Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Blood Oxygen Depletion Is Independent of Dive Function in a Deep Diving Vertebrate, the Northern Elephant Seal

Although energetics is fundamental to animal ecology, traditional methods of determining metabolic rate are neither direct nor instantaneous. Recently, continuous blood oxygen (O(2)) measurements were used to assess energy expenditure in diving elephant seals (Mirounga angustirostris), demonstrating that an exceptional hypoxemic tolerance and exquisite management of blood O(2) stores underlie the extraordinary diving capability of this consummate diver. As the detailed relationship of energy expenditure and dive behavior remains unknown, we integrated behavior, ecology, and physiology to characterize the costs of different types of dives of elephant seals. Elephant seal dive profiles were analyzed and O(2) utilization was classified according to dive type (overall function of dive: transit, foraging, food processing/rest). This is the first account linking behavior at this level with in vivo blood O(2) measurements in an animal freely diving at sea, allowing us to assess patterns of O(2) utilization and energy expenditure between various behaviors and activities in an animal in the wild. In routine dives of elephant seals, the blood O(2) store was significantly depleted to a similar range irrespective of dive function, suggesting that all dive types have equal costs in terms of blood O(2) depletion. Here, we present the first physiological evidence that all dive types have similarly high blood O(2) demands, supporting an energy balance strategy achieved by devoting one major task to a given dive, thereby separating dive functions into distinct dive types. This strategy may optimize O(2) store utilization and recovery, consequently maximizing time underwater and allowing these animals to take full advantage of their underwater resources. This approach may be important to optimizing energy expenditure throughout a dive bout or at-sea foraging trip and is well suited to the lifestyle of an elephant seal, which spends > 90% of its time at sea submerged making diving its most “natural” state

WR-2721 (Amifostine) Ameliorates Cisplatin-Induced Hearing Loss But Causes Neurotoxicity In Hamsters: Dose-Dependent Effects

Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR (n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone (n = 5) or were untreated (n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatin’s ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABR’s interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed

The discordance between evidence and health policy in the United States: the science of translational research and the critical role of diverse stakeholders

Abstract Background There is often a discordance between health research evidence and public health policies implemented by the United States federal government. In the process of developing health policy, discordance can arise through subjective and objective factors that are unrelated to the value of the evidence itself, and can inhibit the use of research evidence. We explore two common types of discordance through four illustrative examples and then propose a potential means of addressing discordance. Discussion In Discordance 1, public health authorities make recommendations for policy action, yet these are not based on high quality, rigorously synthesised research evidence. In Discordance 2, evidence-based public health recommendations are ignored or discounted in developing United States federal government policy. Both types could lead to serious risks of public health and clinical patient harms. We suggest that, to mitigate risks associated with these discordances, public health practitioners, health policy-makers, health advocates and other key stakeholders should take the opportunity to learn or expand their knowledge regarding current research methods, as well as improve their skills for appropriately considering the strengths and limitations of research evidence. This could help stakeholders to adopt a more nuanced approach to developing health policy. Stakeholders should also have a more insightful contextual awareness of these discordances and understand their potential harms. In Discordance 1, public health organisations and authorities need to acknowledge their own historical roles in making public health recommendations with insufficient evidence for improving health outcomes. In Discordance 2, policy-makers should recognise the larger impact of their decision-making based on minimal or flawed evidence, including the potential for poor health outcomes at population level and the waste of huge sums. In both types of discordance, stakeholders need to consider the impact of their own unconscious biases in championing evidence that may not be valid or conclusive. Conclusion Public health policy needs to provide evidence-based solutions to public health problems, but this is not always done. We discuss some of the factors inhibiting evidence-based decision-making in United States federal government public health policy and suggest ways these could be addressed