EFFICACY OF HUMAN RECOMBINANT GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF, FILGRASTIM; NEUPOGEN®) IN NEUTROPENIC CETACEANS.

Neutrophils are one of the initial cell lines of protection against pathogens, and when their concentrations in the blood are low, animals are highly susceptible to infections. Neutropenia has been reported in cetaceans secondary to administration of systemic sulfa antibiotics or antifungal medications and severe, overwhelming infection. Filgrastim was administered to treat neutropenia over a 15-y period in 11 cetaceans comprising four species-beluga (Delphinapterus leucas, n = 1), bottlenose dolphin (Tursiops truncatus, n = 4), killer whale (Orcinus orca, n = 5), and short-finned pilot whale (Globicephala macrorhynchus, n = 1)] ranging in age from 1 wk to >24 y. Seven study animals received multiple doses (2-6). All animals responded to at least one dose (1-7 µg/kg) of parenteral filgrastim characterized by an increase in peripheral immature (band) neutrophils, segmented neutrophils, or both. In most cases (9/11), neutrophil counts increased within 48 h of a single dose. Duration of response varied but was at least 2 wk in eight of the 11 animals and 5-9 d in the remaining animals. No adverse reactions were observed in any cases.

AUDITORY EVOKED POTENTIALS AND BEHAVIORAL CONSIDERATIONS WITH HEARING LOSS IN SMALL CETACEANS: APPLICATION AS A STANDARD DIAGNOSTIC TEST IN HEALTH ASSESSMENT.

The primary sense in odontocetes is hearing and a large portion of the odontocete brain is devoted to the auditory processing of echolocation signals. Hearing deficits in odontocetes potentially compromise the ability to forage, navigate, socialize, and evade predators. This presents a challenge to survival and reproduction in wild odontocetes and can affect the general welfare of odontocetes under human care. Currently, little empirical information on how odontocete behavior is affected by hearing loss exists. This study investigated hearing deficits in several species of stranded dolphins and age-related hearing deficits in dolphins kept under human care through auditory evoked potential (AEP) testing and evaluated whether individual behavior correlated with hearing impairment. Behavioral questionnaires for participating animals were completed by individuals with extensive knowledge of the animals' history and behavior. A chi-square analysis determined whether animals with hearing impairment demonstrated behaviors that differed significantly from those considered normal. All tested individuals under human care over 35 years of age had some degree of hearing loss, as did a large percentage of previously stranded animals. Individuals with hearing loss exhibited a range of behavioral changes, including delays in learning new behaviors, accepting novel enrichment, and habituating to new environments. Some individuals with profound hearing loss also displayed a change in vocalization rate in various situations. Findings within previously stranded animals suggest AEP studies should be conducted in all stranded individuals entering rehabilitation. It is further recommended that dolphins living under human care undergo hearing tests as part of their normal health assessments, with emphasis on aging individuals and animals that exhibit delayed learning, respond poorly to audible cues, or show atypical vocalization behavior.

Successful treatment of stage IVB ovarian carcinosarcoma with PARP Inhibitor: A case report.

•Ovarian carcinosarcoma is a rare ovarian cancer histology that has limited treatment options.•In this study, we present an unusual association between carcinosarcoma and a STIC lesion.•In select patients with carcinosarcoma, PARP inhibition may provide clinical benefit.

Production of live offspring following unilateral (left) ovariectomized Potamotrygon rays (Potamotrygon castexi, Potamotrygon leopoldi, and Potamotrygon motoro).

OBJECTIVE: To evaluate the surgical technique and subsequent clinical observations (reproductive and ultrasound findings) of left unilateral ovariectomy in 3 species of Potamotrygon rays-Potamotrygon castexi, Potamotrygon leopoldi, and Potamotrygon motoro-for reproductive management. ANIMALS: Between 2018 and 2019, multiple Potamotrygon rays (P castexi, n = 1; P leopoldi, 1; P motoro, 6) underwent left ovariectomies to evaluate this technique for reproductive management. PROCEDURES: At time of surgery, patient age ranged from juvenile to adult. Rays were anesthetized with MS222 buffered with sodium bicarbonate, and a left craniodorsal surgical approach was made to isolate and excise the left ovary. All rays had uneventful recoveries. Eight unilateral ovariectomized females and 6 males were combined in a mixed-species freshwater touch pool of Potamotrygon rays and teleost species. RESULTS: In December 2020, 3 live and 1 premature autolyzed pup were noted in the habitat. The following day, the adult females were examined via ultrasound and separated from the males. Four dams were identified that produced 8 viable offspring and 4 premature abortions. A large right ovary was observed in all females, with no evidence of left ovarian tissue present via ultrasound. CLINICAL RELEVANCE: Previous histologic evaluation of freshwater ray ovarian tissue suggests both ovaries may be functionally active yet maintain left dominance like some other elasmobranch species. This manuscript provides proof the right ovary alone can produce live offspring. Furthermore, the enlarged right ovary observed in these females suggests that removal of the left ovary may result in compensatory enlargement of the right ovary.

Endometrial Cancer Risk Among Germline BRCA1/2 Pathogenic Variant Carriers: Review of Our Current Understanding and Next Steps.

PURPOSE: To review the literature exploring endometrial cancer (EC) risk among surgical candidates with germline BRCA1/2 pathogenic variants (PVs) to guide decisions around risk-reducing (rr) hysterectomy in this population. DESIGN: A comprehensive review was conducted of the current literature that influences clinical practice and informs expert consensus. We present our understanding of EC risk among BRCA1/2 PV carriers, the risk-modifying factors specific to this patient population, and the available research technology that may guide clinical practice in the future. Limitations of the existing literature are outlined. RESULTS: Patients with BRCA1/2 PVs, those with a personal history of tamoxifen use, those who desire long-term hormone replacement therapy, and/or have an elevated BMI are at higher risk of EC, primarily endometrioid EC and/or uterine papillary serous carcinoma, and may benefit from rr-hysterectomy. Although prescriptive clinical guidelines specific to BRCA1/2 PV carriers could inform decisions around rr-hysterectomy, limitations of the current literature prevent more definitive guidance at this time. A large population-based study of a contemporary cohort of BRCA1/2 PV carriers with lifetime follow-up compared with cancer-gene negative controls would advance this topic and facilitate care decisions. CONCLUSION: This review validates a potential role for rr-hysterectomy to address EC risk among surgical candidates with BRCA1/2 PVs. Evidence-based clinical guidelines for rr-hysterectomy in BRCA1/2 PV carriers are essential to ensure equitable access to this preventive measure, supporting insurance coverage for patients with either BRCA1 or BRCA2 PVs to pursue rr-hysterectomy. Overall, this review highlights the complexity of EC risk in BRCA1/2 PV carriers and offers a comprehensive framework to shared decision making to inform rr-hysterectomy for BRCA1/2 PV carriers.

Comparison of laryngeal mask airway use with endotracheal intubation during anesthesia of western lowland gorillas (Gorilla gorilla gorilla).

The laryngeal mask airway is an alternative to endotracheal intubation that achieves control of the airway by creating a seal around the larynx with an inflatable cuff. This study compared use of the laryngeal mask airway with endotracheal intubation in anesthetized western lowland gorillas (Gorilla gorilla gorilla). Eight adult gorillas were immobilized for routine and diagnostic purposes for a total of nine anesthetic events. During each anesthetic event, gorillas were either intubated (n = 4; group A) or fitted with a laryngeal mask airway (n= 5; group B). Time required to place each airway device, physiologic parameters, and arterial blood gas were measured and compared between the two groups. There were no significant differences between the two groups for time required to place airway device, heart rate, hemoglobin oxygen saturation, end-tidal carbon dioxide, arterial partial pressure of carbon dioxide, or arterial pH between the two groups. Mean arterial partial pressure of oxygen was significantly greater in group B, 15 (group A: 94 +/- 44 mm Hg; group B: 408 +/- 36 mm Hg; P= 0.0025) and 45 (group A: 104 +/- 21 mm Hg; group B: 407 +/- 77 mm Hg; P = 0.0026) min after airway device placement. Mean respiratory rate was significantly greater in group A at multiple time points. Mean arterial pressure (group A: 129 +/- 16 mm Hg; group B: 60 +/- 8 mm Hg) and diastolic blood pressure (group A: 115 +/- 21 mm Hg; group B: 36 +/- 10 mm Hg) were significantly greater in group A at the time of airway device placement. The laryngeal mask airway maintained oxygenation and ventilation effectively in all gorillas and is a useful alternative to endotracheal intubation in western lowland gorillas.

Primary feather follicle ablation in common pintails (Anas acuta acuta) and a white-faced whistling duck (Dendrocygna viduata).

Eight 1-yr-old common pintails (Anas acuta acuta) and one 2-yr-old white-faced whistling duck (Dendrocygna viduata) were presented for the persistence of primary flight feathers 1 yr after pinioning. The birds were housed outdoors in an open enclosure necessitating flight prevention. The birds were placed under general anesthesia, and a diode laser was used to ablate the primary feather follicles of the previously pinioned wing. Swelling was the most common side effect seen in seven out of nine treated birds. Other side effects included ulceration, hyperemia, edema, and serosanguinous discharge. All side effects were resolved by 12 wk postprocedure. Laser feather follicle ablation was successful in 28 of 40 (70%) of the treated common pintail feathers, and flight was not observed 7 mo following the procedure in any of these birds. Feather follicle ablation was successful in two of six (33%) of the treated white-faced whistling duck feathers, and the bird in question was observed flying 5 mo after the procedure. Primary feather follicle ablation with a diode laser was a successful method of flight prevention in common pintails but was not effective for a white-faced whistling duck.

Evaluation of gastroscopic biopsy for diagnosis of Cryptosporidium sp. infection in snakes.

Cryptosporidium sp. is a protozoal parasite that can cause hypertrophic gastritis, regurgitation, and chronic wasting in snakes. Diagnosis can be challenging because of intermittent shedding of the organism in the feces. The purpose of this study was to evaluate gastroscopic biopsy as a diagnostic method for Cryptosporidium sp. screening during an outbreak at the Oklahoma City Zoo. Twenty-two snakes were immobilized by chamber induction with an inhalant anesthetic. Gross lesions were seen in seven snakes and consisted of hyperemia, thickening of the gastric mucosa as observed by lack of rugal folds, and a cobblestoned appearance. Gastric biopsy was performed for histologic evaluation (n = 21). Hypertrophic gastritis with intralesional cryptosporidia was diagnosed in five animals. Eleven animals died or were euthanized and complete necropsy was used to evaluate diagnostic measurements of performance of gastric biopsy. Sensitivity for gastric biopsy was 71.4% and specificity was 100%. Gastroscopy appears to be a useful diagnostic method for Cryptosporidium infection in snakes and can help distinguish true infection from prey-based cryptosporidia seen in fecal samples.

Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient's circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women's cancer.

Prognostic Value of Preoperative Imaging: Comparing 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography to Computed Tomography Alone for Preoperative Planning in High-risk Histology Endometrial Carcinoma.

OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) increases the sensitivity for preoperative detection of lymph nodes and distant metastases in endometrial cancer. The objective of this investigation was to determine the prognostic value of preoperative PET-CT compared with computed tomography (CT) alone for high-risk endometrial carcinoma. MATERIALS AND METHODS: We performed a retrospective review of high-risk histology endometrial cancer from 2008 to 2015. Clinical variables including surgical procedure, preoperative imaging modality, and outcome were collected. Survival analysis was performed utilizing the Kaplan-Meier and Cox proportional hazards methodologies. RESULTS: Of the 555 women treated for high-risk histology endometrial cancer, 88 (16%) had preoperative PET-CT, and 97 (17%) CT without PET available. PET-CT demonstrated positive findings in 37 women (42%) compared with 33 (30%) with preoperative CT alone. PET-CT had a positive predictive value of 96% for nodal metastasis compared with 60% for CT alone. The median follow-up time for the entire cohort was 59 months (range, 12 to 96 mo). Patients with a negative preoperative PET-CT (n=54) had a median progression-free survival (PFS) that was not reached, whereas the median PFS in the PET-CT positive group was 13 months (n=34). Women with a negative PET-CT had a longer median overall survival (OS) not yet reached compared with 34 months in the PET-CT positive cohort (hazard ratio, 2.4; P<0.001). CT findings did not associate with PFS or OS. CONCLUSIONS: PET-CT demonstrated superior sensitivity for lymph node metastasis and detecting distant disease compared with CT. Preoperative PET-CT, whether positive or negative, offered OS and PFS prognostic value not observed with CT alone.

Colonic obstruction in three captive reticulated giraffe (Giraffa camelopardalis reticulata).

Fatal colonic obstructions were diagnosed in three captive, adult, reticulated giraffe (Giraffa camelopardalis reticulata). Clinical presentations varied, but all cases displayed decreased activity, anorexia, and considerably decreased fecal production, consistent with intestinal obstruction. Case 1 was diagnosed at necropsy with a phytobezoar obstructing the spiral colon. Case 2 was diagnosed at necropsy with a fecal impaction of the colon. Case 3 was diagnosed during surgery with colonic ileus. Cases 2 and 3 underwent surgical intervention but were markedly compromised by the time of surgery and died during surgery or 24 hr postoperatively. Gastrointestinal obstruction, requiring aggressive supportive care and early surgical intervention, should be considered in giraffe in which anorexia and substantially decreased fecal production are observed. Abdominal exploratory surgery will likely be necessary for diagnosis and treatment. Based on a small number of cases, gastrointestinal obstruction has a poor prognosis in giraffe.

Diagnostic imaging in terrestrial invertebrates: Madagascar hissing cockroach (Gromphadorhina portentosa), desert millipede (Orthoporus sp.), emperor scorpion (Pandinus imperator), Chilean rosehair tarantula (Grammostola spatulata), Mexican fireleg tarantula (Brachypelma boehmei), and Mexican redknee tarantula (Brachypelma smithi).

Limited veterinary information is available for invertebrates. The purpose of this study was to improve baseline knowledge of invertebrate radiology and radiographic anatomy by evaluating diagnostic imaging modalities in six terrestrial invertebrate species. For each species, variably sized individuals were radiographed using multiple techniques to obtain optimal images, and radiographic technique charts were formulated using this data. To evaluate anatomy and compare gastrointestinal transit information among carnivores, omnivores, and herbivores, gastrointestinal contrast radiography was employed. Individuals were fed radiographic contrast media or contrast-containing food items. Contrast radiography resulted in improved visualization of gastrointestinal anatomy in all species. Radiographic contrast media was visualized in gastrointestinal tracts in at least one individual of all taxa for greater than 60 days, substantially longer than expected. Survey and gastrointestinal contrast radiographs of cockroaches were superior to those studies in other species. Zoo Biol 27:109-125, 2008. (c) 2008 Wiley-Liss, Inc.

West Nile virus seroconversion in penguins after vaccination with a killed virus vaccine or a DNA vaccine.

To investigate the serologic response of penguins to West Nile virus (WNV) vaccines, four species of exclusively indoor-housed penguins, negative for WNV by serology, were evaluated: Humboldt (Spheniscus humboldti), Magellanic (Spheniscus magellanicus), Gentoo (Pygoscelis papua), and Rockhopper (Eudyptes chrysoscome) penguins. Birds were inoculated with either a killed virus vaccine or a plasmid-mediated DNA WNV vaccine, and postinoculation serology was evaluated. Both vaccines induced seroconversion in all four species, and no adverse reactions were noted. Postvaccination serology results varied across species and vaccine types. However, in all four species, the killed virus vaccine resulted in a greater seroconversion rate than the DNA vaccine and in a significantly shorter time period. Additionally, the duration of the seropositive titer was significantly longer in those birds vaccinated with the killed virus vaccine compared with those vaccinated with the DNA vaccine. A subset of unvaccinated penguins serving as negative controls remained negative throughout the duration of the study despite the presence of WNV in the geographic locations of the study, suggesting that indoor housing may minimize exposure to the virus and may be an additional means of preventing WNV infection in penguins.

Fatal disseminated encephalitozoonosis in a captive, adult Goeldi's monkey (Callimico goeldii) and subsequent serosurvey of the exposed conspecifics.

A captive, adult male Goeldi's monkey (Callimico goeldii) (GM) presented in acute respiratory distress 4 yr after importation into the United States from Europe. Radiographs and echocardiogram were consistent with heart failure. The monkey died within 24 hr of presentation. Necropsy findings included multicentric arteritis and aortitis with aneurysm associated with microsporidian organisms morphologically consistent with Encephalitozoon species. Polymerase chain reaction confirmed organisms were Encephalitozoon cuniculi. Sequence analysis of amplicons generated by using primers specific for the polar tube protein of E. cuniculi determined the organism to be genotype II. An E. cuniculi serosurvey of potentially exposed conspecifics that represented approximately 40% of the captive GM population in the United States was conducted. Multiple individuals that had been imported from Europe with the individual of this report were seropositive via an immunofluorescent antibody assay for E. cuniculi. Multiple samples were available from 3 individuals that demonstrated a decrease in titer or reversion to seronegative status within 3 yr of initial positive status. All other GM were negative on serology. This case is unique in that the genotype identified (genotype II) was different than the genotype (genotype III) reported in other New World primate (NWP) species, the patterns of arteritis were different from the typical pattern of microsporidial vasculitis described in other species, and clinical disease was observed in an adult. Most reported cases of clinical disease secondary to E. cuniculi in NWP have been in neonates and juveniles.

Combined Oocyte Retrieval and Robot-assisted Hysterectomy in a Super Morbidly Obese Patient with Endometrial Carcinoma.

AIM: To report on the unique, innovative management of a super morbidly obese patient presenting for fertility preservation in the setting of Grade 2 endometrioid endometrial adenocarcinoma. CASE REPORT: A back-to-back oocyte retrieval and robot-assisted total laparoscopic hysterectomy (RA-TLH) with bilateral salpingo-oophorectomy (BSO) was performed in a 37-year-old nulligravid woman with super morbid obesity (BMI 63 kg/m2) with endometrial cancer. MAIN OUTCOME MEASURE: the successful retrieval of oocytes for fertility preservation and oncologic intervention via RA-TLH with BSO in the same operative and anesthetic episode. RESULTS: This combined procedure strategy was successful in our case and is a feasible option for similar high-risk patients in the future. CONCLUSION: Identifying safe and effective approaches for oocyte retrieval in morbidly obese patients represents a pressing need as obesity rates rise among reproductive-aged women. Back-to-back oocyte retrieval and RA-TLH with BSO are not only feasible, but could also decrease significant anesthetic risks for morbidly obese patients.

Human Papillomavirus and Its Testing Assays, Cervical Cancer Screening, and Vaccination.

Human papillomavirus (HPV) was found to be the causative agent for cervical cancer in the 1980s with almost 100% of cervical cancer cases testing positive for HPV. Since then, many studies have been conducted to elucidate the molecular basis of HPV, the mechanisms of carcinogenesis of the virus, and the risk factors for HPV infection. Traditionally, the Papanicolaou test was the primary screening method for cervical cancer. Because of the discovery and evolving understanding of the role of HPV in cervical dysplasia, HPV testing has been recommended as a new method for cervical cancer screening by major professional organizations including the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology. In order to detect HPV infections, many sensitive and specific HPV assays have been developed and used clinically. Different HPV assays with various principles have shown their unique advantages and limitations. In response to a clear causative relationship between high-risk HPV and cervical cancer, HPV vaccines have been developed which utilize virus-like particles to create an antibody response for the prevention of HPV infection. The vaccines have been shown in long-term follow-up studies to be effective for up to 8 years; however, how this may impact screening for vaccinated women remains uncertain. In this chapter, we will review the molecular basis of HPV, its pathogenesis, and the epidemiology of HPV infection and associated cervical cancer, discuss the methods of currently available HPV testing assays as well as recent guidelines for HPV screening, and introduce HPV vaccines as well as their impact on cervical cancer screening and treatments.

Epigenetic remodeling regulates transcriptional changes between ovarian cancer and benign precursors.

Regulation of lineage-restricted transcription factors has been shown to influence malignant transformation in several types of cancer. Whether similar mechanisms are involved in ovarian cancer pathogenesis is unknown. PAX8 is a nuclear transcription factor that controls the embryologic development of the Müllerian system, including the fallopian tubes. Recent studies have shown that fallopian tube secretory epithelial cells (FTSECs) give rise to the most common form of ovarian cancer, high-grade serous ovarian carcinomas (HGSOCs). We designed the present study in order to understand whether changes in gene expression between FTSECs and HGSOCs relate to alterations in PAX8 binding to chromatin. Using whole transcriptome shotgun sequencing (RNA-Seq) after PAX8 knockdown and ChIP-Seq, we show that FTSECs and HGSOCs are distinguished by marked reprogramming of the PAX8 cistrome. Genes that are significantly altered between FTSECs and HGSOCs are enriched near PAX8 binding sites. These sites are also near TEAD binding sites, and these transcriptional changes may be related to PAX8 interactions with the TEAD/YAP1 signaling pathway. These data suggest that transcriptional changes after transformation in ovarian cancer are closely related to epigenetic remodeling in lineage-specific transcription factors.