic hyperplasia (ROR = 93.88, 95% CI: 84.62, 104.16) or any indication (ROR = 173.18, 95% CI: 171.08, 175.31). When these results were stratified by age, disproportionality was strongest at 31-45 years. CONCLUSION: Use of finasteride has led to an increase in reports of sexual dysfunction where it is believed to be the primary suspect.

Conjugal amyotrophic lateral sclerosis: a case report from Scotland.

BACKGROUND: Conjugal amyotrophic lateral sclerosis is rare, with significant effects on psychological and care needs. We report a case of conjugal amyotrophic lateral sclerosis disease from central Scotland. This case is particularly unusual as both patients were diagnosed within an 18-month period and experienced the disease simultaneously, with similar symptomatology and progression. CASE PRESENTATION: Patient A was a 71-year-old man who presented with unilateral arm weakness and wasting. Patient B was a 68-year-old woman who presented with unilateral shoulder and elbow weakness. Diagnosis of amyotrophic lateral sclerosis was made within a few months of presentation in both cases, based on typical clinical symptomatology together with supportive neurophysiological testing. Interventions included enteral feeding and non-invasive ventilation. The time period between symptom onset and death was 5 years for Patient A and 3.5 years for Patient B. CONCLUSION: This case illustrates two main points: the care issues surrounding cases of conjugal neurological disease, and the psychological issues in these patients. There are significant care issues arising when co-habiting couples both develop severe functionally limiting neurological diseases at the same time. The more slowly progressive nature of Patient A's disease may be at least partially explained by the support he was able to receive from Patient B before she developed symptoms. Secondly, there are important psychological effects of living with someone with the same - but more advanced - progressive and incurable neurological disease. Thus, Patient B was reluctant to have certain interventions that she had observed being given to her husband. Lastly, no plausible shared environmental risk factors were identified, implying that the co-occurrence of ALS in this couple was a random association.

Disappearance of the hyperdense MCA sign after stroke thrombolysis: implications for prognosis and early patient selection for clot retrieval.

Disappearance of the hyperdense middle cerebral artery sign (HMCAS) following intravenous thrombolysis for ischaemic stroke is associated with improved outcome. Debate exists over which radiological thrombus characteristics can predict disappearance of the HMCAS after thrombolysis such as vessel attenuation or extent of thrombus length. Methods Ischaemic stroke patients treated with intravenous thrombolysis from our hospital were entered into a European registry. Patient demographics, stroke severity pre- and 24 hours post-thrombolysis were recorded. Patients with HMCAS were identified from the registry using records from 2010-2013. Images from the pre and post-thrombolysis computed tomography scan were measured. Thrombus characteristics (length and attenuation), extent of ischaemic change and clinical outcome (stroke severity and 3 month survival) were compared between patients with and without HMCAS disappearance. Logistic regression analysis was performed to identify predictors of HMCAS disappearance. Results HMCAS was present in 88/315 (28%) of thrombolysed ischaemic stroke patients. 36/88 (41%) of patients had thrombus disappearance 24 hours after thrombolysis. HMCAS disappearance was associated with reduced stroke severity, less radiological ischaemic change, and higher 3 month survival (87% vs 56%). Median thrombus length was shorter in the HMCAS disappearance group (11 vs 17 mm, p = 0.0004), but no significant difference in vessel attenuation was observed (48 vs 51 Hounsfield Units, p = 0.25). HMCAS disappearance occurred in 73% of cases where HMCAS length was > 10 mm, 38% when length was 10-20 mm, and 21% if < 20 mm. Thrombus length was the only independent predictor of HMCAS disappearance (odds ratio 0.90 per mm; 95% CI 0.84-0.96, p = 0.01). Conclusion Disappearance of HMCAS is associated with better clinical and radiological outcomes. A shorter thrombus is more likely to disappear postthrombolysis. The data highlight the limitation of intravenous thrombolysis in patients with longer hyperattenuated vessels, and the potential role for clot retrieval in such patients.

Protocol for meta-analysis of temperature reduction in animal models of cardiac arrest.

Targeted temperature management (TTM) of 32-34 °C has been the standard treatment for out-of-hospital cardiac arrest since clinical trials in 2002 showed benefits to survival and neurological outcome. Recently, this treatment has been challenged by another clinical trial showing no difference in outcome between TTM of 33 °C and 36 °C. This protocol describes the methodology for a meta-analysis detailing temperature-reducing interventions to treat global ischaemia in animal models. By combining relevant data sets in the literature, we will explore the experimental evidence for TTM. Our aims are to explain possible translational gaps and provide methodological considerations for future experimental research and clinical trials.