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Patterns of abnormal prion protein (PrP) accumulation during the course of chronic wasting disease (CWD) infection were studied and the distribution and timing of disease-associated PrP (PrP CWD ) deposition and lesions in 19 mule deer (Odocoileus hemionus) 90-785 days after oral inoculation were described. PrP CWD deposition occurred relatively rapidly and widely in lymphoid tissues, later in central and peripheral nervous tissues and sporadically in a variety of tissues and organs in terminal disease stages. Development of spongiform encephalopathy lagged behind PrP CWD deposition in the central nervous system (CNS), but occurred in the same neuroanatomical locations. PrP CWD deposition in the lymphatic and nervous systems tended to be consistent and progressive in specific organs and tissues. Locations of PrP CWD deposition were similar between deer of two PrP genotypes (225SS and 225SF), but the time course differed between genotypes: in 225SF deer, PrP CWD accumulated more slowly in lymphatic tissues than in 225SS animals, but that disparity was small in comparison to the disparity between genotypes in timing of deposition in CNS tissue. These data confirm retropharyngeal lymph node and medulla oblongata at the level of the obex as early sites of PrP CWD accumulation in mule deer with CWD. Data on the relative time frames for and genetic influences on PrP CWD accumulation may also offer insights about epidemic dynamics and potential control strategies.

i Although parvoviruses are commonly described in domestic carnivores, little is known about their biodiversity in nondomestic species. A phylogenetic analysis of VP2 gene sequences from puma, coyote, gray wolf, bobcat, raccoon, and striped skunk revealed two major groups related to either feline panleukopenia virus ("FPV-like") or canine parvovirus ("CPV-like"). Crossspecies transmission was commonplace, with multiple introductions into each host species but, with the exception of raccoons, relatively little evidence for onward transmission in nondomestic species.

Chronic wasting disease (CWD) is a prion disease of cervids that causes neurodegeneration and death. Susceptibility to prion infections, including CWD, can be dependent on the amino acid sequence of the host prion protein (PrP). Here, CWD agent obtained from a deer expressing the 96SS genotype, associated with partial resistance to CWD, was used to infect transgenic (tg) mice expressing either 96GG or 96SS deer PrP. Transgenic mice expressing 96GG deer PrP succumbed to this agent, but tg mice expressing 96SS deer PrP did not. Additional studies using inocula from 96GG deer showed no transmission to 96SS PrP mice and delayed disease in 96GS mice. Thus, 96S PrP played an inhibitory role in disease progression in tg mice.Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) or prion disease of North American cervids that causes progressive neurodegeneration and death (24,26). Disease occurs when the normal (sensitive) host prion protein (PrPsen) is converted to an abnormal, diseaseassociated, protease-resistant form (PrPres). The incidence of CWD continues to increase in wild and captive cervids of North America, most likely via direct animal-to-animal contact or exposure to CWD agent-contaminated environments. It is known that the sequence of the host prion protein gene (PRNP) can affect susceptibility to TSE diseases, including scrapie in sheep (4) and laboratory mice (2), sporadic Creutzfeldt-Jakob disease (sCJD) (1, 6, 17), variant CJD (25) and kuru (11) in humans, and CWD in cervids (23). Susceptibility to the CWD agent has been shown to correlate with specific amino acids at defined locations within the PRNP gene, including codon 96 in white-tailed deer (9,12,15,27), codons 20 and 225 in mule deer (7,27), and codon 132 in elk (5). Approximately 55% of white-tailed deer are homozygous for glycine at position 96 (96GG), ϳ35% have glycine/serine at this position (96GS), and Յ10% are serine homozygotes (96SS), depending on geographic location (9,15,27). Strong evidence exists to show that both the 96GS and 96SS genotypes are underrepresented among populations of CWD agent-infected white-tailed deer (8,9,15,27). It is unclear if the low incidence of disease in 96GS and 96SS deer reflects only resistance to a particular CWD agent strain or is in fact a protective factor provided by cervid 96S prion protein.In some situations in which TSE occurs in an animal with a previously resistant genotype or a new species, agent adaptation and selection can occur with greater efficiency in the subsequent spread to additional individuals with similar genotypes (14, 19). By analogy, in cervids, PrPres from a few CWD agent-positive 96SS individuals might adapt to become more infectious for additional 96SS deer. To test this possibility, we developed transgenic (tg) mice that express various PRNP genotypes at codon 96 to model the situation in deer. Transgenic mice that express deer PrP with glycine at position 96 (96GG) (described previously as tg33 [12,18]) expressed PrPsen at levels comparable to the ...

Background Pregnancies have been reported after endometrial ablation but there is little data regarding subsequent pregnancy outcomes.Objective To review systematically the available evidence regarding pregnancy outcomes after endometrial ablation, in order to equip physicians effectively to counsel women considering endometrial ablation.Search strategy MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were searched through January 2017.Selection criteria Published and unpublished literature in any language describing pregnancy after endometrial ablation or resection was eligible.Data collection and analysis Data about preconception characteristics and pregnancy outcomes were extracted and analysed according to study design of source and pregnancy viability.Main results We identified 274 pregnancies from 99 sources; 78 sources were case reports. Women aged 26-50 years (mean 37.5 AE 5 years) conceived a median of 1.5 years after ablation (range: 3 weeks prior to 13 years after). When reported, 80-90% had not used contraception. In all, 85% of pregnancies from trial/ observational studies ended in termination, miscarriage or ectopic pregnancy. Pregnancies that continued (case report and non-case report sources) had high rates of preterm delivery, caesarean delivery, caesarean hysterectomy, and morbidly adherent placenta. Case reports also frequently described preterm premature rupture of membranes, intrauterine growth restriction, intrauterine fetal demise, uterine rupture, and neonatal demise.Conclusions An unexpectedly high rate of pregnancy complications is reported in the available literature (which may reflect publication bias) and high-quality evidence is lacking. However, based on the existing evidence, women undergoing endometrial ablation should be informed that subsequent pregnancy may have serious complications and should be counselled to use reliable contraception after the procedure.

We compared mule deer (Odocoileus hemionus) of two different PRNP genotypes (225SS, 225FF) for susceptibility to chronic wasting disease (CWD) in the face of environmental exposure to infectivity. All three 225SS deer had immunohistochemistry (IHC)-positive tonsil biopsies by 710 days postexposure (dpe), developed classic clinical signs by 723-1,200 dpe, and showed gross and microscopic pathology, enzyme-linked immunosorbent assay (ELISA) results, and IHC staining typical of prion disease in mule deer. In contrast, although all three 225FF deer also became infected, the two individuals surviving >720 dpe had consistently negative biopsies, developed more-subtle clinical signs of CWD, and died 924 or 1,783 dpe. The 225FF deer were "suspect" by ELISA postmortem but showed negative or equivocal IHC staining of lymphoid tissues; both clinically affected 225FF deer had spongiform encephalopathy in the absence of IHC staining in the brain tissue. The experimental cases resembled three cases encountered among five additional captive 225FF deer that were not part of our experiment but also died from CWD. Aside from differences in clinical disease presentation and detection, 225FF mule deer also showed other, more-subtle, atypical traits that may help to explain the rarity of this genotype in natural populations, even in the presence of enzootic CWD.

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These results suggest nonoccupational exposures to TCDD or other factors while in SEA may contribute to cancer risk in these veterans.