If it’s not one thing, HIF’s another : immunoregulation by hypoxia inducible factors in disease

Hypoxia‐inducible factors (HIFs) have emerged in recent years as critical regulators of immunity. Localised, low oxygen tension is a hallmark of inflamed and infected tissues. Subsequent myeloid cell HIF stabilisation plays key roles in the innate immune response, alongside emerging oxygen‐independent roles. Manipulation of regulatory proteins of the HIF transcription factor family can profoundly influence inflammatory profiles, innate immune cell function and pathogen clearance and, as such, has been proposed as a therapeutic strategy against inflammatory diseases. The direction and mode of HIF manipulation as a therapy are dictated by the inflammatory properties of the disease in question, with innate immune cell HIF reduction being, in general, advantageous during chronic inflammatory conditions, while upregulation of HIF is beneficial during infections. The therapeutic potential of targeting myeloid HIFs, both genetically and pharmacologically, has been recently illuminated in vitro and in vivo , with an emerging range of inhibitory and activating strategies becoming available. This review focuses on cutting edge findings that uncover the roles of myeloid cell HIF signalling on immunoregulation in the contexts of inflammation and infection and explores future directions of potential therapeutic strategies

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Experimental Reduction of Hematocrit Affects Reproductive Performance in European Starlings, Sturnus Vulgaris

Given the function of hemoglobin and observed increases in hematocrit during periods of increased energetic demands, hematocrit and hemoglobin are assumed to be related to aerobic capacity. Reductions in hematocrit and hemoglobin during reproduction are similar in magnitude to increases associated with aerobically demanding activities and therefore we sought to investigate whether these reductions in hematology have consequences for reproductive performance. We analyzed associations between natural variation in hematology in free-living European starlings (Sturnus vulgaris) and reproductive performance. To test whether transient reductions in hematology during different stages of reproduction (egg production and late incubation/early chick rearing) affected measures of reproductive performance, we also manipulated hematology using phenylhydrazine (PHZ), which lyses red blood cells. To investigate effects of reductions of hematology during egg-laying, we treated females with PHZ or saline (control) upon completion of their unmanipulated first clutch and removed eggs to induce the production and rearing of a replacement clutch. To investigate effects of reductions of hematology during chick rearing, we treated females during incubation of the unmanipulated first clutch and then monitored the subsequent hatching and rearing of the clutch. Individuals with higher hematocrit and hemoglobin initiated nesting earlier.  Furthermore, higher hemoglobin levels during incubation were associated with a greater number of chicks fledged.  PHZ treatment prior to egg production resulted in a significant delay in the laying of replacement clutches, but had no effect on provisioning rate or the size or number of chicks fledged. PHZ treatment during incubation and early chick rearing resulted in decreased hatchling mass in all years and a decrease in the size and number of fledglings in one of two years. The year that the effect of PHZ was observed appeared to be a particularly difficult year, since hatchling mass, brood size at hatching and at fledging were low among control females compared to other years. Our results suggest that a reduction in hematology during reproduction can be functionally significant, but that these costs are context-dependent. &nbsp

Crescimento de regiões da carcaça de cordeiros abatidos com diferentes pesos Growth of carcass parts in slaughter lambs with different weights

O trabalho foi realizado no Setor de Ovinocultura do Departamento de Zootecnia da Universidade Federal de Santa Maria, objetivando determinar o crescimento das principais partes da carcaça e suas proporções em relação ao peso de corpo vazio e peso de carcaça fria de cordeiros abatidos com diferentes pesos. Foram utilizados 22 cordeiros machos inteiros, filhos de carneiros Texel e ovelhas cruzas (Texel x Ideal). Destes, quatro foram abatidos no início do experimento (24 horas após o nascimento), seis ao desmame (45 dias de idade) e os remanescentes aos 28 (6 animais) ou 33 kg (6 animais). Os cordeiros foram confinados em baias individuais, com suas respectivas mães, até o desmame. A determinação do crescimento dos cortes da carcaça foi realizada através de equações alométricas, utilizando-se o logaritmo do peso de cada região da carcaça, em função do logaritmo do PCF ou PCV. As proporções de quarto, paleta e pescoço, em relação ao PCV, foram semelhantes (P>0,05) nos pesos de abates estudados, no entanto, houve diferença (P<0,05) entre costela e espinhaço. Em relação ao PCF, houve diferença (P<0,05) entre os pesos de abate para as proporções de quarto, costela e pescoço. Os coeficientes de alometria encontrados demonstram que a costela é o corte de crescimento mais tardio, enquanto que as demais partes da carcaça são de crescimento precoce.<br>This work was performed at the Ovine Section of Animal Science Department, at Federal University of Santa Maria, Brazil. The purpose of this experiment was to determine the growth of the carcass cuts and percentages in relation to the empty body weight and cold carcass weight of lambs slaughtered at different weights. Twenty-two intact male lambs, sired by Texel males, from crossbreed Texel-Ideal dams were used. Four lambs were slaughtered at the beginning of the experiment (24 hours after birth) and three groups of six lambs were slaughtered at weaning and when reaching the weight of 28 and 33kg. The lambs were confined in individual stall together, with their respective mothers until weaning (45 days of age). To study the growth of the different cuts of the carcass, regression equation of the log. of the weight of each part, as a function of the log. of the empty body weight or cold carcass weight were fitted. The percentages of hindquarter, shoulder and neck in relation to the empty body weight were similar (P>0.05) in the weights studied, and of rib and backbone were different (P<0.05). In relation to the cold carcass weight the percentage of hindquarter, rib and neck showed difference (P<0.05). Among the cuts, the rib was late matured and the other cuts were early matured

An arginase 2 promoter transgenic illuminates immune cell polarisation in zebrafish

Innate immune responses to inflammation and infection are complex and represent major challenges for developing much needed new treatments for chronic inflammatory diseases and drug-resistant infections. To be ultimately successful, the immune response must be balanced to allow pathogen clearance without excess tissue damage, processes controlled by pro- and anti-inflammatory signals. The roles of anti-inflammatory signalling in raising an appropriate immune response are underappreciated, representing overlooked potential drug targets. This is especially true in neutrophils, a difficult cell type to study ex vivo owing to a short lifespan, dogmatically seen as being highly pro-inflammatory. Here, we have generated and describe the first zebrafish transgenic line [TgBAC(arg2:eGFP)sh571] that labels expression of the anti-inflammatory gene arginase 2 (arg2) and show that a subpopulation of neutrophils upregulate arginase soon after immune challenge with injury and infection. At wound-healing stages, arg2:GFP is expressed in subsets of neutrophils and macrophages, potentially representing anti-inflammatory, polarised immune cell populations. Our findings identify nuanced responses to immune challenge in vivo, responses that represent new opportunities for therapeutic interventions during inflammation and infection

Crescimento alométrico de osso, músculo e gordura em cortes da carcaça de cordeiros Texel segundo os métodos de alimentação e peso de abate Muscle, fat and bone allometric growth in Texel lambs carcasses cuts in relation to the feeding methods and slaughter weight

O experimento teve como objetivo estudar o crescimento alométrico dos diferentes tecidos do pescoço, costela, paleta e perna em relação ao peso do corte de cordeiros e cordeiras. Foram utilizados 22 machos inteiros e 23 fêmeas da raça Texel. Desses, sete foram abatidos no início do experimento e os demais, aos pesos de 25 ou 33kg. As ovelhas mais cordeiros foram distribuídos em três métodos de alimentação: M1 -Silagem de milho e concentrado, apenas aos cordeiros até o desmame, aos 60 dias; M2 - Silagem de milho e concentrado, apenas aos cordeiros até o desmame, aos 45 dias e M3 - Silagem de milho e concentrado para ovelha mais cordeiro até o desmame com 60 dias. Após o desmame, os cordeiros receberam silagem mais concentrado. Foi utilizado um delineamento inteiramente casualizado em arranjo fatorial 3 x 2 x 2 (3 métodos, 2 sexos e 2 pesos de abate). A determinação do crescimento foi obtida através da equação log y = log.a + b log.x, utilizando-se o logaritmo do peso de osso, músculo e gordura em função do logaritmo do peso do corte. Observou-se que o osso do pescoço e da costela foram precoce (b<1) em ambos os sexos, com coeficientes de alometria variando de 0,61 a 0,79; 0,81 a 0,88. O músculo foi isométrico (b=1) no pescoço e precoce (b<1) na costela com exceção dos machos do método um e três que apresentaram crescimento isométrico (b=1). A gordura foi tardia (b>1) independente de sexo e método de alimentação com coeficientes de alometria variando de 1,78 a 2,15 (pescoço) e 1,51 a 1,65 (costela). Na paleta, o osso foi precoce em ambos os sexos, com coeficientes de alometria variando de 0,76 a 0,79 e 0,54 a 0,58 respectivamente para machos e fêmeas. O músculo apresentou crescimento isométrico (b=1), independente de sexo e peso de abate. A gordura foi tardia (b>1) independente de peso de abate e sexo, com coeficientes de alometria variando de 1,80 a 2,12. Na perna o osso apresentou crescimento precoce nas fêmeas e isométricas nos machos, com coeficientes de alometria variando de 0,57 a 0,63 e 0,78 a 0,80 respectivamente para ambos os sexos O músculo apresentou crescimento isométrico (b=1), independente de sexo e peso de abate. A gordura foi tardia (b>1) independente de peso de abate e sexo com coeficientes de alometria variando de 1,80 a 2,12.<br>The experiment aimed at studying the allometric growth of the different tissues of neck, rib, shoulder blade and leg in relation to the cutting weight of male and female lambs. Twenty-two intact Texel males and 23 Texel females were used. Seven of them were slaughtered at the beginning of the experiment and the others at the weight of 25 or 33kg. Sheep and lambs were distributed into three methods of feeding: M1 - Corn silage and concentrate, only to lambs until weaning at 60 days old; M2 - Corn silage and concentrate, only to lambs until weaning at 45 days old and M3 - Corn silage and concentrate to ewe and lamb until weaning at 60 days old. After weaning, lambs were fed with silage plus concentrate. A completely randomized design outlined in a factorial arrangement 3 x 2 x 2 (3 methods, 2 sexes and 2 slaughter weights) was used. Determination of growth was obtained through the equation log y = log.a + b log.x, by using the logarithm of bone, muscle and fat weight in function of cutting weight logarithm. It was observed that neck and rib bone was precocious (b<1) in both sexes, with allometry coefficients varying from 0.61 to 0.79; 0.81 to 0.88. Muscle was isometric (b = 1) in neck and precocious (b<1) in rib, except for males of methods one and three, which presented isometric growth (b = 1). Fat was late (b>1), regardless of sex and feeding method with allometry coefficients varying from 1.78 to 2.15 (neck) and 1.51 to 1.65 (rib). In shoulder blade, bone was precocious in both sexes, with allometry coefficients varying from 0.76 to 0.79 and 0.54 to 0.58 for males and females, respectively. Muscle presented isometric growth (b = 1), regardless of sex and slaughter weight. Fat was late (b>1), regardless of slaughter weight and sex, with allometry coefficients varying from 1.80 to 2.12. In leg, bone growth was precocious in females and isometric in males, with allometry coefficients varying from 0.57 to 0.63 and 0.78 to 0.80, respectively, for both sexes. Muscle presented isometric growth (b = 1), regardless of sex and slaughter weight. Fat was late (b>1), regardless of slaughter weight and sex, with allometry coefficients varying from 1.80 to 2.12