The UK psychiatrists' experience of rationalising antipsychotics in adults with intellectual disabilities: A qualitative data analysis of free-text questionnaire responses.

BACKGROUND: Overprescribing of off-licence psychotropic medications, particularly antipsychotics, for challenging behaviours in people with intellectual disabilities without a psychiatric disorder is a significant public health concern. In the United Kingdom, the National Health Service England launched an initiative in 2016, 'STopping Over-Medication of People with learning disabilities, autism or both (STOMP)', to address this concern. STOMP is supposed to encourage psychiatrists in the United Kingdom and elsewhere to rationalise psychotropic medication use in people with intellectual disabilities. The current study aims to gather UK psychiatrists' views and experience of implementing the STOMP initiative. METHODS: An online questionnaire was sent to all UK psychiatrists working in the field of intellectual disabilities (estimated 225). Two open-ended questions allowed participants to write comments in response to these questions in the free text boxes. One question asked about the challenges psychiatrists faced locally to implement STOMP, and the other asked for examples of successes and positive experiences from the process. The free text data were analysed using a qualitative method with the help of the NVivo 12 plus software. RESULTS: Eighty-eight (estimated 39%) psychiatrists returned the completed questionnaire. The qualitative analysis of free-text data has shown variation within services in the experience and views of the psychiatrists. In areas with good support for STOMP implementation provided through adequate resources, psychiatrists reported satisfaction in the process with successful antipsychotic rationalisation, better local multi-disciplinary and multi-agency working, and increased awareness of STOMP issues among the stakeholders such as people with intellectual disabilities and their caregivers and multidisciplinary teams, and improved quality of life caused by reduced medication-related adverse events in people with intellectual disabilities. However, where resource utilisation is not optimum, psychiatrists seemed dissatisfied with the process with little success in medication rationalisation. CONCLUSIONS: Whereas some psychiatrists are successful and enthusiastic about rationalising antipsychotics, others still face barriers and challenges. Much work is needed to achieve a uniformly positive outcome throughout the United Kingdom.

O-GlcNAc transferase is required to maintain satellite cell function.

O-GlcNAcylation is a posttranslational modification considered to be a nutrient sensor that reports nutrient scarcity or surplus. Although O-GlcNAcylation exists in a wide range of cells and/or tissues, its functional role in muscle satellite cells (SCs) remains largely unknown. Using a genetic approach, we ablated O-GlcNAc transferase (OGT), and thus O-GlcNAcylation, in SCs. We first evaluated SC function in vivo using a muscle injury model and found that OGT deficient SCs had compromised capacity to repair muscle after an acute injury compared with the wild-type SCs. By tracing SC cycling rates in vivo using the doxycycline-inducible H2B-GFP mouse model, we found that SCs lacking OGT cycled at lower rates and reduced in abundance with time. Additionally, the self-renewal ability of OGT-deficient SCs after injury was decreased compared to that of the wild-type SCs. Moreover, in vivo, in vitro, and ex vivo proliferation assays revealed that SCs lacking OGT were incapable of expanding compared with their wild-type counterparts, a phenotype that may be explained, at least in part, by an HCF1-mediated arrest in the cell cycle. Taken together, our findings suggest that O-GlcNAcylation plays a critical role in the maintenance of SC health and function in normal and injured skeletal muscle.

Tight gene co-expression in BCB positive cattle oocytes and their surrounding cumulus cells.

BACKGROUND: Cytoplasmic and nuclear maturation of oocytes, as well as interaction with the surrounding cumulus cells, are important features relevant to the acquisition of developmental competence. METHODS: Here, we utilized Brilliant cresyl blue (BCB) to distinguish cattle oocytes with low activity of the enzyme Glucose-6-Phosphate Dehydrogenase, and thus separated fully grown (BCB positive) oocytes from those in the growing phase (BCB negative). We then analyzed the developmental potential of these oocytes, mitochondrial DNA (mtDNA) copy number in single oocytes, and investigated the transcriptome of single oocytes and their surrounding cumulus cells of BCB positive versus BCB negative oocytes. RESULTS: The BCB positive oocytes were twice as likely to produce a blastocyst in vitro compared to BCB- oocytes (P < 0.01). We determined that BCB negative oocytes have 1.3-fold more mtDNA copies than BCB positive oocytes (P = 0.004). There was no differential transcript abundance of genes expressed in oocytes, however, 172 genes were identified in cumulus cells with differential transcript abundance (FDR < 0.05) based on the BCB staining of their oocyte. Co-expression analysis between oocytes and their surrounding cumulus cells revealed a subset of genes whose co-expression in BCB positive oocytes (n = 75) and their surrounding cumulus cells (n = 108) compose a unique profile of the cumulus-oocyte complex. CONCLUSIONS: If oocytes transition from BCB negative to BCB positive, there is a greater likelihood of producing a blastocyst, and a reduction of mtDNA copies, but there is no systematic variation of transcript abundance. Cumulus cells present changes in transcript abundance, which reflects in a dynamic co-expression between the oocyte and cumulus cells.

Metabolomic signature of genetic potential for muscularity in beef cattle.

The aim of this study was to investigate the serum and meat metabolomic changes according to the genetic potential for muscularity of non-castrated Nellore males and its association with phenotypic traits. Forty-eight non-castrated Nellore males were separated into two groups based on their genetic potential for post-weaning muscularity: high (HM) and low (LM). Selection for muscularity did not cause noticeable differences in the traits evaluated during the finishing phase and after slaughter. However, several metabolites in meat and serum, have changed according to the muscularity group. HM animals presented an over-abundance of glycerol, glutamine, choline, methylhistidine, betaine, creatinine and methionine in serum, compared with their LM counterparts. Similarly, the meat samples of HM animals were rich in glucose-6-phosphate, lactate, pyruvate, creatinine, betaine, choline, glycerol and arginine relative to LM bulls. Inosine monophosphate was the only metabolite over-abundant in LM animals. In conclusion, the genetic potential for post-weaning muscularity did not affect performance during the finishing phase, carcass traits and meat quality. However, multivariate analysis shows that the genetic potential of muscularity can be correlated with serum lipid and protein metabolites, and with energy metabolism in meat, providing a footprint of cattle muscularity metabolism.

Quantitative Proteomics and Phosphoproteomics Analysis Revealed Different Regulatory Mechanisms of Halothane and Rendement Napole Genes in Porcine Muscle Metabolism.

Pigs with the Halothane (HAL) or Rendement Napole (RN) gene mutations demonstrate abnormal muscle energy metabolism patterns and produce meat with poor quality, classified as pale, soft, and exudative (PSE) meat, but it is not well understood how HAL and RN mutations regulate glucose and energy metabolism in porcine muscle. To investigate the potential signaling pathways and phosphorylation events related to these mutations, muscle samples were collected from four genotypes of pigs, wild type, RN, HAL, and RN-HAL double mutations, and subjected to quantitative proteomic and phosphoproteomic analysis using the TiO2 enrichment strategy. The study led to the identification of 932 proteins from the nonmodified peptide fractions and 1885 phosphoproteins with 9619 phosphorylation sites from the enriched fractions. Among them, 128 proteins at total protein level and 323 phosphosites from 91 phosphoproteins were significantly regulated in mutant genotypes. The quantitative analysis revealed that the RN mutation mainly affected the protein expression abundance in muscle. Specifically, high expression was observed for proteins related to mitochondrial respiratory chain and energy metabolism, thereby enhancing the muscle oxidative capacity. The high content of UDP-glucose pyrophosphorylase 2 (UGP2) in RN mutant animals may contribute to high glycogen storage. However, the HAL mutation mainly contributes to the up-regulation of phosphorylation in proteins related to calcium signaling, muscle contraction, glycogen, glucose, and energy metabolism, and cellular stress. The increased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CAMK2) in HAL mutation may act as a key regulator in these processes of muscle. Our findings indicate the different regulatory mechanisms of RN and HAL mutations in relation to porcine muscle energy metabolism and meat quality.

Human pancreas development.

A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting ß-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

Operative and 1-Year Outcomes of the Custom-Made Fenestrated Anaconda Aortic Stent Graft-A UK Multicenter Study.

BACKGROUND: Early and 1-year outcomes are presented for fenestrated endovascular aneurysm repair (FEVAR) of complex aortic aneurysmal disease with the custom-made Anaconda fenestrated stent graft in 101 patients. METHODS: Retrospective site-reported data from the first 101 elective cases (2010-2014) from 4 UK centers were studied to evaluate patient demographics, aneurysm morphology, clinical success, and 1-year outcomes in patients undergoing fenestrated aneurysm repair with the custom-made Anaconda device. RESULTS: 101 fenestrated grafts (median age 76, 85% male) were implanted with a total of 255 fenestrations (196 renal arteries, 48 superior mesenteric artery, and 11 celiac arteries) with 3% mortality, 98.4% target vessel patency (TVP) at 30 day follow-up. Although 15 type I or III endoleaks were demonstrated at completion angiography, all 10 type Ia endoleaks resolved spontaneously. Survival by Kaplan-Meier analysis was 97% and 91% at 1 month and 1 year, respectively; with 75.8% showing reduction in abdominal aortic aneurysm diameter and only 1 patient with sac expansion. Freedom from loss of TVP was 97.6%. CONCLUSIONS: Custom-made fenestrated Anaconda devices demonstrate low procedural mortality and a high rate of technical and clinical success at 30 days and 1 year.

Injury and illness in aquatic sport: how high is the risk? A comparison of results from three FINA World Championships.

BACKGROUND: Epidemiological information on injury/illness is required to develop effective injury prevention strategies. AIM: To assess the frequency and characteristics of injuries/illnesses (1) in the 4 weeks prior to and (2) during the Fédération Internationale de Natation (FINA) World Championships 2015 compared with 2013 and 2009. METHOD: (1) Athletes answered a retrospective questionnaire, and (2) the medical staff reported injuries/illnesses prospectively during the championships. RESULTS: (1) A quarter of responding athletes reported symptoms in the 4 weeks prior to the championships. More than half of all affected athletes presented with substantial severity, 80% took medication, 70% had overuse injuries and 30% did not modify their training regime despite symptoms. At the start of the championships, 70% of affected participants were still symptomatic. (2) During the championships, injury and illness incidence was 12.9 per 100 athletes. The most common injuries were shoulder sprains (5.7%) and muscle cramps of the lower back (5.7%). The most common illnesses were infections of the respiratory (33.9%) and gastrointestinal tract (23.5%). Risk factors included discipline and age, but not gender. Incidence was highest in athletes competing in high diving (HD), water polo (WP) and diving (DIV) for injuries, and WP and swimming (SW) for illnesses. The significantly higher incidence of injuries and illnesses at the FINA World Championships 2015 compared with 2013 and 2009 was most probably due to a similarly improved response rate of the medical staff. CONCLUSIONS: In aquatic sports, surveillance and health promotion should focus on prevention of out-of-competition overuse injuries and athlete education.

Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency.

OBJECTIVE: To review the doping status of dehydroepiandrosterone (DHEA) for female athletes with adrenal insufficiency within the framework of Therapeutic Use Exemption (TUE) applications for this proandrogen, which is included on the World Anti-Doping Agency (WADA)'s Prohibited List. DATA SOURCES AND MAIN RESULTS: Current knowledge of adrenal pathophysiology with a focus on the physiological role and pharmacological effects of DHEA in female athletes including placebo-controlled clinical trials of DHEA and consensus clinical practice and prescribing guidelines. CONCLUSIONS: Because there is no convincing clinical evidence to support the use of DHEA replacement therapy in women with adrenal failure, a TUE for DHEA is not justified by definite health benefit for either secondary or primary adrenal failure. This is consistent with the 2014 update of the US Endocrine Society guidelines, meta-analyses of DHEA treatment in women with or without adrenal failure, current WADA TUE guidance document for adrenal insufficiency and recent case law of WADA's Court of Arbitration for Sport.

Heterogeneous activation of a slow myosin gene in proliferating myoblasts and differentiated single myofibers.

Each skeletal muscle contains a fixed ratio of fast and slow myofibers that are distributed in a stereotyped pattern to achieve a specific motor function. How myofibers are specified during development and regeneration is poorly understood. Here we address this question using transgenic reporter mice that indelibly mark the myofiber lineages based on activation of fast or slow myosin. Lineage tracing indicates that during development all muscles have activated the fast myosin gene Myl1, but not the slow myosin gene Myh7, which is activated in all slow but a subset of fast myofibers. Similarly, most nascent myofibers do not activate Myh7 during fast muscle regeneration, but the ratio and pattern of fast and slow myofibers are restored at the completion of regeneration. At the single myofiber level, most mature fast myofibers are heterogeneous in nuclear composition, manifested by mosaic activation of Myh7. Strikingly, Myh7 is activated in a subpopulation of proliferating myoblasts that co-express the myogenic progenitor marker Pax7. When induced to differentiate, the Myh7-activated myoblasts differentiate more readily than the non-activated myoblasts, and have a higher tendency, but not restricted, to become slow myotubes. Together, our data reveal significant nuclear heterogeneity within a single myofiber, and challenge the conventional view that myosin genes are only expressed after myogenic differentiation. These results provide novel insights into the regulation of muscle fiber type specification.

Australasian College of Sports Physicians-position statement: the place of mesenchymal stem/stromal cell therapies in sport and exercise medicine.

PURPOSE AND SCOPE: This Position Statement has been written expressly for members of the Australasian College of Sports Physicians (ACSP); however, it may also be of interest to the wider medical community, sporting organisations, athletes and the general community. It has been informed by a comprehensive review of the scientific literature and the opinions of kindred organisations. This statement outlines the use of mesenchymal stem cell (MSC) therapies in the broad context of Sport and Exercise Medicine, recognising that every medical practitioner should respect: (1) the evidence for the therapeutic use of MSCs and (2) the priority for patient health and welfare.

Competing with injuries: injuries prior to and during the 15th FINA World Championships 2013 (aquatics).

BACKGROUND: Injury and illness surveillance is the foundation for the development of prevention strategies. OBJECTIVE: To examine injuries among the aquatic disciplines in the 4 weeks prior to and during the 2013 FINA World Championships. METHODS: The study was comprised of two components: (1) a retrospective athlete survey recording injuries in the 4 weeks prior to the Championships and (2) a prospective recording of injuries and illnesses by the medical teams of the participating countries and the local host medical team. RESULTS: One-third of the 1116 responding athletes reported an injury/physical complaint in the 4 weeks prior to the Championships. Significantly more women (36.7%) than men (28.6%) reported injuries. Divers reported the highest rate of injury/physical complaints (55.7%). At the start of the Championships, 70% of injured respondents (n=258) were still symptomatic; however, full participation was expected by 76%. During the Championships, 186 new injuries were reported (8.3/100 registered athletes) with the highest injury incidence rate in water polo (15.3/100 registered athletes). The most common injured body part was the shoulder (21%). A total of 199 illnesses were reported during the Championships (9.0/100 registered athletes) with the most common diagnosis of illness being gastrointestinal infection. Environmental exposure (allergy, otitis and jellyfish stings) was responsible for 27% of all illnesses in open water swimming. CONCLUSIONS: Injuries pose a significant health risk for elite aquatic athletes. A prospective study would improve understanding of out-of-competition injuries. Future injury and illness surveillance at FINA World Championships is required to direct and measure the impact of prevention strategies.

Nutrition considerations for open-water swimming.

Open-water swimming (OWS) is a rapidly developing discipline. Events of 5-25 km are featured at FINA World Championships, and the international circuit includes races of 5-88 km. The Olympic OWS event, introduced in 2008, is contested over 10 km. Differing venues present changing environmental conditions, including water and ambient temperatures, humidity, solar radiation, and unpredictable tides. Furthermore, the duration of most OWS events (1-6 hr) creates unique physiological challenges to thermoregulation, hydration status, and muscle fuel stores. Current nutrition recommendations for open-water training and competition are either an extension of recommendations from pool swimming or are extrapolated from other athletic populations with similar physiological requirements. Competition nutrition should focus on optimizing prerace hydration and glycogen stores. Although swimmers should rely on self-supplied fuel and fluid sources for shorter events, for races of 10 km or greater, fluid and fuel replacement can occur from feeding pontoons when tactically appropriate. Over the longer races, feeding pontoons should be used to achieve desirable targets of up to 90 g/ hr of carbohydrates from multitransportable sources. Exposure to variable water and ambient temperatures will play a significant role in determining race nutrition strategies. For example, in extreme environments, thermoregulation may be assisted by manipulating the temperature of the ingested fluids. Swimmers are encouraged to work with nutrition experts to develop effective and efficient strategies that enhance performance through appropriate in-competition nutrition.

Analysis of phosphofructokinase-1 activity as affected by pH and ATP concentration.

A key player in energy metabolism is phosphofructokinase-1 (PFK1) whose activity and behavior strongly influence glycolysis and thus have implications in many areas. In this research, PFK1 assays were performed to convert F6P and ATP into F-1,6-P and ADP for varied pH and ATP concentrations. PFK1 activity was assessed by evaluating F-1,6-P generation velocity in two ways: (1) directly calculating the time slope from the first two or more datapoints of measured product concentration (the initial-velocity method), and (2) by fitting all the datapoints with a differential equation explicitly representing the effects of ATP and pH (the modeling method). Similar general trends of inhibition were shown by both methods, but the former gives only a qualitative picture while the modeling method yields the degree of inhibition because the model can separate the two simultaneous roles of ATP as both a substrate of reaction and an inhibitor of PFK1. Analysis based on the model suggests that the ATP affinity is much greater to the PFK1 catalytic site than to the inhibitory site, but the inhibited ATP-PFK1-ATP complex is much slower than the uninhibited PFK1-ATP complex in product generation, leading to reduced overall reaction velocity when ATP concentration increases. The initial-velocity method is simple and useful for general observation of enzyme activity while the modeling method has advantages in quantifying the inhibition effects and providing insights into the process.

Effects of liquid-based diets with breweries grains enriched with isolated starch and fish oil on veal quality.

Since veal production has declined in the U.S., American veal producers are currently making efforts to implement new production standards to improve product quality and animal welfare. In this study, we hypothesized that diets containing brewery grains, starch and omega-3 fatty acids could lower a blood stress indicator and improve meat quality, mostly from a nutritional value stand point. Holstein bull calves with approximately 94.67 ± 12.07 kg of body weight and two months old were randomly assigned to 1 of 3 dietary treatments. Diets were formulated with nonmedicated milk replacer, microbreweries spent grains, and a mineral mix (CONTROL); CONTROL + isolated maize starch (STARCH); and CONTROL +3% fish oil (OMEGA-3). Veal calves fed all three diets were heavier than calves of the same age from experiments reported in the existing literature. Dietary treatments did not affect carcass weights, pH, color, moisture, sensory attributes, volatile profile, and fat quality indexes. Calves fed STARCH and OMEGA-3 showed the lowest levels of blood cortisol. Veal fed CONTROL and OMEGA-3 had higher concentrations of ΣMUFA when compared with STARCH. Veal fed OMEGA-3 had the highest concentrations of EPA, DHA, and Σn-3. Veal from all treatments had very high concentrations of ΣMUFA, mostly driven by high levels of c-9 18:1 n-9 from the milk replacer. Feeding OMEGA-3 lowered blood cortisol and increased levels of EPA and DHA without harming sensory attributes. Overall, including brewery grains, starch and fish oil in liquid diets containing milk replacer can improve veal production.

Non-Alcoholic Fatty Liver Disease Induced by Feeding Medium-Chain Fatty Acids Upregulates Cholesterol and Lipid Homeostatic Genes in Skeletal Muscle of Neonatal Pigs.

Non-alcoholic fatty liver disease (NAFLD) is a range of disorders characterized by lipid accumulation in hepatocytes. Although this spectrum of disorders is associated with adult obesity, recent evidence suggests that this condition could also occur independently of obesity, even in children. Previously, we reported that pigs fed a formula containing medium-chain fatty acids (MCFAs) developed hepatic steatosis and weighed less than those fed an isocaloric formula containing long-chain fatty acids (LCFAs). Our objective was to determine the association between NAFLD and the skeletal muscle transcriptome in response to energy and lipid intake. Neonatal pigs were fed one of three formulas: a control formula (CONT, n = 6) or one of two isocaloric high-energy formulas containing either long (LCFA, n = 6) or medium (MCFA, n = 6) chain fatty acids. Pigs were fed for 22 d, and tissues were collected. Body weight at 20 and 22 d was greater for LCFA-fed pigs than their CONT or MCFA counterparts (p < 0.005). Longissimus dorsi weight was greater for LCFA compared with MCFA, while CONT was intermediate (p < 0.05). Lean gain and protein deposition were greater for LCFA than for CONT and MCFA groups (p < 0.01). Transcriptomic analysis revealed 36 differentially expressed genes (DEGs) between MCFA and LCFA, 53 DEGs between MCFA and CONT, and 52 DEGs between LCFA and CONT (FDR < 0.2). Feeding formula high in MCFAs resulted in lower body and muscle weights. Transcriptomics data suggest that the reduction in growth was associated with a disruption in cholesterol metabolism in skeletal muscles.

Inhibition of pyruvate dehydrogenase accelerates anaerobic glycolysis under postmortem simulating conditions.

This research aimed to explore the potential influence of mitochondria on the rate of anaerobic glycolysis. We hypothesized that mitochondria could reduce the rate of anaerobic glycolysis and pH decline by metabolizing a portion of glycolytic pyruvate. We utilized an in vitro model and incorporated CPI-613 and Avidin to inhibit pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC), respectively. Four treatments were tested: 400 µM CPI-613, 1.5 U/ml Avidin, 400 µM CPI-613 + 1.5 U/ml Avidin, or control. Glycolytic metabolites and pH of the in vitro model were evaluated throughout a 1440-min incubation period. CPI-613-containing treatments, with or without Avidin, decreased pH levels and increased glycogen degradation and lactate accumulation compared to the control and Avidin treatments (P < 0.05), indicating increased glycolytic flux. In a different experiment, two treatments, 400 µM CPI-613 or control, were employed to track the fates of pyruvate using [13C6]glucose. CPI-613 reduced the contribution of glucose carbon to tricarboxylic acid cycle intermediates compared to control (P < 0.05). To test whether the acceleration of acidification in reactions containing CPI-613 was due to an increase in the activity of key enzymes of glycogenolysis and glycolysis, we evaluated the activities of glycogen phosphorylase, phosphofructokinase, and pyruvate kinase in the presence or absence of 400 µM CPI-613. The CPI-613 treatment did not elicit an alteration in the activity of these three enzymes. These findings indicate that inhibiting PDH increases the rate of anaerobic glycolysis and pH decline, suggesting that mitochondria are potential regulators of postmortem metabolism.

Determining muscle plasticity and meat quality development of low-input extended fed market-ready steers.

In March 2020, the World Health Organization declared COVID-19 a pandemic, which ultimately led to many meat processors temporarily shutting down or reducing processing capacity. This backlog in processing capacity forced many feedlots to retain cattle for longer periods of time and assume the risk of major market fluctuations. The aim of this study was to understand how a dietary insult affects meat quality and muscle metabolism in market-ready steers (590 kg). Sixteen market-ready (590 kg) commercial Angus crossbred steers were subjected to a maintenance diet of either forage or grain for 60 d. Longissimus lumborum (LL) muscle samples were collected immediately postmortem and processed for characteristics reflecting the underlying muscle fiber type and energy state of the tissue. Despite cattle being subjected to a 60-d feeding period, there were no detectable differences (P > 0.05) in carcass characteristics, color of lean, or ultimate pH (pHu). Moreover, our data show that muscle plasticity is rather resilient, as reflected by lack of significance (P > 0.05) in oxidative and glycolytic enzymes, myosin heavy chain isoforms (MyHC), myoglobin, and mitochondrial DNA (mtDNA) contents. These data show that market-ready steers are capable of withstanding a low-input feeding strategy up to 60 d without dramatically impacting underlying muscle characteristics and meat quality development.

Psychological mechanisms underlying doping attitudes in sport: motivation and moral disengagement.

We examined whether constructs outlined in self-determination theory (Deci & Ryan, 2002), namely, autonomy-supportive and controlling motivational climates and autonomous and controlled motivation, were related to attitudes toward performance-enhancing drugs (PEDs) in sport and drug-taking susceptibility. We also investigated moral disengagement as a potential mediator. We surveyed a sample of 224 competitive athletes (59% female; M age = 20.3 years; M = 10.2 years of experience participating in their sport), including 81 elite athletes. Using structural equation modeling analyses, our hypothesis proposing positive relationships with controlling climates, controlled motivation, and PEDs attitudes and susceptibility was largely supported, whereas our hypothesis proposing negative relationships among autonomous climate, autonomous motivation, and PEDs attitudes and susceptibility was not supported. Moral disengagement was a strong predictor of positive attitudes toward PEDs, which, in turn, was a strong predictor of PEDs susceptibility. These findings are discussed from both motivational and moral disengagement viewpoints.