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Understanding the global economic importance of farmed animals to society is essential as a baseline for decision making about future food systems. We estimated the annual global economic (market) value of live animals and primary production outputs, e.g., meat, eggs, milk, from terrestrial and aquatic farmed animal systems. The results suggest that the total global market value of farmed animals ranges between 1.61 and 3.3 trillion USD (2018) and is expected to be similar in absolute terms to the market value of crop outputs (2.57 trillion USD). The cattle sector dominates the market value of farmed animals. The study highlights the need to consider other values of farmed animals to society, e.g., finance/insurance value and cultural value, in decisions about the sector's future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corresponding author and all co-authors report that financial support was provided by Bill and Melinda Gates Foundation. Corresponding author and all co-authors reports financial support was provided by Commonwealth and Development Office of UK government., (© 2023 The Authors.)

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

Introduction: Foot-and-mouth disease (FMD) is a highly contagious viral disease that is endemic in East Africa. FMD virus infection incurs significant control costs and reduces animal productivity through weight loss, lowered milk yield, and potentially death but how household's respond to these losses may differentially affect household income and food consumption., Methodology: To address this, we use unique data from a FMD outbreak to assess how household production and consumption activities change from before to during the outbreak. Data came from a 2018 survey of 254 households in selected Tanzanian wards and sub-counties in Uganda. The data includes household recall of before and during an outbreak in the past year on livestock and livestock product sales, milk and beef consumption, as well as related changes in market prices. We apply both difference-in-difference and change in difference ordinary least squares regressions with fixed effects to evaluate the impact of FMD on household production and consumption., Results and Discussion: We find that households reported the largest reductions in livestock and livestock product sales, followed by reduced milk consumption and animal market prices. The changes in household income from livestock sales appears to be driven by FMD virus infection within the household herd while changes in market prices of substitute protein sources are primary associated with changes in milk and beef consumption. The role of widespread market price effects across both infected and uninfected herds and countries, tends to suggest that stabilizing prices will likely have a large impact on household nutritional security and income generation. We also propose that promoting diversity in market activity may mitigate differing impacts on households in FMD endemic regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kerfua, Railey and Marsh.)

Background: Wide differences in health exist between places in the UK, underscored by economic inequalities. Preston, an economically disadvantaged city in England, implemented a new approach to economic development, known as the Community Wealth Building programme. Public and non-profit organisations modified their procurement policies to support the development of local supply chains, improve employment conditions, and increase socially productive use of wealth and assets. We aimed to investigate the effect of this programme on population mental health and wellbeing., Methods: Difference-in-differences techniques compared trends in mental health outcomes in Preston, relative to matched control areas before (2011-15) and after (2016-19) the introduction of the programme. Outcomes were antidepressant prescribing, prevalence of depression, and mental health related hospital attendance rates using data provided by National Health Service Digital, the Quality and Outcomes Framework, and the Office for National Statistics. Additional analysis compared local authority measures of life satisfaction, median wages, and employment with synthetic counterfactuals created using Bayesian Structural Time Series., Findings: The introduction of the Community Wealth Building programme was associated with reductions in the prescribing of antidepressants (1·3 average daily quantities per person [95% CI 0·72-1·78) and prevalence of depression (2·4 per 1000 population [0·42-4·46]), relative to the control areas. The local population also experienced a 9% improvement in life satisfaction (95% credible interval 0-19·6%) and 11% increase in median wages (1·8-18·9%), relative to expected trends. Associations with employment and mental health related hospital attendance outcomes did not reach statistical significance., Interpretation: During the period in which the Community Wealth Building programme was introduced, there were fewer mental health problems than would have been expected compared with other similar areas, as life satisfaction and economic measures improved. This approach potentially provides an effective model for economic regeneration potentially leading to substantial health benefits., Funding: National Institute for Health Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Standardized acute asthma management with score-based, respiratory therapist (RT)-driven pathways and protocols improves outcomes including decreased length of stay (LOS) and time on continuous albuterol therapy. Limited data are available for the safety of continuous albuterol used outside of pediatric ICU (PICU). We use a modified pediatric asthma score (PAS) for the asthma pathway at our institution. The safety and effectiveness of using PAS to initiate/stop continuous albuterol as part of a score-based, RT-driven asthma pathway were evaluated., Methods: A retrospective review of children ≥ 2 y admitted for asthma exacerbation to the PICU and step-down unit who received continuous albuterol as part of the asthma pathway during 2017-2019 was completed. Demographic and clinical data were extracted including PAS, dose and duration of continuous albuterol, LOS, and complications. Outcomes of subjects admitted to the PICU and step-down unit were compared., Results: Results are expressed as median (interquartile range). The study included 412 children (61% male, 59.9% Black, 92.7% non-Hispanic, 44.9% moderate persistent asthma) with age and weight of 6.4 (4.0-10.0) y and 24.8 (17.3-39.5) kg, respectively. Most children were admitted to step-down unit (71.1%). Initial albuterol dose, duration, and LOS were 15 (10-20) mg/h, 9.1 (5.7-16.0) h, and 1.4 (0.9-2.3) d, respectively. Respiratory support was required by 29% of subjects. Need to restart therapy (2.9%), transfer to PICU (1.7%), and intubation (0.5%) were infrequent. No pneumothoraces or deaths were reported. Emergency department visits (3.9%) or readmissions (0.7%) within 30 d of discharge were low. Subjects admitted to the PICU were sicker and required more therapies and respiratory support than those admitted to the step-down unit., Conclusions: Use of an RT-driven, score-based pathway for initiation and discontinuation of continuous albuterol for treatment of pediatric asthma exacerbation was safe and effective in the PICU and step-down unit., Competing Interests: Dr Berlinski discloses relationships with Cystic Fibrosis Foundation, Mylan, National Institutes of Health, Therapeutic Development Network, Trudell Medical International, Vertex, and the International Pharmaceutical Aerosol Consortium on Regulation and Science. Ms Willis is a section editor for Respiratory Care. The remaining authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

We present the case of a 71-year-old man who presented to the ear, nose and throat department with complete nasal obstruction and facial plethora on bending forward. Clinical examination was positive for Pemberton's sign. Computed tomography and ultrasonography demonstrated bilateral brachiocephalic vein thrombosis secondary to pacemaker insertion. This case highlights a novel complication of pacemaker insertion.

Many children consume more sugar than is recommended, and caregivers often find it difficult to change this habit once established. This thematic synthesis aims to identify the "critical situations" where caregivers may be more likely to offer infants sugary drinks and snacks. This thematic synthesis is reported in accordance with the statement for enhancing transparency in reporting the synthesis of qualitative research (ENTREQ). Our confidence in the findings of our synthesis was assessed using the CERQual (Confidence in the Evidence From Reviews of Qualitative Research Approach). We included 16 studies from the United States, the United Kingdom, Australia, and Denmark. We identified eight "critical situations" when caregivers may be more likely to offer sugary drinks and snacks to infants. Interventions that seek to reduce sugar intake for caries prevention in infants and young children may be more successful if they provide caregivers with practical parenting strategies to replace the nonnutritive functions of sugary foods and drinks, as opposed to taking an information-giving approach., (© The Author(s) 2016.)

Unlabelled: The extended trochanteric osteotomy (ETO) is widely used for revision total hip arthroplasty (THA). We describe a novel technique to reattach the extended trochanteric osteotomy using a suture cord. We retrospectively reviewed 20 patients who underwent revision by this technique with a minimum followup of 2 years (mean, 2.2 years; range, 2-4 years). Bony union of the osteotomy occurred in 19 patients and fibrous union in one patient who remained asymptomatic. We observed proximal migration of the osteotomy fragment in one patient (5 mm) who had bony union of the osteotomy. This technique of anchoring the osteotomy fragment directly onto the prosthetic stem using a suture cord provides a secure fixation and does not endanger the blood supply of the osteotomy. It also has the advantage of avoiding the morbidity associated with cerclage wires and the costs associated with cabling systems., Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

The authors describe an acyclovir-resistant varicella zoster virus infection in a pediatric patient after hematopoietic stem cell transplant, the use of foscarnet as salvage therapy, and review the literature to clarify the pediatric experience with foscarnet in this setting. A novel thymidine kinase mutation is described, along with a new phenotypic assay for characterizing acyclovir resistance in varicella zoster virus.

We report a case of pediatric pneumococcal endocarditis (PPE) and review the English language literature on this disease. Thirty-two cases of PPE were identified since 1900. One-fourth of these were reported since 1990. Clinical features differed from adult cases, with mitral valve involvement being more frequent and Osler's triad rarely present in children. Congenital heart disease was the only identifiable risk factor. Medical therapy alone resulted in a high mortality rate that was improved in the group of patients receiving combined medical and surgical interventions. PPE is a rare infection that has been reported more frequently in the era of increasing antibiotic resistance. Unlike typical "subacute" endocarditis caused by viridans streptococci, PPE is an aggressive disease with a high mortality rate. Early surgical intervention might improve survival.

Roxifiban (DMP 754) is a glycoprotein (GP) IIb/IIIa antagonist. Following oral administration to humans, roxifiban is metabolized to its primary active zwitterionic form, XV459, and several minor, active, hydrolyzed and hydroxylated metabolites, namely, M1a (DPC-AD3508), M1b (DPC-AD6128), M2 (SW156), M3 (DPC-AG2185), M8a (DPC-AF5814), and M8b (DPC-AF5818). Quantification of these metabolites in humans was not workable with a previous analytical method due to ion suppression of at least four of the analytes by a competitive displacer, DMP 728. This compound, which is another GP IIb/IIIa antagonist with very high affinity for the platelet receptor, was added to harvested blood samples in millimolar quantity to liberate XV459 from the GP IIb/IIIa receptor. An automated ion exchange solid phase extraction (IX-SPE) procedure was developed to selectively extract the seven metabolites of roxifiban and its deuterated internal standard while specifically excluding DMP 728. Among the six hydroxylation metabolites, there were two pairs of epimeric diastereomers (M1a/M1b and M8a/M8b) and one pair of geometric isomers (M2/M3), corresponding to three critical chromatographic pairs that needed to be base-line resolved because of the lack of specificity of MS/MS detection for these isomers. A new LC/MS/MS assay was developed to simultaneously quantify the seven metabolites in human plasma. The assay method was validated under GLP conditions over the concentration range of 0.5 to 80 nM for each of the analytes and successfully applied to assaying approximately 500 plasma samples from clinical trials., (Copyright 2003 Elsevier Science B.V.)

In this work, a high-throughput and high-performance bioanalytical system is described that is capable of extracting and analyzing 1152 plasma samples within 10 hours. A Zymark track robot system interfaced with a Tecan Genesis liquid handler was used for simultaneous solid-phase extraction of four 96-well plates in a fully automated fashion. The extracted plasma samples were injected onto four parallel monolithic columns for separation via a four-injector autosampler. The use of monolithic columns allowed for fast and well-resolved separations at a considerably higher flow rate without generating significant column backpressure. This resulted in a total chromatographic run cycle time of 2 min on each 4.6 x 100 mm column using gradient elution. The effluent from the four columns was directed to a triple quadrupole mass spectrometer equipped with an indexed four-probe electrospray ionization source (Micromass MUX interface). Hence, sample extraction, separation, and detection were all performed in a four-channel parallel format that resulted in an overall throughput of about 30 s per sample from plasma. The performance of this system was evaluated by extracting and by analyzing twelve 96-well plates (1152) of human plasma samples spiked with oxazepam at different concentrations. The relative standard deviation (RSD) of analyte sensitivity (slope of calibration curve) across the four channels and across the 12 plates was 5.2 and 6.8%, respectively. An average extraction recovery of 77.6% with a RSD of 7.7% and an average matrix effect of 0.95 with a RSD of 5.2% were achieved using these generic extraction and separation conditions. The good separation efficiency provided by this system allowed for rapid method development of an assay quantifying the drug candidate and its close structural analog metabolite. The method was cross-validated with a conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay., (Copyright 2002 John Wiley & Sons, Ltd.)

Salivary histatins are potent in vitro antifungal proteins and have promise as therapeutic agents against oral candidiasis. We performed pharmacological studies directed at understanding the biochemical basis of Hst 5 candidacidal activity. Three inhibitors of mitochondrial metabolism: carbonyl cyanide p-chlorophenylhydrazone, dinitrophenol, and azide inhibited Hst 5 killing of Candida albicans, while not inhibiting cellular ATP production. In contrast, Hst 5 caused a drastic reduction of C. albicans intracellular ATP content, which was a result of an efflux of ATP. Carbonyl cyanide p-chlorophenylhydrazone, dinitrophenol, and azide inhibited Hst 5-induced ATP efflux, thus establishing a correlation between ATP release and cell killing. Furthermore, C. albicans cells were respiring and had polarized membranes at least 80 min after ATP release, thus implying a non-lytic exit of cellular ATP in response to Hst 5. Based on evidence that transmembrane ATP efflux can occur in the absence of cytolysis through a channel-like pathway and that released ATP can act as a cytotoxic mediator by binding to membrane purinergic receptors, we evaluated whether extracellular ATP released by Hst 5 may have further functional role in cell killing. Consistent with this hypothesis, purinergic agonists BzATP and adenosine 5'O-(thiotriphosphate) induced loss of C. albicans cell viability and purinergic antagonists prevented Hst 5 killing.

The promoter for the rat follicle-stimulating hormone receptor (FSHR) gene contains a conserved consensus E box sequence and an initiator-like region (InR) sequence. Deletion analysis and transient transfections showed that a 114-base pair region (-143 to -30) that encompasses the E box and the InR was sufficient for greater than 75% of promoter function. DNase I footprint analysis showed that the E box and InR were protected by nuclear proteins from rat Sertoli cells, and the E box region was shown by electrophoretic mobility shift assays (EMSA) to be a site of Sertoli protein interactions. Mutations in the E box disrupted these interactions and reduced FSHR promoter activity. Co-transfection of the inhibitor of DNA binding (Id) with an FSHR/luciferase construct into mouse Sertoli 1 cells reduced FSHR promoter activity. Using EMSA, the upstream stimulatory factor was shown to be a component of the complexes that interacted with the E box in the FSHR promoter. Binding of proteins from rat Sertoli cells to the InR was demonstrated using EMSA. Also, an oligonucleotide that represented the sequence of the terminal deoxynucleotidyltransferase InR displaced the complexes at the FSHR InR. Mutations in the InR resulted in a significant reduction of FSHR promoter activity.

A method of analysis for the determination of alosetron in human plasma or serum has been developed. The method was fully automated using a laboratory robot in order to improve analytical precision, efficiency and safety. The assay involved solid-phase extraction with reversed-phase HPLC separation and fluorescence detection. A validation exercise over the concentration range of 0.1 to 20 ng/ml demonstrated the selectivity, linearity, sensitivity, accuracy, precision, extraction efficiency, ruggedness and stability of the method. The method has been applied in support of numerous human pharmacokinetic/biopharmaceutic studies over the last five years.

We sought to develop an assay for measuring the inhibition of P-glycoprotein (Pgp) function in whole blood as an indicator of in vivo drug activity. Since the CD56(+) subset of peripheral blood lymphocytes (PBLs) has been shown to express functional Pgp, the changes in rhodamine 123 (R123) uptake by CD56(+) PBLs from GG918-treated and untreated whole blood were used as the basis for these studies. In an ex vivo study, heparin-treated whole blood was obtained from normal volunteers, and GG918 and R123 were added at various concentrations for time course analyses of dye loading. GG918 concentrations from 2.5 to 800 nm were tested in incubations ranging from 15 min to 3 h prior to R123 addition. R123 loading times ranged from 0 to 80 min. Flow cytometric analyses of the CD56(+) PBLs indicated that the resolution of Pgp inhibition was dependent on inhibitor concentration and time of R123 loading and independent of the R123 concentrations tested. In this ex vivo assay model, a dose-dependent response was seen for GG918 with a 2-fold increase in cellular R123 intensity being produced at a drug concentration of 80 nm. When this assay method was applied to blood samples from volunteers dosed p.o. with GG918, similar shifts in R123 fluorescence of the CD56(+) PBLs were observed with significant increases in R123 intensity occurring at serum concentrations as low as 40 nm. In contrast to assays in which target cell populations are enriched prior to testing, the addition of the substrate (R123) directly to the blood sample combined with the segregation of the target cells by specific immunofluorescence provides the investigator an indication of in situ activity of circulating drug. Thus, CD56(+) PBLs may prove useful as a surrogate target for monitoring multidrug resistance inhibitor activity in situ.

A fully automated HPLC procedure was developed for the analysis of a small volume of perfusion solutions from an isolated perfused rat kidney study. The method involved separation of (-)-2'-deoxy-3'-thiacytidine (3TC) from the matrix by dialysis with 10 mM potassium phosphate buffer pH 3.0. 3TC was subsequently separated from the dialysate as it flowed through a SCX cation-exchange cartridge. The trapped 3TC was then eluted with a mobile phase of 50 mM ammonium acetate buffer (pH 5.5)-methanol (90.5:9.5, v/v) at a flow-rate of 1.0 ml/min for 2 min. The eluent was directed to the HPLC system and chromatographed with a BDS C18 analytical column at a temperature of 45 degrees C. Detection of 3TC was carried out by UV absorption at 274 nm. The procedure was validated from 25 to 10,000 ng/ml. Coefficients of variance (C.V.) of 3TC quality control samples were less than 9%. C.V.s of the standard curve samples were also less than 10% except for the 25 ng/ml samples (11.5%). The mean interpolated concentrations were within 8% of the nominal concentrations for all samples. No interference from concurrent drugs was observed. Preliminary results suggested that this procedure may also be used for human serum and urine samples.

Ondansetron, an antagonist of the serotonin type 3 (5-HT3) receptor, is indicated for the treatment of chemotherapy-induced emesis. This study compares the pharmacokinetics, especially the bioavailability, of an ondansetron 8-mg solution when administered intravenously, orally, to the colon via nasogastric intubation, and to the rectum using a retention enema. Six healthy, male volunteers received ondansetron infused into the colon during the first treatment period. These subjects then received the remaining three treatments in random order, with a minimum 1-week washout period between treatments. Serial plasma samples were obtained for up to 24 hr after dosing in each treatment period. Absolute bioavailability after the oral dosing, colonic infusion, and rectal administration averaged 71 +/- 14, 74 +/- 26, and 58 +/- 18%, respectively. These values were not significantly different (P > 0.05). Values of Tmax and Cmax were also not significantly different among the nonparenteral routes. Mean absorption half-lives were 0.66, 1.1, and 0.75 hr after the oral, colonic, and rectal administrations, respectively. These results indicate that ondansetron is well absorbed in the intestinal segments studied including the upper small intestine, the colon, and the rectum and that sustained-release and suppository formulations of ondansetron are feasible.

A fully automated assay for the analysis of ranitidine in serum and plasma, with and without an internal standard, was validated. It utilizes robotic solid phase extraction with on-line high performance liquid chromatographic (HPLC) analysis. The ruggedness of the assay was demonstrated over a three-year period. A Zymark Py Technology II robotic system was used for serial processing from initial aspiration of samples from original collection containers, to final direct injection onto the on-line HPLC system. Automated serial processing with on-line analysis provided uniform sample history and increased productivity by freeing the chemist to analyse data and perform other tasks. The solid phase extraction efficiency was 94% throughout the assay range of 10-250 ng/mL. The coefficients of variation for within- and between-day quality control samples ranged from 1 to 6% and 1 to 5%, respectively. Mean accuracy for between-day standards and quality control results ranged from 97 to 102% of the respective theoretical concentrations.

The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly Branhamella) catarrhalis were significantly greater (P less than 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxime compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime.