Limitations of GPT-3.5 and GPT-4 in Applying Fleischner Society Guidelines to Incidental Lung Nodules.

Purpose: To evaluate the accuracy of GPT-3.5, GPT-4, and a fine-tuned GPT-3.5 model in applying Fleischner Society recommendations to lung nodules. Methods: We generated 10 lung nodule descriptions for each of the 12 nodule categories from the Fleischner Society guidelines, incorporating them into a single fictitious report (n = 120). GPT-3.5 and GPT-4 were prompted to make follow-up recommendations based on the reports. We then incorporated the full guidelines into the prompts and re-submitted them. Finally, we re-submitted the prompts to a fine-tuned GPT-3.5 model. Results were analyzed using binary accuracy analysis in R. Results: GPT-3.5 accuracy in applying Fleischner Society guidelines was 0.058 (95% CI: 0.02, 0.12). GPT-4 accuracy was improved at 0.15 (95% CI: 0.09, 0.23; P = .02 for accuracy comparison). In recommending PET-CT and/or biopsy, both GPT-3.5 and GPT-4 had an F-score of 0.00. After explicitly including the Fleischner Society guidelines in the prompt, GPT-3.5 and GPT-4 significantly improved their accuracy to 0.42 (95% CI: 0.33, 0.51; P < .001) and to 0.66 (95% CI: 0.57, 0.74; P < .001), respectively. GPT-4 remained significantly better than GPT-3.5 (P < .001). The fine-tuned GPT-3.5 model accuracy was 0.46 (95% CI: 0.37, 0.55), not different from the GPT-3.5 model with guidelines included (P = .53). Conclusion: GPT-3.5 and GPT-4 performed poorly in applying widely known guidelines and never correctly recommended biopsy. Flawed knowledge and reasoning both contributed to their poor performance. While GPT-4 was more accurate than GPT-3.5, its inaccuracy rate was unacceptable for clinical practice. These results underscore the limitations of large language models for knowledge and reasoning-based tasks.

Exploring the Role of Artificial Intelligence in an Emergency and Trauma Radiology Department.

Emergency and trauma radiologists, emergency department's physicians and nurses, researchers, departmental leaders, and health policymakers have attempted to discover efficient approaches to enhance the provision of quality patient care. There are increasing expectations for radiology practices to deliver a dedicated emergency radiology service providing 24/7/365 on-site attending radiologist coverage. Emergency radiologists (ERs) are pressed to meet the demand of increased imaging volume, provide accurate reports, maintain a lower proportion of discrepancy rate, and with a rapid report turnaround time of finalized reports. Thus, rendering the radiologists overburdened. The demand for an increased efficiency in providing quality care to acute patients has led to the emergence of artificial intelligence (AI) in the field. AI can be used to assist emergency and trauma radiologists deal with the ever-increasing imaging volume and workload, as AI methods have typically demonstrated a variety of applications in medical image analysis and interpretation, albeit most programs are in a training or validation phase. This article aims to offer an evidence-based discourse about the evolving role of artificial intelligence in assisting the imaging pathway in an emergency and trauma radiology department. We hope to generate a multidisciplinary discourse that addresses the technical processes, the challenges in the labour-intensive process of training, validation and testing of an algorithm, the need for emphasis on ethics, and how an emergency radiologist's role is pivotal in the execution of AI-guided systems within the context of an emergency and trauma radiology department. This exploratory narrative serves the present-day health leadership's information needs by proposing an AI supported and radiologist centered framework depicting the work flow within a department. It is suspected that the use of such a framework, if efficacious, could provide considerable benefits for patient safety and quality of care provided. Additionally, alleviating radiologist burnout and decreasing healthcare costs over time.

Use of a Multimodal, Peer-to-Peer Learning Management System for Introduction of Critical Clinical Thinking to First-Year Veterinary Students.

Veterinary medical students need multiple thinking strategies, particularly critical thinking. We used a multimedia, peer review learning management system (CGScholar) to introduce a series of complex, realistic, case-based e-learning modules to help introduce critical thinking to 422 first-year veterinary students through instructor-designed clinical cases. Students developed and published on the CGScholar platform an analysis of a case and conducted anonymous peer reviews of each other's drafts. Instructors selected desirable characteristics of a student's activity to track and provide automatic feedback to students via an analytics dashboard and aster plot that allowed visualization of progress. The dashboard also enabled instructors to view the entire class's performance, highlighting students whose performance was lagging. Online interactions were supplemented by case-specific face-to-face workshop sessions. Our goal was to address the following questions: Does the addition of multimedia to a work (one's own or others') enhance people's ability to understand and convey the material? Does peer review (of one's own and others' work) lead to improvements in the writer's own work? Does the peer review process enhance the writer's understanding of what constitutes high-quality literature evidence? An anonymous student survey showed that experience was significantly more positive in the second and third year of implementation after inclusion of explicit guidance on the use of the rubric for peer review. Overall, 67% of students thought inclusion of multimedia enhanced their ability to communicate and 52% agreed multimedia enhanced their ability to understand their peers' analyses, but students were split on benefits to their understanding of high-quality literature.

Encouraging Critical Clinical Thinking (CCT) Skills in First-Year Veterinary Students.

First-year didactic course instructors at the University of Illinois College of Veterinary Medicine leverage earlier clinical rotation experiences with weekly "Clinical Correlations" exercises to provide early exposure to critical clinical thinking (CCT). This study evaluated the efficacy of individual and paired group exercises on CCT development. Before and after instruction, the Cornell Critical Thinking Test (Level Z) (CCTTZ) was administered. Based on the hypothesis that students with higher scores would coach lower-scoring colleagues during group exercises, heterogeneous groups with similar mean scores were established for the year. Students completed 14 individual and paired group exercises over 6 months. Exercises were designed to increase in complexity and decline in scaffolding. Seven of the exercises were cases using the Applied Learning Platform (ALP) at http://www.whenknowingmatters.com . Student analyses were scored according to a six-category critical-thinking rubric using a 5-point scale. Consistent with our hypothesis, individual and group rubric scores increased significantly, plateauing near the end of the year. Contrary to our hypothesis, mean overall CCTTZ scores did not change, but there was a small statistically significant increase in the ability to assess the validity of an argument. Student attitudes were mixed. Positive comments focused on reinforcement of prior didactic instruction, while negative comments focused on preparation time needed to conduct research on clinical concepts, and on a lack of explicit evaluation by summative examinations. Nonetheless, end-of-year GPAs correlated linearly with cumulative individual rubric scores. In summary, the value of early curriculum CCT training was confirmed when discipline-specific criteria were applied.

Society of toxicologic pathology position paper: review series: assessment of circulating hormones in nonclinical toxicity studies: general concepts and considerations.

This is an introductory paper to a series of papers intended to provide the basis for understanding the contribution of endocrine axis disruption or dysfunction to the pathogenesis of morphological findings and to aid in the interpretation of study outcomes. This is the first in this series of guidance papers prepared by the Working Group and outlines general concepts of study design and assay conduct and validation for hormone studies in general.

The feline thyroid gland: a model for endocrine disruption by polybrominated diphenyl ethers (PBDEs)?

The role of polybrominated diphenyl ethers (PBDE) was investigated in the occurrence of feline hyperthyroidism (FH) by evaluating 15 PBDE congeners in serum from 62 client-owned (21 euthyroid, 41 hyperthyroid) and 10 feral cats. Total serum PBDE concentrations in euthyroid cats were not significantly different from those of hyperthyroid cats. Total serum PBDE in feral cats were significantly lower than in either of the groups of client-owned cats. Total serum PBDE did not correlate with serum total T4 concentration. Ten samples of commercial canned cat food and 19 dust samples from homes of client-owned cats were analyzed. Total PBDE in canned cat food ranged from 0.42 to 3.1 ng/g, and total PBDE in dust from 510 to 95,000 ng/g. Total PBDE in dust from homes of euthyroid cats ranged from 510 to 4900 ng/g. In dust from homes of hyperthyroid cats, total PBDE concentrations were significantly higher, ranging from 1100 to 95,000 ng/g. Dust PBDE and serum total T4 concentration were also significantly correlated. Estimates of PBDE exposures calculated from canned cat food and dust data suggest that domestic cats are primarily exposed through ingestion of household dust. These findings indicate further study of the role of PBDE is needed in the development of FH, which might identify the cat as a model and sentinel for humans with toxic nodular goiter (TNG).

Is femoral component rotation in a TKA reliably guided by the functional flexion axis?

BACKGROUND: The position of the femoral component in a TKA in the axial plane influences patellar tracking and flexion gap symmetry. Errors in femoral component rotation have been implicated in the need for early revision surgery. Methods of guiding femoral component rotation at the time of implantation typically are derived from the mean position of the flexion-extension axis across experimental subjects. The functional flexion axis (FFA) of the knee is kinematically derived and therefore a patient-specific reference axis that can be determined intraoperatively by a computer navigation system as an alternative method of guiding femoral component rotation. However, it is unclear whether the FFA is reliable and how it compares with traditional methods. QUESTION/PURPOSES: We asked if the FFA could be measured reproducibly at different stages of the operative procedure; (2) where it lies in relation to a CT-derived gold standard; and (3) how it compares with more traditional methods of judging femoral component rotation. METHODS: Thirty-seven patients undergoing elective TKAs were recruited to the study. Preoperative CT scans were obtained and the transepicondylar axis (TEA) was identified. The TKA then was performed using computer navigation. The FFA was derived before incision and again after the surgical approach and osseous registration. The navigation system was used to register the surgical TEA. The FFA and surgical TEA then were compared with the CT-derived TEA. RESULTS: The mean preincision FFA was similar to the intraoperative FFA and therefore deemed reproducible. We observed no differences in variability between surgical TEA and preincision FFA. The FFA was different from the CT-TEA and judged similar in accuracy to the surgical TEA. CONCLUSION: The reliability and accuracy of the FFA were similar to those of other intraoperative methods. Further evaluation is required to ascertain whether the FFA improves on currently available methods for determining the ideal rotation of the femoral component during TKA.

Arthroscopic stabilization of the shoulder in adolescent athletes participating in overhead or contact sports.

PURPOSE: To investigate the outcome of arthroscopic capsular repair for shoulder instability in an active adolescent population participating in overhead or contact sports. METHODS: We identified 67 patients (aged 13 to 18 years) with post-traumatic recurrent shoulder instability for inclusion in the study from our computer database. Of these patients, 65 (96%) were available for clinical review. There were 44 male and 21 female patients, with a mean age of 16 years at the time of surgery. All patients participated in overhead or contact sports at a competitive level. Arthroscopic capsulolabral repair was performed after at least 6 months of failed nonoperative treatment. The mean follow-up was 63 months. Shoulder range of motion and functional outcomes were measured preoperatively and postoperatively with Single Assessment Numeric Evaluation (SANE), Rowe, and American Shoulder and Elbow Surgeons (ASES) scores. Furthermore, type of sport, time until surgery, and number of dislocations were analyzed from our database to find any correlation with the recurrence rate. RESULTS: At final follow-up, the mean SANE score was 87.23% (range, 30% to 100%) (preoperative mean, 46.15% [range, 20% to 50%]); the mean Rowe score was 85 (range, 30 to 100) (preoperative mean, 35.9 [range, 30 to 50]); and the mean ASES score was 84.12 (range, 30 to 100) (preoperative mean, 36.92 [range, 30 to 48]). The mean forward flexion and external rotation with the arm at 90° abduction did not change from preoperative values; 81% of the patients returned to their preinjury level of sport, and the rate of failure was 21%. The recurrence rate was not related to the postoperative scores (P = .556 for SANE score, P = .753 for Rowe score, and P = .478 for ASES score), the number of preoperative episodes of instability (P = .59), or the time from the first instability episode to the time of surgery (P = .43). There was a statistically significant relation (P = .0021) between recurrence and the type of sport practiced. Recurrence rate was related to the type of sport practiced. CONCLUSIONS: Arthroscopic stabilization is a reasonable surgical option even in an adolescent population performing sports activities. However, it must be emphasized to the patients and their relatives that the recurrence rate that could be expected after an arthroscopic procedure is higher than in the adult population. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Effect of macronutrients, age, and obesity on 6- and 24-h postprandial glucose metabolism in cats.

Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer-(2)H(2)O, [U-(13)C(3)] propionate, and [3,4-(13)C(2)] glucose infusion, and indirect calorimetry-we investigated carbohydrate and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12 old lean, and 12 old obese), each fed three different diets (high protein with and without polyunsaturated fatty acids, and high carbohydrate) in a crossover design. EGP was lowest in fasted and postprandial obese cats despite peripheral insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most important pathway for EGP in all groups, but glycogen contributed significantly. Insulin and leptin concentrations were higher in old than in young lean cats; adiponectin was lowest in obese cats but surprisingly highest in lean old cats. Diet had little effect on metabolic parameters. We conclude that hepatorenal insulin resistance does not develop in the fasted or postprandial state, even in long-term obese cats, allowing the maintenance of euglycemia through lowering EGP. Glycogen plays a major role in EGP, especially in lean fasted cats, and in the postprandial state. Aging may predispose to insulin resistance, which is a risk factor for diabetes in cats. Mechanisms underlying the high adiponectin of healthy old lean cats need to be further explored.

Antimicrobial Prescribing Practices in Dogs and Cats by Colombian Veterinarians in the City of Medellin.

This study surveyed the prescribing behavior of Colombian companion animal veterinarians and compared the responses to the current guidelines of the International Society for Companion Animals on Infectious Diseases (ISCAID). A convenience sample of 100 primary-care veterinary practitioners was selected from the city of Medellin. A questionnaire was designed to present hypothetical clinical scenarios regarding prescription choices for systemic antimicrobials. The numbers of veterinarians empirically prescribing a course of systemic antimicrobials for each scenario were-perioperative elective surgeries (86%), superficial pyoderma (90%), lower urinary tract disease (52%), acute hemorrhagic diarrhea (50%), and kennel cough (46%). For urinary tract disease, cultures and susceptibility testing were only performed by half of the respondents, suggesting lower diagnostic standards. In superficial pyoderma cases, cytology was performed in the following percent of cases-0% (24), 20% (30), 40% (17), 60% (11), 80% (8), and 100% (10). Antimicrobials were over-prescribed relative to emerging standard for elective surgeries (86%), kennel cough (46%), and acute hemorrhagic diarrhea (50%). Critically important antimicrobials, such as fluoroquinolones, were applied commonly for superficial pyoderma (18%), kennel cough (12%), and lower urinary tract disease in dogs (20%) and cats (26%). In conclusion, antimicrobial prescribing behavior was inconsistent with current guidelines, and antimicrobial use could be improved by appropriate diagnostic steps allowing choice of an optimal antimicrobial drug. Overall, we documented the widespread use of antimicrobials for the treatment of these four common disease conditions.

Prevalence of Antimicrobial Resistance in Bacterial Isolates from Dogs and Cats in a Veterinary Diagnostic Laboratory in Colombia from 2016-2019.

The susceptibility to antimicrobials of bacterial isolates from dogs (n = 1256) and cats (n = 94) was retrospectively evaluated in a veterinary diagnostic laboratory over a 4-year period (2016-2019). Out of 1316 isolates in dogs, 771 were Staphylococcus spp. distributed as follows: Staph. pseudointermedius (n = 406), Staph. intermedius (n = 160), Staph. aureus (n = 104), and Staph. coagulase-negative (n = 101). In common, all Staphylococcus spp. showed a high prevalence (20-50%) of resistance to ampicillin, cephalosporin, enrofloxacin, gentamicin, tetracycline, and trimethoprim-sulfonamide, but a low prevalence (1-10%) of resistance to amoxicillin-clavulanate. With regards to the other families of bacteria, the number of antimicrobials for which resistance was high (>20%) in dogs was: Enterobacteriaceae (7/12), Enterococcus spp. (10/16), E. coli (11/15), Pseudomonas spp. (10/13), and Streptococcus spp. (4/9). For urinary tract infections caused by E. coli or Enterobacteriaceae (Klebsiella spp., Proteus spp.), amikacin and florfenicol were the only drugs that demonstrated 100% in vitro efficacy. Multi-drug resistance was observed in 18.7% (246/1316) and 22% (21/97) of the isolates from dogs and cats, respectively. Except for Pseudomonas spp., known for intrinsic resistance, resistance in other bacteria was likely attributed to high selection pressure. In conclusion, empirical antimicrobial use cannot be recommended to treat most common infections, and selection should be based on results from susceptibility testing.

Survey of Pain Knowledge and Analgesia in Dogs and Cats by Colombian Veterinarians.

A questionnaire study was conducted among 131 veterinarians practicing in the city of Medellin, Colombia, to assess views on pain evaluation and management in dogs and cats. When pain recognition and quantification abilities were used as a perceived competence of proper pain assessment, only 83/131 (63.4%, confidence interval (CI) 0.55⁻0.72) were deemed to have satisfactory skills, with the rest considered to be deficient. There were 49/131 (37.4) veterinarians who had participated in continuing education programs and were more confident assessing pain, with an odds ratio (±standard error) of 2.84 ± 1.15 (p = 0.01; CI 1.27⁻6.32). In addition, the odds of using pain scales was 4.28 ± 2.17 (p < 0.01, CI 1.58⁻11.55) greater if they had also participated in continuing education programs. The term multimodal analgesia was familiar to 77 (58.7%) veterinarians who also claimed to use more than one approach to pain control. Nevertheless, homeopathy was the preferred alternative approach in 71/77 (92%). There were major misconceptions on side effects and/or contraindications for use of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) by most veterinarians. In addition, the lack of multimodal analgesia by at least 40% of the practitioners, combined with heavy reliance on weak analgesics (i.e., tramadol) or those with no proven record of efficacy (homeopathic remedies), denotes major deficits in education at the undergraduate level and a need for additional continuing education designed to fulfill the gaps in knowledge identified in this study, and overcome ideological convictions not supported by scientific evidence.

Lower thyroid compensatory reserve of rat pups after maternal hypothyroidism: correlation of thyroid, hepatic, and cerebrocortical biomarkers with hippocampal neurophysiology.

The developing central nervous system of the fetus and neonate is recognized as very sensitive to maternal or gestational hypothyroidism. Despite this recognition, there is still a lack of data concerning the relationship between thyroid-related biomarkers and neurological outcomes. We used propylthiouracil administered at 0, 3, or 10 ppm in drinking water from gestational d 2 until weaning to create hypothyroid conditions to study the relationship between hypothalamic-pituitary-thyroid axis compensation and impaired neurodevelopment. In addition to serum T(3), T(4), free T(4), and TSH concentrations, cerebrocortical T(3) concentration (cT(3)), hepatic type I and cerebrocortical type II (D2) 5'-deiodinase activity, and thyroidal mRNA for thyroglobulin and sodium iodide symporter were measured. Extracellular recordings from the CA1 region in hippocampal slices were obtained from both postnatal d 21-32 (pups) and postnatal d 90-110 (adults) rats to assess neurophysiological effects. Thyroidal mRNA for thyroglobulin and sodium iodide symporter were increased in pups but not in dams. Both propylthiouracil doses increased cerebrocortical D2 activity approximately 5-fold in pups but only 10 ppm increased D2 activity in dams. In dams, cT(3) concentrations were maintained at 3 ppm but fell 75% at 10 ppm. cT(3) concentration in pups fell 50% at 3 ppm and more than 90% at 10 ppm. In both 3 and 10 ppm pups, hippocampal baseline synaptic activity correlated negatively with cerebrocortical D2 activity. In 3 ppm adults, impaired long-term potentiation was evident. In summary, during depletion of serum T(4), D2 activity served as a sensitive marker of tissue thyroid status, an indicator of the brain's compensatory response to maintain cT(3), and correlated with a neurophysiological outcome.

Low-dose effects of ammonium perchlorate on the hypothalamic-pituitary-thyroid axis of adult male rats pretreated with PCB126.

The objective of this research was to characterize the disturbances in the hypothalamic-pituitary-thyroid (HPT) axis resulting from exposure to a binary mixture, 3,3',4,4',5-pentachlorobiphenyl (PCB126) and perchlorate (ClO(4)(-)), known to cause hypothyroidism by different modes of action. Two studies were conducted to determine the HPT axis effects of ClO(4)(-) on adult male Sprague-Dawley rats pretreated with PCB126. In dosing study I, rats were administered a single oral dose of PCB126 (0, 7.5, or 75 microg/kg) on day 0 and 9 days later ClO(4)(-) (0, 0.01, 0.1, or 1 mg/kg day) was added to the drinking water until euthanasia on day 22. Significant dose-dependent trends were found for all thyroid function indices measured following ClO(4)(-) in drinking water for 14 days. Seventy-five micrograms PCB126/kg resulted in a significant increase in hepatic T(4)-glucuronide formation, causing a decline in serum thyroxine and fT(4), and resulting in increased serum thyroid-stimulating hormone (TSH). Serum TSH was also increased in animals that received 7.5 microg PCB126/kg; no other HPT axis alterations were found in these animals. When pretreated with PCB126, the ClO(4)(-) dose trends disappeared, suggesting a less than additive effect on the HPT axis. In dosing study II, animals were given lower doses of PCB126 (0, 0.075, 0.75, or 7.5 microg/kg) on day 0, and followed with ClO(4)(-) (0 or 0.01 mg/kg day) in drinking water beginning on day 1 and continuing for several days to explore transient HPT axis effects. No statistical effects were seen for PCB126 or ClO(4)(-) alone, and no perturbations were found when administered sequentially in dosing study II. In conclusion, these studies demonstrate that HPT axis disturbances following exposure to ClO(4)(-) are less than additive when pretreated with relatively high doses of PCB126. At relatively low doses, at or near the no-observed-effect-level for PCB126 and ClO(4)(-), no interactions between the chemicals occur.

Adults' versus children's perceptions of a child with autism or attention deficit hyperactivity disorder.

The present study examined public perceptions toward children with autism or with attention deficit hyperactivity disorder (ADHD). A convenience sample was used consisting of 30 children (7-12-year-olds) and 30 adults. Participants read a stereotyped scenario featuring either a child with autism, a child with ADHD, or a normal child. Child participants were significantly more likely than adults to (a) express dislike/avoidance toward a child described with either stereotypic autistic or ADHD behaviors, and (b) perceive the child with ADHD as unlike themselves. However, child participants and adults were equally likely to see the autistic child as unlike themselves. Reasons for the different perceptions of children and adults may include differences in perceived threat and in categorization.

Synthetic adrenocorticotropic hormone stimulation tests in healthy neonatal foals.

BACKGROUND: Cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation tests are used to evaluate adrenal function. Low-dose ACTH stimulation tests are the most accurate method for diagnosing relative adrenal insufficiency in critically ill humans but have not been evaluated in foals. HYPOTHESIS: Peak serum cortisol concentrations in healthy foals will not be significantly different after intravenous administration of 1, 10, 100, and 250 microg of cosyntropin. ANIMALS: 14 healthy neonatal foals, 3-4 days of age. METHODS: A randomized cross-over model was used in which cosyntropin (1, 10, 100, or 250 microg) was administered intravenously on days 3 and 4 of life. Blood samples were collected before and 30, 60, 90, 120, and 150 minutes after administration of cosyntropin for determination of serum cortisol concentration. RESULTS: Serum cortisol concentrations did not significantly increase after administration of 1 microg of cosyntropin. Cortisol concentration peaked 30 minutes after administration of 10 microg of cosyntropin and 90 minutes after 100 and 250 microg of cosyntropin. There was no relationship between cosyntropin dose and serum cortisol concentration at 30 minutes. Compared with the 10-microg dose, 100 and 250 microg of cosyntropin induced significantly greater cortisol concentrations at 90 minutes, at which point the 10-microg cosyntropin-dose cortisol values were indistinguishable from baseline. There was no significant difference in the area under the cortisol concentration curve between the 100- and 250-microg doses. No effect of day of testing or foal weight on peak cortisol concentration was detected. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study suggest that 10- and 100-microg doses of cosyntropin would be appropriate for evaluating adrenal function in neonatal foals.

Testing for hypothyroidism in dogs.

Hypothyroidism is the most common endocrinopathy in the dog. Rather than being a comprehensive review of all possible thyroid function tests, the focus in this article is on the logical progression of test choice, highlighting total thyroxine, free thyroxine, triiodothyronine, thyrotropin (TSH), and antithyroid antibodies. This article includes extensive discussion of the current status of the canine TSH assay and the potential for improving this assay.

Effect of PCB 126 on hepatic metabolism of thyroxine and perturbations in the hypothalamic-pituitary-thyroid axis in the rat.

The objective of this research was to examine the time- and dose- dependent disturbances in the hypothalamic-pituitary-thyroid (HPT) axis of adult male rats administered a potent coplanar (non-ortho) PCB, 3,3',4,4',5-pentachlorobiphenyl (PCB 126). Adult male Sprague-Dawley rats were administered a single oral bolus dose of 0, 7.5, 75, or 275 microg PCB 126/kg bw dissolved in corn oil. The rats were sacrificed periodically over 22 days. The 7.5-microg/kg dose induced hepatic ethoxyresorufin-O-deethylation EROD activity, but no changes were observed in hepatic uridine diphosphate glucuronyl transferases (UDPGTs) activity or serum TSH, T4, or fT4 concentrations. The two highest doses caused a modest decline in weight gain, induced hepatic EROD and UDPGT activities, increased serum TSH concentrations, and decreased serum T4 and fT4 concentrations. The amount of thyroxine glucuronide formed daily (pM/mg protein) increased linearly with the area-under-the-concentration-curve (AUCC) for PCB 126 in liver (microg/kg/day) and then slowed at the 275-microg/kg PCB 126 dose. Perturbations in the HPT axis were nonlinear with respect to PCB 126 dosing. As expected, an inverse relationship between the AUCC for serum T4 (microg/dl/day) and the AUCC for serum TSH (ng/dl/day) was observed; however, the relationship was highly nonlinear. These data support a mode of action for PCB 126 involving induction of hepatic UDPGTs by the aryl hydrocarbon receptor AhR. However, the dose-response characteristics of the HPT axis are nonlinear and complex, requiring sophisticated tools, such as PBPK models, to characterize dose response.

Tissue explant coculture model of the hypothalamic-pituitary-gonadal-liver axis of the fathead minnow (Pimephales promelas) as a predictive tool for endocrine disruption.

Endocrine-disrupting compounds (EDCs) can impact the reproductive system by interfering with the hypothalamic-pituitary-gonadal (HPG) axis. Although in vitro testing methods have been developed to screen chemicals for endocrine disruption, extrapolation of in vitro responses to in vivo action shows inconsistent accuracy. The authors describe a tissue coculture of the fathead minnow (Pimephales promelas) HPG axis and liver (HPG-L) as a tissue explant model that mimics in vivo results. Brain (hypothalamus), pituitary, gonad, and liver tissue explants from adult fish were examined for function both individually and in coculture to determine combinations and conditions that could replicate in vivo behavior. Only cocultures had the ability to respond to an EDC, trenbolone, similarly to in vivo studies, based on estradiol, testosterone, and vitellogenin production trends, where lower exposure doses suppressed hormone production but higher doses increased production, resulting in distinctive U-shaped curves. These data suggest that a coculture system with all components of the HPG-L axis can be used as a link between in vitro and in vivo studies to predict endocrine system disruption in whole organisms. This tissue-based HPG-L system acts as a flexible deconstructed version of the in vivo system for better control and examination of the minute changes in system operation and response on EDC exposure with options to isolate, interrogate, and recombine desired components. Environ Toxicol Chem 2016;35:2530-2541. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

2016 AAFP Guidelines for the Management of Feline Hyperthyroidism.

CLINICAL CONTEXT: Since 1979 and 1980 when the first reports of clinical feline hyperthyroidism (FHT) appeared in the literature, our understanding of the disease has evolved tremendously. Initially, FHT was a disease that only referral clinicians treated. Now it is a disease that primary clinicians routinely manage. Inclusion of the measurement of total thyroxine concentration in senior wellness panels, as well as in diagnostic work-ups for sick cats, now enables diagnosis of the condition long before the cat becomes the classic scrawny, unkempt, agitated patient with a bulge in its neck. However, earlier recognition of the problem has given rise to several related questions: how to recognize the health significance of the early presentations of the disease; how early to treat the disease; whether to treat FHT when comorbid conditions are present; and how to manage comorbid conditions such as chronic kidney disease and cardiac disease with treatment of FHT. The 2016 AAFP Guidelines for the Management of Feline Hyperthyroidism (hereafter referred to as the Guidelines) will shed light on these questions for the general practitioner and suggest when referral may benefit the cat. SCOPE: The Guidelines explain FHT as a primary disease process with compounding factors, and provide a concise explanation of what we know to be true about the etiology and pathogenesis of the disease.The Guidelines also:Distill the current research literature into simple recommendations for testing sequences that will avoid misdiagnosis and separate an FHT diagnosis into six clinical categories with associated management strategies.Emphasize the importance of treating all hyperthyroid cats, regardless of comorbidities, and outline the currently available treatments for the disease.Explain how to monitor the treated cat to help avoid exacerbating comorbid diseases.Dispel some of the myths surrounding certain aspects of FHT and replace them with an evidence-based narrative that veterinarians and their practice teams can apply to feline patients and communicate to their owners. EVIDENCE BASE: To help ensure better case outcomes, the Guidelines reflect currently available, evidenced-based knowledge. If research is lacking, or if a consensus does not exist, the expert panel of authors has made recommendations based on their extensive, cumulative clinical experience.