PRELIMINARY EVALUATION OF SYMMETRIC DIMETHYLARGININE AS A BIOMARKER OF RENAL INSUFFICIENCY IN WILD AND REHABILITATED FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS).

Currently, there are limited antemortem tests available to evaluate renal function in Florida manatees (Trichechus manatus latirostris). Although few reports of renal pathology in manatees exist in the veterinary literature, debilitated animals that present to rehabilitation centers are frequently dehydrated, may have sustained renal trauma secondary to watercraft injury, and may experience ischemic events related to coagulation disorders leading to renal compromise. Clinicians remain limited to the analysis of blood urea nitrogen, creatinine levels, and urinalysis (if urine is obtained) to determine the extent of renal insufficiency, which may not accurately reflect renal function. This poses a diagnostic challenge for clinicians in discerning how critical renal compromise is to the animal's overall health and prognosis. For the first phase of this study, retrospective symmetric dimethylarginine (SDMA) values were determined from banked serum or plasma samples from 14 wild Florida manatees that had been collected while the animals were under rehabilitation in zoological institutions prior to their deaths. Values of SDMA for nine samples from eight manatees with known renal disease, as determined by histopathology, were compared to SDMA values for seven samples from six manatees with no reported renal lesions on histopathology. Values of SDMA from wild Florida manatees with known renal disease (mean 33.56 µg/dl ± 13.15, P= 0.017) were statistically significantly elevated when compared to SDMA values from manatees with no reported renal lesions (mean = 18.71 µg/dl ± 6.9) on histopathology. For the second phase of the study, serum or plasma samples were obtained from wild manatee populations from two geographically separate presumed-healthy wild manatee populations (n = 57). Although the upper limit was higher, serum SDMA concentrations from presumed-healthy wild manatees were comparable to those reported in small animal and equine medicine at 5.88-16.97 µg/dl.

EVALUATION OF THE PHARMACOKINETIC BEHAVIOR OF TULATHROMYCIN (DRAXXIN) IN FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS) UNDERGOING MEDICAL REHABILITATION.

Florida manatees (Trichechus manatus latirostris) frequently present to rehabilitation care facilities for various conditions, including boat strike trauma, cold stress syndrome, and brevetoxicosis. Throughout the course of treatment, antimicrobial use to treat respiratory disease is frequently warranted. To date, clinicians have extrapolated dosages based on established information available in bovine and equine medicine. The routes of administration, efficacy, and treatment intervals are considerations in dealing with critical wild animals. The use of tulathromycin, a triamilide antibiotic, has been studied in multiple domestic species of economic importance, including cattle, small ruminants, and swine, and has revealed efficacy against respiratory diseases. Given this information, this antibiotic has also been used in manatees with positive clinical outcomes. This study employed sparse sampling and evaluated banked plasma samples at various time intervals post-tulathromycin administration obtained during the clinical treatment course of nine animals during their rehabilitation. Preliminary pharmacokinetic analysis following administration of a single dose estimated a half-life of 33.75 h and volume of distribution per fraction absorbed (Vz/F = 4.29 L/kg). The pharmacokinetic behavior of tulathromycin in Florida manatees can be used to optimize dosage regimens in this species.

Adapting Existing Resources for Serious Illness Communication Skills Training for Internal Medicine Residents.

OBJECTIVES: Goals of care discussions are a vital component of patient care, but Internal Medicine residents receive limited training in these skills. Existing curricula often require simulated patients or faculty development, limiting implementation in many residency programs. Thus, we developed and implemented a curriculum leveraging existing educational resources with the goal of improving resident attitudes and confidence in conducting goals of care discussions in training settings. METHODS: We developed cases and a detailed faculty guide for small-group discussion with three exercises to standardize the learner experience and minimize the need for faculty development. Exercises introduced established communication skill frameworks including SPIKES (setting, perception, invitation, knowledge, empathy, summary) and REMAP (reframe, emotion, map, align, propose a plan) for how to break bad news, respond to strong emotions, and conduct a goals of care discussion. Participants were 163 Internal Medicine postgraduate year 1, -2, and -3 residents at a large urban academic institution, where residency-wide curriculum is delivered in weekly half-day didactic sessions during the course of 5 weeks. Primary outcomes were resident self-reported confidence with goals of care communication skills. RESULTS: A total of 109 (response rate 67%) of residents reported improvement in overall confidence in goals of care discussion skills (3.6 ± 0.9 vs 4.1 ± 0.6, P < 0.001), responding to emotions (3.5 ± 0.9 vs 3.9 ± 0.6, P = 0.004), making care recommendations (3.5 ± 1.0 vs 3.9 ± 0.7, P < 0.001), and quickly conducting a code status discussion (3.6 ± 1.0 vs 4.0 ± 0.7, P < 0.001). Residents also expressed an increased desire for supervision and feedback to further develop these skills. CONCLUSIONS: This goals of care communication curriculum improves resident confidence and requires minimal resources. It may be ideal for programs that have limited access to simulated patients and/or faculty trained in communication skill simulation, but desire enhanced education on this important aspect of patient-doctor communication and high-quality patient care. Future studies measuring clinical outcomes and changes in learner behavior as a result of this intervention are needed. Ongoing observation and feedback on these skills will be important to solidify learning and sustain impact.

Promising and Upcoming Treatments in Myositis.

PURPOSE OF REVIEW: To highlight new and emerging treatment targets in myositis. RECENT FINDINGS: The landscape of novel therapeutics in myositis has vastly changed in the past 5 years. This is largely due to a greater understanding of the pathogenesis of myositis and validation of more robust outcome measures that standardize the ability to assess treatment response. Clinical trials in dermatomyositis are leading the way with ongoing multicenter, international phase 3 clinical trials. Proof-of-concept studies targeting the JAK/STAT pathway have also showed early promise in treating refractory dermatomyositis in adults and children. This review highlights that the future armamentarium of therapeutic drugs will likely be larger and more selective in treating different subgroups of myositis.

Micro-computed tomography as a platform for exploring Drosophila development.

Understanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering the mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here, we present an accessible method for non-invasive imaging of Drosophila melanogaster at high resolution using micro-computed tomography (µ-CT). We show how rapid processing of intact animals, at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use µ-CT imaging to study growth defects in the Drosophila brain through the characterization of abnormal spindle (asp) and WD repeat domain 62 (Wdr62), orthologs of the two most commonly mutated genes in human microcephaly patients. Our work demonstrates the power of combining µ-CT with traditional genetic, cellular and developmental biology tools available in model organisms to address novel biological mechanisms that control animal development and disease.

Acute Myocardial Infarction Readmission Risk Prediction Models: A Systematic Review of Model Performance.

BACKGROUND: Hospitals are subject to federal financial penalties for excessive 30-day hospital readmissions for acute myocardial infarction (AMI). Prospectively identifying patients hospitalized with AMI at high risk for readmission could help prevent 30-day readmissions by enabling targeted interventions. However, the performance of AMI-specific readmission risk prediction models is unknown. METHODS AND RESULTS: We systematically searched the published literature through March 2017 for studies of risk prediction models for 30-day hospital readmission among adults with AMI. We identified 11 studies of 18 unique risk prediction models across diverse settings primarily in the United States, of which 16 models were specific to AMI. The median overall observed all-cause 30-day readmission rate across studies was 16.3% (range, 10.6%-21.0%). Six models were based on administrative data; 4 on electronic health record data; 3 on clinical hospital data; and 5 on cardiac registry data. Models included 7 to 37 predictors, of which demographics, comorbidities, and utilization metrics were the most frequently included domains. Most models, including the Centers for Medicare and Medicaid Services AMI administrative model, had modest discrimination (median C statistic, 0.65; range, 0.53-0.79). Of the 16 reported AMI-specific models, only 8 models were assessed in a validation cohort, limiting generalizability. Observed risk-stratified readmission rates ranged from 3.0% among the lowest-risk individuals to 43.0% among the highest-risk individuals, suggesting good risk stratification across all models. CONCLUSIONS: Current AMI-specific readmission risk prediction models have modest predictive ability and uncertain generalizability given methodological limitations. No existing models provide actionable information in real time to enable early identification and risk-stratification of patients with AMI before hospital discharge, a functionality needed to optimize the potential effectiveness of readmission reduction interventions.

Predictors of Placement of Inpatient Palliative Care Consult Orders Among Patients With Breast, Lung, and Colon Cancer in a Safety Net Hospital System.

BACKGROUND: The provision of palliative and end-of-life care to patients who are underrepresented and underserved provides unique challenges and opportunities. OBJECTIVES: To examine predictors of placement of inpatient palliative care consult orders among patients with breast, lung, and colorectal cancer hospitalized in a safety net hospital in 2010. METHODS: Simple and multivariable logistic regression of data on selected patients with cancer was performed to identify predictors of placement of inpatient palliative care consult orders. RESULTS: Of 979 patients, 56% had colorectal cancer, 23% had lung cancer, and 21% had breast cancer. Of those patients, 16% received an order for inpatient palliative care consultation during the study period. Patients who had more than 20 prescriptions for opioids ordered (adjusted odds ratio [AOR]: 9.10, 95% confidence interval [CI]: 4.62-17.95), had an order for a radiation oncology consult (AOR: 2.60, 95% CI: 1.50-4.49), or had low albumin (AOR: 2.75, 95% CI: 4.71) were more likely to have an order for an inpatient palliative care consult placed. Race and ethnicity were not statistically significant predictors. CONCLUSION: In this cohort of patients in a safety net hospital, markers of pain, advanced disease, and poor prognosis were associated with placement of inpatient palliative care consult orders.

Identification of Factors Affecting Fecal Pollution in Beaver Lake Reservoir.

Standard methods for the evaluation of recreational water quality rely on generic bacterial indicators such as . However, does not provide enough information to determine fecal source or public health risk. The stsudy objective was to determine factors influencing the presence of and host-specific markers (HSM) from upstream to downstream in Beaver Lake Reservoir (BLR). From February 2014 to September 2015, 420 base flow and rain event samples were collected from seven sites-two sites from streams (White River [WR] and War Eagle Creek) draining into BLR and five sites from within BLR. Each sample was analyzed for and by quantitative polymerase chain reaction for HSM related to human, bovine, and poultry. The data indicate that overall levels of were significantly greater in the WR and significantly lower at the most downstream sampling location in BLR. is more likely present during spring (adjusted odds ratio [aOR] = 1.86), at the WR sampling site (aOR = 3.39), or during a rain event (aOR = 2.73). Moreover, the HSM HumM2 is more likely present (aOR = 1.99) when is present. These same factors were associated with concentrations >126 most probable number 100 mL (aOR = 2.76-12.48), except the poultry marker CL was more likely associated (aOR = 3.81) than HumM2. This study revealed that both seasonal and locational factors are important variables for fecal pollution in BLR. Moreover, these same factors may apply to fecal pollution in manmade reservoirs within similar types of watersheds across the United States, as well as internationally.

Disseminated toxoplasmosis Toxoplasma gondii in a wild Florida manatee Trichechus manatus latirostris and seroprevalence in two wild populations.

Marine mammals are important indicators for ecosystem health and serve as sentinel species for infectious agents including zoonoses. Histological examination of tissues from a stranded Florida manatee Trichechus manatus latirostris revealed protozoal cysts in the cerebrum and intrahistiocytic tachyzoites in the liver and caudal mesenteric lymph node. Disseminated Toxoplasma gondii infection was confirmed by immunohistochemistry and sequencing of the nuclear ribosomal internal transcribed spacer region of formalin-fixed tissues. The lack of baseline information on Florida manatees' exposure to this pathogen prompted a study into the seroprevalence of T. gondii in 2 separate geographic habitats in Florida, USA, during the winters from 2011-2014. Serum was collected during routine health assessments of 44 apparently healthy manatees from Crystal River (n = 26) on the west central coast of Florida and Brevard County (n = 18) on the east coast of Florida. Serum was screened for detection of T. gondii immunoglobulin G (IgG) antibodies via the modified agglutination test. Two animals from Crystal River from 2011 and 2012 (7.7%) and one animal from Brevard County from 2011 (5.6%) tested positive for T. gondii antibodies. Overall seroprevalence for T. gondii was low in the 2 sampled populations and may reflect a low seroprevalence or animal susceptibility. However, continued monitoring of this pathogen in aquatic ecosystems is warranted due to both possible anthropogenic sources and zoonotic potential.

REPRODUCTIVE NEOPLASMS IN WILD AND LONG-TERM CAPTIVE FEMALE FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS).

Few reports of neoplastic diseases in manatees exist in the veterinary literature. This case series presents reproductive neoplasia noted in eight wild and long-term captive female Florida manatees (Trichechus manatus latirostris) obtained through carcass recovery and animal rehabilitation programs between April 2009 and May 2014. All cases were evaluated histologically, and diagnoses of uterine carcinoma (n = 1), granulosa cell tumor (n = 2), ovarian adnexal tumor (n = 1), and leiomyoma (n = 5) were made. The underlying cause of tumor development and effects on reproductive success is currently unknown, but possible asymmetric reproductive aging and/or a correlation between obesity and reproductive disorder in long-term nonreproductive female manatees are of interest and warrant further investigation.