Extreme plasticity of reproductive state in a female rodent.

Successful sexual reproduction relies on the coordination of multiple biological systems, yet traditional concepts of biological sex often ignore the natural plasticity in morphology and physiology underlying sex. Most female mammals develop a patent (i.e., opened) vaginal entrance (introitus) prenatally or postnatally before or during puberty, usually under the influence of estrogens, and remain patent for the remainder of their lifespan1. An exception is the southern African giant pouched rat (Cricetomys ansorgei), whose vaginal introitus remains sealed well into adulthood2. Here, we explore this phenomenon and report that the reproductive organs and the vaginal introitus can undergo astounding and reversible transformation. Non-patency is characterized by reduced uterine size and the presence of a sealed vaginal introitus. Furthermore, the female urine metabolome shows that patent and non-patent females profoundly differ in their urine content, a reflection of differences in physiology and metabolism. Surprisingly, patency state did not predict fecal estradiol or progesterone metabolite concentrations. Exploring the plasticity that exists in reproductive anatomy and physiology can uncover that traits long considered 'fixed' in adulthood can become plastic under specific evolutionary pressures. Moreover, the barriers to reproduction that such plasticity creates present unique challenges to maximizing reproductive potential.

Use of Fluconazole-impregnated Beads to Treat Osteomyelitis Caused by Coccidioides in a Pigtailed Macaque (Macaca nemestrina).

A 3-y-old male pigtailed macaque (Macaca nemestrina) presented for swelling of the left distal forearm and decreased use of the arm. The monkey had been raised at an indoor-outdoor facility in Arizona and transferred to an indoor facility in Washington 2 mo prior to presentation. A preliminary diagnosis of fungal osteomyelitis of the radius was made based on radiographs and Coccidioides titers. In addition to systemic antifungal treatment, surgery was performed to debride the bony lesion and implant polymethylmethacrylate beads impregnanted with the anti-fungal fluconazole. Histologic examination of the debrided material confirmed the diagnosis of fungal osteomyelitis. The surgical procedure resulted in clinical improvement, as evidenced by weight gain and decreased Coccidioides titers. The beads were removed in a second surgery, and the bony lesion completely resolved. With continued systemic fluconazole treatment, the monkey remained healthy with no further evidence of osteomyelitis. Coccidioides is an emerging pathogen that causes significant morbidity and mortality in both humans and animals. Bone infections can be resistant to systemic treatment, and the implantation of fluconazoleimpregnated beads may offer a successful treatment strategy for fungal osteomyelitis.

Hematologic and Biochemical Reference Intervals and Urinary Test Results for Wild-caught Adult Southern Giant Pouched Rats (Cricetomys ansorgei).

Southern giant pouched rats (Cricetomys ansorgei) are muroid rodents native to subSaharan Africa. They are increasingly used as service animals because of their keen sense of smell and are primarily known for clearing minefields in Africa. The objectives of this study were to determine hematologic and biochemical reference intervals from clinically healthy wild-caught captive adult rats, to describe the cytochemical staining reactions of peripheral blood leukocytes, and to document urinalysis findings. Blood samples were collected from the coccygeal artery of 60 isoflurane-anesthetized rats (36 males and 24 females) and analyzed with automated hematologic and biochemical analyzers; manual differential cell counts were performed on modified Wright-stained blood smears. Urine was collected by cystocentesis, and dipsticks were analyzed on a urine analyzer, with visual examination of unstained sediments. Samples from a male rat with chronic renal disease were excluded from analysis. Reference intervals were determined according to guidelines established by the American Society of Veterinary Clinical Pathology. Lymphocytes were the dominant leukocyte in peripheral blood and granular lymphocytes were identified in most animals. Male rats had significantly higher RBC, absolute reticulocyte counts, and MCV than did female rats. Minor sex-associated differences in urea nitrogen concentration and GGT activity were noted. Leukocytes showed unique cytochemical staining characteristics. Small amounts of protein and bilirubin were found in the urine of rats of both sexes and of female rats, respectively, particularly in concentrated urine. These results will provide benchmarks for determining health status and identifying disease in this species of rat.

Recrudescence of Natural Coccidioidomycosis During Combination Antiretroviral Therapy in a Pigtail Macaque Experimentally Infected with Simian Immunodeficiency Virus.

Coccidioidomycosis is a common fungal infection in people living with HIV-1, particularly in southwest regions of the United States where the Coccidioides sp. is endemic, but rates of infection have significantly declined in the era of potent combination antiretroviral therapy (cART). Natural coccidioidomycosis also occurs in outdoor-housed macaques residing in the southwestern states that are utilized in biomedical research. Here, we report on a recrudescent case of previously treated, naturally occurring coccidioidomycosis in a pigtail macaque that was experimentally infected with simian immunodeficiency virus (SIV) and virally suppressed on cART. Coccidioides IgG antibody titer became detectable before discontinuation of cART, but symptomatic coccidioidomycosis developed subsequent to cART withdrawal. This animal was screened and treated in accordance with the guidelines for the prevention and treatment of coccidioidomycosis, suggesting that macaques with a history of coccidioidomycosis should be excluded from enrollment in HIV studies. Continual monitoring for known endemic pathogens based on the colony of origin is also recommended for animals utilized for HIV/AIDS research.

Radiological Findings on Structural Magnetic Resonance Imaging in Fetal Alcohol Spectrum Disorders and Healthy Controls.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and cognitive impairments stemming from prenatal alcohol exposure (PAE). Although case studies have demonstrated striking visible brain abnormalities in humans (enlargement of the lateral ventricles, thinning or absence of the corpus callosum, etc.), few studies have systematically determined how these radiological findings generalize to the wider population of individuals living with FASD. METHODS: This study examines rates of structural brain anomalies on magnetic resonance imaging (MRI) as determined by 2 radiologists in a retrospective blinded review of 163 controls and 164 individuals with PAE who were previously scanned as participants of past research studies. Incidental findings were categorized as normal variants, nonclinically significant incidental findings, or clinically significant incidental findings. Rates were compared between diagnostic subgroups using chi-square analysis. RESULTS: There was no significant difference in the overall rate of incidental findings between groups: 75% of controls and 73% of PAE participants had no incidental findings of any kind, and only 1% of controls and 3% of PAE participants had incidental finding of clinical significance (the remaining findings were considered nonsignificant anomalies or normal variants). When the PAE group was split by diagnosis, low-lying cerebellar tonsils, polymicrogyria, and ventricular asymmetry/enlargement were all most prevalent in subjects with fetal alcohol syndrome/partial fetal alcohol syndrome. In addition, the overall rate of incidental findings was higher (41%) in participants with FAS/pFAS, compared to 25% in controls. No participants in this relatively large sample had corpus callosum agenesis. CONCLUSIONS: Although advanced quantitative MRI research has uncovered a range of differences in brain structure associated with FASD, this qualitative radiological study suggests that routine clinical MRI does not reveal a consistent pattern of brain abnormalities that can be used diagnostically in this population.

Chew on This: Emergency Imaging of the Oral Cavity and Salivary Glands-What the Clinician Really Needs to Know.

Nontraumatic emergencies of the oral cavity, sublingual and submandibular spaces, and salivary glands are common and those requiring imaging will most often be infectious in nature.1,2 However, noninfectious pathologies such as sialolithiasis, autoimmune sialoadenitis, and soft tissue swelling due to angioedema or hemorrhage are also important conditions that radiologists must be familiar with in order to inform the clinician of critical imaging findings that can have a profound impact on patient outcomes. To understand these pathologies, familiarity with the anatomy of these spaces is essential.

Full Activation Profiles and Integrity of Corticospinal Pathways in Adults With Bilateral Spastic Cerebral Palsy.

BACKGROUND: Dysfunction of corticospinal pathways has been implicated in motor impairments in people with bilateral spastic cerebral palsy (CP). While structural damage to corticospinal pathways in people with CP is known, its impact on the activation of these pathways is not. OBJECTIVE: To provide the first, complete activation profile of corticospinal pathways in adults with CP using a full range of transcranial magnetic stimulation (TMS) intensities and voluntary contractions. METHODS: TMS targeted the soleus muscle of 16 adults with bilateral spastic CP and 15 neurologically intact (NI) control participants. Activation profiles were generated using motor-evoked potentials (MEPs) produced by varying both stimulation intensity and degree of voluntary muscle activity. Anatomical integrity of corticospinal pathways was also measured with diffusion tractography. RESULTS: Participants with CP had smaller MEPs produced by TMS at 1.2× active motor threshold during submaximal (20%) muscle activity and smaller maximal MEPs produced under any combination of stimulation intensity and voluntary muscle activity. At a fixed stimulation intensity, increasing voluntary muscle activity facilitated MEP amplitudes to a lesser degree in the participants with CP. Consistent differences in diffusion tractography suggested structural abnormalities in the corticospinal pathways of participants with CP that correlated with maximal MEPs. CONCLUSION: People with bilateral spastic CP have impaired activation of low and high-threshold corticospinal pathways to soleus motoneurons by TMS and reduced facilitation by voluntary activity that may be associated with structural damage to these pathways. These impairments likely contribute to impaired voluntary movement.

High-Resolution Isotropic Three-Dimensional MR Imaging of the Extraforaminal Segments of the Cranial Nerves.

High-resolution isotropic 3-dimensional (D) MR imaging with and without contrast is now routinely used for imaging evaluation of cranial nerve anatomy and pathologic conditions. The anatomic details of the extraforaminal segments are well-visualized on these techniques. A wide range of pathologic entities may cause enhancement or displacement of the nerve, which is now visible to an extent not available on standard 2D imaging. This article highlights the anatomy of extraforaminal segments of the cranial nerves and uses select cases to illustrate the utility and power of these sequences, with a focus on constructive interference in steady-state.

Preliminary validation of the Knee Inflammation MRI Scoring System (KIMRISS) for grading bone marrow lesions in osteoarthritis of the knee: data from the Osteoarthritis Initiative.

OBJECTIVE: Bone marrow lesions (BML) are an MRI feature of osteoarthritis (OA) offering a potential target for therapy. We developed the Knee Inflammation MRI Scoring System (KIMRISS) to semiquantitatively score BML with high sensitivity to small changes, and compared feasibility, reliability and responsiveness versus the established MRI Osteoarthritis Knee Score (MOAKS). METHODS: KIMRISS incorporates a web-based graphic overlay to facilitate detailed regional BML scoring. Observers scored BML by MOAKS and KIMRISS on sagittal fluid-sensitive sequences. Exercise 1 focused on interobserver reliability in Osteoarthritis Initiative observational data, with 4 readers (two experienced/two new to KIMRISS) scoring BML in 80 patients (baseline/1 year). Exercise 2 focused on responsiveness in an open-label trial of adalimumab, with 2 experienced readers scoring BML in 16 patients (baseline/12 weeks). RESULTS: Scoring time was similar for KIMRISS and MOAKS. Interobserver reliability of KIMRISS was equivalent to MOAKS for BML status (ICC=0.84 vs 0.79), but consistently better than MOAKS for change in BML: Exercise 1 (ICC 0.82 vs 0.53), Exercise 2 (ICC 0.90 vs 0.32), and in new readers (0.87-0.92 vs 0.32-0.51). KIMRISS BML was more responsive than MOAKS BML: post-treatment BML improvement in Exercise 2 reached statistical significance for KIMRISS (SRM -0.69, p=0.015), but not MOAKS (SRM -0.12, p=0.625). KIMRISS BML also more strongly correlated to WOMAC scores than MOAKS BML (r=0.80 vs 0.58, p<0.05). CONCLUSIONS: KIMRISS BML scoring was highly feasible, and was more reliable for assessment of change and more responsive to change than MOAKS BML for expert and new readers.

Metabolic tumour volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery.

BACKGROUND: Metabolic tumour volume (MTV) obtained from pre-treatment 18 F-fluorodeoxydeglucose positron emission tomography with computed tomography (PET-CT) has been validated as an independent predictive factor of outcomes in head and neck cancer patients (HNC) treated with primary chemoradiotherapy (CRT). However its role in patients treated with primary surgery has not yet been studied. OBJECTIVE: To evaluate the prognostic value of MTV in patients treated with primary surgery for oral cavity squamous cell carcinoma (OCSCC). METHOD: Demographic and survival data was obtained from patients diagnosed with OCSCC from 2008-2012 in Alberta, Canada. All patients included in the study had PET-CT scan before curative surgical resection. MTV and maximum standardized uptake value (SUVmax) value was delineated from pre-treatment PET-CT scans using Segami Oasis software (Columbus, OH). MTV and SUVmax were divided into intertertile thirds before statistical analysis to allow for in-group comparison of survival. RESULTS: A total of 80 patients were analyzed using SPSS ver. 20.0 (SPSS Inc, Chicago, IL). Five-year overall, and disease-free survival using Kaplan-Meier curves were 70% and 73% respectively. When the combined SUVmax (tumour primary and locoregional metastasis) was evaluated, it failed to predict overall (HR = 1.0, p = 0.99) or disease-free survival (HR = 1.0, p = 0.227). CONCLUSIONS: This study shows that MTV is an independent adverse prognostic factor for death and disease recurrence in OCSCC treated with primary surgery.

Effects of cardiac motion on 3D contrast-enhanced MR angiography of the carotid arteries.

PURPOSE: To determine the effect of cardiac-related carotid artery motion on the image quality of 3D contrast-enhanced MR angiography (CEMRA) in patients presenting with suspected carotid artery disease. MATERIALS AND METHODS: Twenty patients with suspected carotid artery disease underwent cardiac-gated cinematic steady-state free precession of the carotid arteries followed by standard 3D CEMRA at 1.5 T. Using postprocessing, computer programs determined the degree of vessel wall dilation and translation across the cardiac cycle from the cinematic exam and related this to vessel wall sharpness in 3D CEMRA, which was determined objectively by computer analysis and subjectively by a panel of expert neuroradiologists. RESULTS: In patients, across 40 arteries the average carotid vessel movement due to cardiac pulsation was 0.36 ± 0.17 mm and translation 1.53 ± 0.94 mm. When using computer analysis of sharpness, the mean carotid wall motion had a weak negative correlation with 3D CEMRA vessel sharpness (Pearson's correlation -0.23, P < 0.01). However, the same trend was not present from the radiological review. CONCLUSION: In standard 3D CEMRA in patients with suspected carotid artery disease, cardiac-related carotid movement was a statistically significant source of degradation in vessel sharpness, but did not appear to be clinically significant.

Cage-change interval preference in mice.

Before animal research facilities began using individually ventilated cage (IVC) systems for mice, cages were often changed one or more times per week. When using IVC systems, however, it is standard practice to change cages only once every 2-3 weeks. When deciding how often to change cages, personnel may consider the cost of labor needed to change the cage, as well as the cage type and bedding type, rather than animal preference or concern for animal well-being. The authors carried out a simple preference test in groups of mice. Mice were allowed to choose between an unsoiled cage and cages that had not been changed for 1 d, 7 d or 14 d. When evaluating where mice positioned their nests and the amount of time mice spent in the various cages, the authors found that the mice preferred the unsoiled cage. Younger mice (<150 d old) showed a stronger preference for the unsoiled cage than did older mice (>150 d old). Further studies are warranted to evaluate mice's preferences for cages changed at different intervals and to determine whether prolonging the interval between cage changes has any negative effects on mice.

Effects of transcranial direct current stimulation on the excitability of the leg motor cortex.

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA has been shown to be efficacious in increasing (via anodal tDCS) or decreasing (via cathodal tDCS) the excitability of corticospinal projections to muscles of the hand. In this study, we examined whether tDCS at currents of 2 mA could effect similar changes in the excitability of deeper cortical structures that innervate muscles of the lower leg. Similar to the hand area, 10 min of stimulation with the anode over the leg area of the motor cortex increased the excitability of corticospinal tract projections to the tibialis anterior (TA) muscle, as reflected by an increase in the amplitude of the motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation. MEP amplitudes recorded at rest and during a background contraction were increased following anodal tDCS and remained elevated at 60 min compared to baseline values by 59 and 35%, respectively. However, in contrast to the hand, hyperpolarizing cathodal stimulation at equivalent currents had minimal effect on the amplitude of the MEPs recorded at rest or during background contraction of the TA muscle. These results suggest that it is more difficult to suppress the excitability of the leg motor cortex with cathodal tDCS than the hand area of the motor cortex.