Hands off the Mink! Using Environmental Sampling for SARS-CoV-2 Surveillance in American Mink.

Throughout the COVID-19 pandemic, numerous non-human species were shown to be susceptible to natural infection by SARS-CoV-2, including farmed American mink. Once infected, American mink can transfer the virus from mink to human and mink to mink, resulting in a high rate of viral mutation. Therefore, outbreak surveillance on American mink farms is imperative for both mink and human health. Historically, disease surveillance on mink farms has consisted of a combination of mortality and live animal sampling; however, these methodologies have significant limitations. This study compared PCR testing of both deceased and live animal samples to environmental samples on an active outbreak premise, to determine the utility of environmental sampling. Environmental sampling mirrored trends in both deceased and live animal sampling in terms of percent positivity and appeared more sensitive in some low-prevalence instances. PCR CT values of environmental samples were significantly different from live animal samples' CT values and were consistently high (mean CT = 36.2), likely indicating a low amount of viral RNA in the samples. There is compelling evidence in favour of environmental sampling for the purpose of disease surveillance, specifically as an early warning tool for SARS-CoV-2; however, further work is needed to ultimately determine whether environmental samples are viable sources for molecular epidemiology investigations.

Leucocyte profiles of Arctic marine birds: correlates of migration and breeding phenology.

Most Arctic marine birds are migratory, wintering south of the limit of annual pack ice and returning north each year for the physiologically stressful breeding season. The Arctic environment is changing rapidly due to global warming and anthropogenic activities, which may influence the timing of breeding in relation to arrival times following migration, as well as providing additional stressors (e.g. disturbance from ships) to which birds may respond. During stressful parts of their annual cycle, such as breeding, birds may reallocate resources so that they have increased heterophil-to-lymphocyte ratios in their white blood cell (leucocyte) profiles. We analysed leucocyte profiles of nine species of marine birds to establish reference ranges for these species in advance of future Arctic change. Leucocyte profiles tended to cluster among taxonomic groups across studies, suggesting that reference values for a particular group can be established, and within species there was evidence that birds from colonies that had to migrate farther had higher heterophil-to-lymphocyte ratios during incubation than those that did not have to travel as far, particularly for species with high wing loading.

Maternal development experiences of women hospitalized to prevent preterm birth.

OBJECTIVE: To examine ways that women's experience of hospitalization with bed rest to prevent preterm birth impacts prenatal maternal development. METHOD: Interviews based on the Interview Schedules for Dimensions of Maternal Development in Psychosocial Adaptation to Pregnancy were conducted at a hospital in the southwestern United States with a convenience sample of 41 women during confinement to bed rest to prevent preterm birth. The interviews were recorded, and verbatim transcripts were submitted to thematic analysis. RESULTS: Five themes were mapped from the women's narratives: (1) acceptance of pregnancy, but with fears specific to elevated risks to self and baby; (2) heightened identification with motherhood and fatherhood protector roles; (3) renewal or deepening of mother-daughter closeness intensified by high-risk pregnancy; (4) enhanced couple support and collaboration; and (5) acceptance of responsibility to perform in remaining pregnant and preparing for labor, but willingness to accept help from doctors and nurses. CONCLUSIONS: This study of hospitalization to prevent preterm birth showed that women experience hospitalization as a burden to be endured to meet future goals, but that it also can facilitate prenatal maternal development in psychosocial adaptation to high risk pregnancy. Implications for research and practice are discussed.

NUP98-HOXA9-transgenic zebrafish develop a myeloproliferative neoplasm and provide new insight into mechanisms of myeloid leukaemogenesis.

NUP98-HOXA9 [t(7;11) (p15;p15)] is associated with inferior prognosis in de novo and treatment-related acute myeloid leukaemia (AML) and contributes to blast crisis in chronic myeloid leukaemia (CML). We have engineered an inducible transgenic zebrafish harbouring human NUP98-HOXA9 under the zebrafish spi1(pu.1) promoter. NUP98-HOXA9 perturbed zebrafish embryonic haematopoiesis, with upregulated spi1 expression at the expense of gata1a. Markers associated with more differentiated myeloid cells, lcp1, lyz, and mpx were also elevated, but to a lesser extent than spi1, suggesting differentiation of early myeloid progenitors may be impaired by NUP98-HOXA9. Following irradiation, NUP98-HOXA9-expressing embryos showed increased numbers of cells in G2-M transition compared to controls and absence of a normal apoptotic response, which may result from an upregulation of bcl2. These data suggest NUP98-HOXA9-induced oncogenesis may result from a combination of defects in haematopoiesis and an aberrant response to DNA damage. Importantly, 23% of adult NUP98-HOXA9-transgenic fish developed a myeloproliferative neoplasm (MPN) at 19-23 months of age. In summary, we have identified an embryonic haematopoietic phenotype in a transgenic zebrafish line that subsequently develops MPN. This tool provides a unique opportunity for high-throughput in vivo chemical modifier screens to identify novel therapeutic agents in high risk AML.

Impacts of frequent, acute pulses of corticosterone on condition and behavior of Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii).

Little is known about how frequent, acute stressors affect wild animals. We present two experiments conducted on captive, Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii) that explore how frequent, acute doses of corticosterone (CORT) affect condition and behavior. CORT was administered either once or three times a day to birds in pre-breeding, early-breeding, or late-breeding life-history stages. Two additional groups were included to control for the CORT delivery vehicle, DMSO, and the treatment process. Our results indicate that CORT treatment decreases condition, but that its effects are dependent on frequency and life stage. Specifically, CORT-treated birds delayed the onset of molt and had reduced body mass, flight muscle, and food consumption. CORT treatment did not affect fat stores, bile retention in the gallbladder, or the expression of migratory restlessness behavior. These results increase our understanding of the effects of frequent, acute stressors and the development of chronic stress states.

Effects of repeated, short-term, corticosterone administration on the hypothalamo-pituitary-adrenal axis of the white-crowned sparrow (Zonotrichia leucophrys gambelii).

Our knowledge of glucocorticoid actions in vertebrates comes primarily from laboratory studies, which are often conducted with little consideration of how animals experience changes in glucocorticoid secretion in natural contexts. Typically, free-living animals are exposed to acute perturbations of the environment, ranging from a few minutes to a few hours duration, with varying frequency. The cumulative effects of these perturbations and their resultant glucocorticoid surges are not well known. To investigate the possible cumulative effects of repeated, acute surges in glucocorticoid secretion, we developed an ecologically relevant methodology for treating captive white-crowned sparrows (Zonotrichia leucophrys gambelii) with corticosterone (CORT). We dissolved CORT in dimethylsulfoxide (DMSO) and administered this cocktail directly on the skin. Treatments resulted in small elevations of CORT within the physiological range. In our first experiment at the end of the breeding life stage, birds were treated three times a day (3x). Two control groups were used: one treated with DMSO 3x and one not handled nor treated. In a second study at the beginning of the breeding life stage, one group was treated once a day and a second group 3x. A DMSO-control group was used for each dosage regime. Repeated, acute administration of CORT resulted in higher baseline CORT levels and a down-regulation of the endogenous adrenocortical response to a standardized stress. Maximum CORT and plasma corticosterone binding globulin levels increased in response to the CORT treatments only at the end of the breeding season. CORT treatment did not alter adrenal size, adrenal response to ACTH, or hepatic CORT metabolism.

Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease.

BACKGROUND: Fabry disease (FD) is caused by an X-linked deficiency in the activity of alpha-galactosidase A and the resultant accumulation of globotriaosylceramide (Gb3) in multiple tissues. Nearly all classically affected males with FD experience kidney dysfunction, with progression to end-stage renal disease (ESRD) in the third decade of life or shortly thereafter. METHODS: Twenty-two FD patients (20 men and 2 women) receiving dialysis or who had a history of kidney transplantation were treated with agalsidase alfa in an open label setting using the same dosing regimen given to patients without ESRD (0.2 mg/kg every other week). Pharmacokinetics (PK) were determined during and following the initial dose, and safety was evaluated during therapy. Change in plasma Gb3 level was used as a surrogate marker of enzyme activity in vivo. RESULTS: A typical biphasic plasma elimination profile was seen in both dialysis and transplant patients, similar to that observed in 18 non-ESRD FD patients. Calculated PK parameters were similar to the three patient groups. In the male patients, plasma Gb3 level declined by 43% after 6 months (P<0.001). Infusion reactions were experienced by 8 of 21 (38%) patients, but did not result in any infusions being stopped prematurely. Anti-agalsidase alfa IgG antibodies were detected in 15.8% of males and 0% female patients. No anti-agalsidase alfa IgE antibodies were detected. CONCLUSIONS: The same dosing regimen of agalsidase alfa may be safely administered to FD patients with ESRD as given to those without ESRD.

AGTR2 mutations in X-linked mental retardation.

Two angiotensin II (Ang II)-specific receptors, AGTR1 and AGTR2, are expressed in the mammalian brain. Ang II actions on blood pressure regulation, water electrolyte balance, and hormone secretion are primarily mediated by AGTR1. The function of AGTR2 remains unclear. Here, we show that expression of the AGTR2 gene was absent in a female patient with mental retardation (MR) who had a balanced X;7 chromosomal translocation. Additionally, 8 of 590 unrelated male patients with MR were found to have sequence changes in the AGTR2 gene, including one frameshift and three missense mutations. These findings indicate a role for AGTR2 in brain development and cognitive function.