Distal toxic acral erythema and mucositis secondary to 6-mercaptopurine in a thiopurine methyltransferase "super shunter".

Toxic erythema of chemotherapy is a broad but useful diagnosis used to summate the non-infectious, non-allergic, and reproducible reaction of certain chemotherapeutics. Due to overlapping chemotherapy side effects and often multiple drug exposures, identification of a singular culprit drug is challenging for dermatologists. Herein, we report a patient with 6-mercaptopurine (6-MP) toxic erythema confirmed via toxic metabolite markers secondary to increased levels of thiopurine methyltransferase activity, or so called "super shunting." Consulting dermatologists should be aware of "super shunting" in pediatric patients and consider testing for metabolites in patients with toxic acral erythema and mucositis in the setting of 6-MP.

A rare presentation of herpes simplex virus encephalitis occurring in a pediatric patient on dupilumab for atopic dermatitis.

A 4-year-old female with a history of atopic dermatitis developed herpes simplex virus (HSV) encephalitis while being treated with dupilumab and concomitant topical steroids. There was no prior history of HSV infections or immunodeficiency. To our knowledge, this is the first case of HSV encephalitis in a patient receiving dupilumab.

Host-specific parvovirus evolution in nature is recapitulated by in vitro adaptation to different carnivore species.

Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of viral sequences recovered from different wild carnivore species, as shown here, demonstrated that>95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range.

Predicting the odds of chronic wasting disease with Habitat Risk software.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that was first detected in captive cervids in Colorado, United States (US) in 1967, but has since spread into free-ranging white-tailed deer (Odocoileus virginianus) across the US and Canada as well as to Scandinavia and South Korea. In some areas, the disease is considered endemic in wild deer populations, and governmental wildlife agencies have employed epidemiological models to understand long-term environmental risk. However, continued rapid spread of CWD into new regions of the continent has underscored the need for extension of these models into broader tools applicable for wide use by wildlife agencies. Additionally, efforts to semi-automate models will facilitate access of technical scientific methods to broader users. We introduce software (Habitat Risk) designed to link a previously published epidemiological model with spatially referenced environmental and disease testing data to enable agency personnel to make up-to-date, localized, data-driven predictions regarding the odds of CWD detection in surrounding areas after an outbreak is discovered. Habitat Risk requires pre-processing publicly available environmental datasets and standardization of disease testing (surveillance) data, after which an autonomous computational workflow terminates in a user interface that displays an interactive map of disease risk. We demonstrated the use of the Habitat Risk software with surveillance data of white-tailed deer from Tennessee, USA.

Biodetection of an odor signature in white-tailed deer associated with infection by chronic wasting disease prions.

Chronic wasting disease (CWD) has become a major concern among those involved in managing wild and captive cervid populations. CWD is a fatal, highly transmissible spongiform encephalopathy caused by an abnormally folded protein, called a prion. Prions are present in a number of tissues, including feces and urine in CWD infected animals, suggesting multiple modes of transmission, including animal-to-animal, environmental, and by fomite. CWD management is complicated by the lack of practical, non-invasive, live-animal screening tests. Recently, there has been a focus on how the volatile odors of feces and urine can be used to discriminate between infected and noninfected animals in several different species. Such a tool may prove useful in identifying potentially infected live animals, carcasses, urine, feces, and contaminated environments. Toward this goal, dogs were trained to detect and discriminate CWD infected individuals from non-infected deer in a laboratory setting. Dogs were tested with novel panels of fecal samples demonstrating the dogs' ability to generalize a learned odor profile to novel odor samples based on infection status. Additionally, dogs were transitioned from alerting to fecal samples to an odor profile that consisted of CWD infection status with a different odor background using different sections of gastrointestinal tracts. These results indicated that canine biodetectors can discriminate the specific odors emitted from the feces of non-infected versus CWD infected white-tailed deer as well as generalizing the learned response to other tissues collected from infected individuals. These findings suggest that the health status of wild and farmed cervids can be evaluated non-invasively for CWD infection via monitoring of volatile metabolites thereby providing an effective tool for rapid CWD surveillance.

Predicting chronic wasting disease in white-tailed deer at the county scale using machine learning.

Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .

A PRELIMINARY INVESTIGATION OF PATHOGEN EXPOSURE OF ADULT FEMALE WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) AND SURVIVAL OF ASSOCIATED FAWNS IN THE WESTERN DAKOTAS, USA.

Exposure of a dam to pathogens may potentially affect her fawns positively or negatively. Mammalian females transfer immunologic protection to their offspring via colostrum obtained while nursing. Conversely, chronic diseases in dams may potentially result in small and weak neonates, reduced milk production or quality, or infection. Little is known about how pathogen exposure in adult female white-tailed deer (Odocoileus virginianus) affects offspring survival. Our objective was to assess pathogen exposure for female white-tailed deer and subsequent survival rates of fawns in Dunn and Grant counties, North Dakota, and Perkins County, South Dakota, USA. We collected blood serum from 150 adult female deer during 2014. We compared survival of 49 fawns to maternal exposure to 10 pathogens from 37 of 150 adult females. There was no difference in fawn mass between dams based on antibody status and no difference in fawn survival for nine pathogens. The 12-wk survival for fawns born to mothers with antibodies against bovine herpesvirus 1 (BoHV-1, causing infectious bovine rhinotracheitis) was lower than for fawns born from mothers without antibodies against BoHV-1; however, the indirect or direct impacts of BoHV-1 exposure in mothers on fawn survival are unclear. Although our findings suggest that the cost of exposure to previous diseases may have minimal impact on short-term fawn survival for most pathogens, additional research with increased sample sizes is needed to confirm our findings.

Exposure to Select Pathogens in an Expanding Moose (Alces alces) Population in North Dakota, USA.

Forty female moose (Alces alces) captured in North Dakota, US, in March 2014 were tested for antibodies to a variety of pathogens. Antibodies to West Nile virus (WNV) were detected in 39 (98%) moose following a year with a high number of human cases, suggesting the population accurately reflects WNV activity. Fifteen percent of moose (6/40) had antibodies to Borrelia burgdorferi, implying expansion of the tick vector into the area. Antibodies to Anaplasma spp. were detected in 55% of moose (22/40), a higher rate than previously detected in cattle from the region. Low titers (100-400) to one or more serovars of Leptospira spp. were detected in 23% of moose (9/40), a common finding in wild ruminants. Exposure to other pathogens was uncommon (<8%; <3/40) or not documented. Survival and recruitment were high during the study period, suggesting a limited population-level impact at current levels of exposure and environmental co-stressors.

Rapid Discovery and Detection of Haemaphysalis longicornis through the Use of Passive Surveillance and Collaboration: Building a State Tick-Surveillance Network.

Between March 2019 and February 2020, Asian long-horned ticks (Haemaphysalis longicornis Neumann, 1901) were discovered and collected for the first time in one middle and seven eastern Tennessee counties, facilitated by a newly developed passive and collaborative tick-surveillance network. Network collaborators included federal, state, county, university, and private resource personnel working with companion animals, livestock, and wildlife. Specimens were collected primarily from dogs and cattle, with initial detections of female adult stage ticks by stakeholders associated with parasitology positions (e.g., entomologists and veterinary parasitologists). Initial county tick detections were confirmed with morphological and molecular identifications, and then screened for the presence of animal-associated pathogens (Anaplasma marginale, Babesia species, Ehrlichia species, and Theileria orientalis), for which all tests were negative. Herein, we describe the identification and confirmation of these tick specimens as well as other results of the surveillance collaboration.

Takotsubo cardiomyopathy triggered by SARS-CoV-2 infection in a critically ill patient.

COVID-19 became a global pandemic in early 2020. While well known for its pulmonary manifestations, the virus also has a number of cardiac manifestations as well. Takotsubo syndrome has scarcely been reported in patients with COVID-19, but it is possible that the cytokine storm associated with the infection can trigger Takotsubo syndrome in patients with underlying risk factors for Takotsubo (emotional distress, physical distress, history of psychiatric disorders).

Development of Bronchopleural Fistula Complicated by Empyema Fifteen Years After Right Lower Lobe Lobectomy: A Case Report.

BACKGROUND Bronchopleural fistula formation is a rare complication of lobectomy surgery, with a frequency reported ranging from 0.5% to 1%. A post-lobectomy bronchopleural fistula usually presents within 14 days of surgery. To our knowledge, it is extremely rare for a bronchopleural fistula to develop many years after an operation. CASE REPORT We present the case of a 55-year-old male smoker with history of a right lower lobe lobectomy 15 years prior who presented to the Emergency Department with complaints of worsening back pain, shortness of breath, and cough productive of sputum. He was found to have a right bronchopleural fistula with right-sided empyema. He was taken to the operating room a few days after initial admission for right thoracoscopic chest exploration, right chest debridement, right chest wall resection, and window procedure with creation of pleurocutaneous fistula. Ultimately, he required a right completion pneumonectomy and buttress of bronchial stump with transdiaphragmatic omental flap. CONCLUSIONS We diagnosed a rare case of post-lobectomy bronchopleural fistula complicated by an empyema that demonstrates bronchopleural fistulas can appear 15 years postoperatively and present with subacute clinical signs and symptoms.

Seborrhea herpeticum: cutaneous herpes simplex virus infection within infantile seborrheic dermatitis.

Eczema herpeticum has been well described in the setting of atopic dermatitis (AD) and other dermatoses. We present the case of a 2-month-old infant boy with cutaneous herpes simplex virus (HSV) infection within existing diffuse infantile seborrheic dermatitis. Providers should be aware that cutaneous HSV can be confined to a seborrheic distribution and may represent underlying epidermal dysfunction secondary to seborrheic dermatitis.

Effects of Neonicotinoid Insecticides on Physiology and Reproductive Characteristics of Captive Female and Fawn White-tailed Deer.

Over the past decade, abnormalities have been documented in white-tailed deer (Odocoileus virginianus) in west-central Montana. Hypotheses proposed to explain these anomalies included contact with endocrine disrupting pesticides, such as imidacloprid. We evaluated the effects of imidacloprid experimentally at the South Dakota State University Wildlife and Fisheries Captive Facility where adult white-tailed deer females and their fawns were administered aqueous imidacloprid (an untreated control, 1,500 ng/L, 3,000 ng/L, and 15,000 ng/L). Water consumption, thyroid hormone function, behavioral responses, and skull and jawbone measurements were compared among treatments. Additionally, liver, spleen, genital, and brain imidacloprid concentrations were determined by an enzyme-linked immunosorbent assay (ELISA). Results indicated that 1) control deer consumed more water than treatment groups, 2) imidacloprid was present in the organs of our control group, indicating environmental contamination, 3) as imidacloprid increased in the spleen, fawn survival, thyroxine levels, jawbone lengths, body weight, and organ weights decreased, 4) adult female imidacloprid levels in the genitals were negatively correlated with genital organ weight and, 5) behavioral observations indicated that imidacloprid levels in spleens were negatively correlated with activity levels in adult females and fawns. Results demonstrate that imidacloprid has direct effects on white-tailed deer when administered at field-relevant doses.

Why does the heart beat? The discovery of the electrical system of the heart.

Why does the heart beat? This question--known as the myogenic versus neurogenic theory--dominated cardiac research in the 19th century. In 1839, Jan Evangelista Purkinje discovered gelatinous fibers in the ventricular subendocardium that he thought were muscular. Walter Gaskell, in 1886, demonstrated specialized muscle fibers joining the atria and ventricles that caused "block" when cut and found that the sinus venosus was the area of first excitation of the heart. By examining serial embryologic sections, Wilhelm His, Jr, showed that a connective tissue sheet became a bundle connecting the upper and lower cardiac chambers, the bundle of His. Sunao Tawara traced the atrioventricular (AV) bundle of His backward to find a compact node of fibers at the base of the atrial septum and forward where it connected with the bundles of cells discovered by Purkinje in 1839. Tawara concluded that this "AV connecting system" originated in the AV node, penetrated the septum as the His bundle, and then divided into left and right bundle branches that terminated in the Purkinje fibers. Martin Flack and Arthur Keith studied the conduction system of a mole and found a structure in the sinoauricular junction that histologically resembled the AV node. They felt that this was where "the dominating rhythm of the heart normally begins" and named it the sinoauricular node in 1907. The ECG of Einthoven soon brought a new understanding to the complex electrical system that makes the heart beat. In 2006 and 2007, we celebrate the 100th anniversaries of the publication of the exciting discovery of the AV and sinus nodes, truly landmarks in our understanding of cardiac structure and physiology.

Surgical technique for tubal ligation in white-tailed deer (Odocoileus virginianus).

Surgical tubal ligation was used to sterilize urban free-ranging white-tailed deer (Odocoileus virginianus) as a methodology of a larger study investigating the influences of intact, sterile females on population dynamics and behavior. Deer were either trapped in clover traps (n = 55) and induced with an i.m. injection of xylazine and tiletamine/zolazepam or induced by a similar protocol by dart (n = 12), then intubated and maintained on isoflurane in oxygen. Over 3 yr, individual female deer (n = 103) were captured in Highland Park, Illinois, with a subset of females sterilized using tubal ligation by ventral laparotomy (n = 63). Other sterilization procedures included tubal transection by ventral (n = 1) or right lateral (n = 2) laparoscopy and ovariohysterectomy by ventral laparotomy (n = 1). One mortality (1/ 67, 1.5%) of a doe with an advanced pregnancy was attributed to a lengthy right lateral laparoscopic surgery that was converted to a right lateral laparotomy. The initial surgical modality of laparoscopy was altered in favor of a ventral laparotomy for simplification of the project and improved surgical access in late-term gravid does. Laparotomy techniques included oviductal ligation and transection (n = 14), application of an oviductal mechanical clip (n = 9), ligation and partial salpingectomy (n = 40), and ovariohysterectomy (n = 1). As of 2 yr poststerilization, no surgical does were observed with fawns, indicating that these procedures provide sterilization with low mortality in urban white-tailed deer.

Combined infection by avian poxvirus and Collyriclum faba in an American crow (Corvus brachyrhynchos).

An adult American crow (Corvus brachyrhynchos) from Virginia, USA, was diagnosed with combined infection of avian poxvirus and the skin fluke Collyriclum faba. The flukes and viral inclusions were combined in a large (4 x 4 cm) multilobulated proliferative mass on the ventrum just cranial to the cloaca. The flukes were identified using light microscopy of organisms obtained by antemortem wedge biopsy. Intraepithelial cytoplasmic inclusions consistent with poxvirus infection were seen on histopathologic examination of the mass.