Heat stress hinders growth and well-being in livestock, an effect that is perhaps exacerbated by the β1 agonist ractopamine. Heat stress deficits are mediated in part by reduced feed intake, but other mechanisms involved are less understood. Our objective was to determine the direct impact of heat stress on growth and well-being in ractopamine-supplemented feedlot lambs. Commercial wethers were fed under heat stress (40 °C) for 30 d, and controls (18 °C) were pair-fed. In a 2 × 2 factorial, lambs were also given a daily gavage of 0 or 60 mg ractopamine. Growth, metabolic, cardiovascular, and stress indicators were assessed throughout the study. At necropsy, 9th to 12th rib sections (four-rib), internal organs, and feet were assessed, and sartorius muscles were collected for ex vivo glucose metabolic studies. Heat stress increased (P < 0.05) rectal temperatures and respiration rates throughout the study and reduced (P < 0.05) weight gain and feed efficiency over the first week, ultrasonic loin-eye area and loin depth near the end of the study, and four-rib weight at necropsy. Fat content of the four-rib and loin were also reduced (P < 0.05) by heat stress. Ractopamine increased (P < 0.05) loin weight and fat content and partially moderated the impact of heat stress on rectal temperature and four-rib weight. Heat stress reduced (P < 0.05) spleen weight, increased (P < 0.05) adrenal and lung weights, and was associated with hoof wall overgrowth but not organ lesions. Ractopamine did not affect any measured indicators of well-being. Heat stress reduced (P < 0.05) blood urea nitrogen and increased (P < 0.05) circulating monocytes, granulocytes, and total white blood cells as well as epinephrine, TNFα, cholesterol, and triglycerides. Cortisol and insulin were not affected. Heat stress reduced (P < 0.05) blood pressure and heart rates in all lambs and increased (P < 0.05) left ventricular wall thickness in unsupplemented but not ractopamine-supplemented lambs. No cardiac arrhythmias were observed. Muscle glucose uptake did not differ among groups, but insulin-stimulated glucose oxidation was reduced (P < 0.05) in muscle from heat-stressed lambs. These findings demonstrate that heat stress impairs growth, metabolism, and well-being even when the impact of feed intake is eliminated by pair-feeding and that systemic inflammation and hypercatecholaminemia likely contribute to these deficits. Moreover, ractopamine improved muscle growth indicators without worsening the effects of heat stress.

The growing prevalence of antibiotic-resistant bacterial pathogens and the lack of new medicines to treat the infections they cause remain a significant global threat. In recent years, this ongoing unmet need has encouraged more research groups to focus on the discovery and development of nontraditional antibacterial agents, ranging from anti-virulence strategies to bacteriophage and ways to modulate the microbiome. The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is a global nonprofit public−private partnership dedicated to accelerating antibacterial-related research. Importantly, the CARB-X portfolio supports a wide variety of novel and innovative nontraditional programs to help the global antibacterial research ecosystem understand the potential that these modalities can play in the management or prevention of serious infections. We describe here the breadth of the CARB-X pipeline of novel nontraditional products.

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In the accounts which have been given [Dunn, McLetchie & Sheehan, 1943;Dunn, Kirkpatrick, McLetchie & Telfer, 1943] of the finding of necrosis of the pancreatic islets after intravenous injection of alloxan in rabbits, it was pointed out that this lesion came to light only because of the unexpected deaths at 12-48 hr. of certain of the animals so treated. Later it was recognized that such deaths were preceded by hypoglyeaemia and hypothermia, and sometimes by convulsions as had been observed by Jacobs [1937]. The doses which gave fatal results were usually relatively large, 200-300 mg./kg. body weight, but it was known, from experiments done prior to finding the islet lesions, that similar deaths might occur, though rarely, after a much smaller dose, in one case 25 mg./kg. On the other hand, somne rabbits had survived for more than 48 hr. doses of 300 and even 500 mg./kg., given on 1 day, without it being realized from ordinary observation that they had pfassed through a critical phase. As the pancreas was not examined in these animals the condition of the islets was not ascertained, nor was any alteration of the blood sugar suspected. Once the lesion of the islets had been found it appeared desirable that further information should be obtained as to the conditions of its occurrence and its pathogenesis, and it has been possible to carry out some experiments with this in view. These experiments have combined general observations on the animals and estimations of blood sugar with histological examination of the pancreas, and have been intended to find answers to three main questions: (1) the frequency of occurrence of islet necrosis after single intravenous doses of alloxan such as have been known to produce it; (2) the rate of development of necrosis from the earliest stages, and (3) the effects, if any, of smaller doses. EXPERIMENTSThe rabbits used were bf various breeds. They were kept in metabolism cages and their usual daily food was 150 g. each of oats and bran, mixed with 200 c.c. water. About 150 g. cabbage was also given daily with rare lapses due PH. CIII.

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