Pathogenicity of an emergent, ovine abortifacient Campylobacter jejuni clone orally inoculated into pregnant guinea pigs

Objective—To compare pathogenicity of an emergent abortifacient Campylobacter jejuni (IA 3902) with that of reference strains after oral inoculation in pregnant guinea pigs. Animals—58 pregnant guinea pigs. Procedures—12 animals were challenged IP with C jejuni IA 3902 along with 5 sham-inoculated control animals to confirm abortifacient potential. Once pathogenicity was confirmed, challenge via oral inoculation was performed whereby 12 guinea pigs received IA 3902, 12 received C jejuni isolated from ovine feces (OF48), 12 received a fully sequenced human C jejuni isolate (NCTC 11168), and 5 were sham-inoculated control animals. After abortions, guinea pigs were euthanized; samples were collected for microbial culture, histologic examination, and immunohistochemical analysis. Results—C jejuni IA 3902 induced abortion in all 12 animals following IP inoculation and 6 of 10 animals challenged orally. All 3 isolates colonized the intestines after oral inoculation, but only IA 3902 induced abortion. Evidence of infection existed for both IA 3902 and NCTC 11168; however, C jejuni was only recovered from fetoplacental units of animals inoculated with IA 3902. Immunohistochemical analysis localized C jejuni IA 3902 infection to subplacental trophoblasts, perivascular tissues, and phagocytes in the placental transitional zone. Conclusions and Clinical Relevance—This study revealed that C jejuni IA 3902 was a unique, highly abortifacient strain with the ability to colonize the intestines, induce systemic infection, and cause abortion because of its affinity for the fetoplacental unit. Guinea pigs could be effectively used in the study of septic abortion after oral inoculation with this Campylobacter strain

RNAseq Reveals Complex Response of Campylobacter jejuni to Ovine Bile and In vivo Gallbladder Environment

Colonization of the gallbladder by enteric pathogens such as Salmonella typhi, Listeria monocytogenes, and Campylobacter jejuni is thought to play a key role in transmission and persistence of these important zoonotic agents; however, little is known about the molecular mechanisms that allow for bacterial survival within this harsh environment. Recently, a highly virulent C. jejuni sheep abortion (SA) clone represented by the clinical isolate IA3902 has emerged as the dominant cause for sheep abortion in the United States. Previous studies have indicated that the C. jejuni clone SA can frequently be isolated from the gallbladders of otherwise healthy sheep, suggesting that the gallbladder may serve as an important reservoir for infection. To begin to understand the molecular mechanisms associated with survival in the host gallbladder, C. jejuni IA3902 was exposed for up to 24 h to both the natural ovine host in vivo gallbladder environment, as well as ovine bile in vitro. Following exposure, total RNA was isolated from the bile and high throughput deep sequencing of strand specific rRNA-depleted total RNA was used to characterize the transcriptome of IA3902 under these conditions. Our results demonstrated for the first time the complete transcriptome of C. jejuni IA3902 during exposure to an important host environment, the sheep gallbladder. Exposure to the host environment as compared to in vitro bile alone provided a more robust picture of the complexity of gene regulation required for survival in the host gallbladder. A subset of genes including a large number of protein coding genes as well as seven previously identified non-coding RNAs were confirmed to be differentially expressed within our data, suggesting that they may play a key role in adaptation upon exposure to these conditions. This research provides valuable insights into the molecular mechanisms that may be utilized by C. jejuni IA3902 to colonize and survive within the inhospitable gallbladder environment

Comparison of two commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs inoculated with Campylobacter jejuni

Objective—To compare efficacy of 2 commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs following IP inoculation with Campylobacter jejuni IA3902. Animals—51 female guinea pigs. Procedures—Pregnant and nonpregnant animals were randomly assigned to 1 of 4 treatment groups and administered a commercial Campylobacter vaccine labeled for prevention of campylobacteriosis in sheep via two 5-mL doses 14 days apart (vaccine A; n = 13), another labeled for prevention of campylobacteriosis via two 2-mL doses (vaccine B; 12), an experimental bacterin prepared from the challenge strain (12), or a sham vaccine (14). Ten days later, animals were challenged IP with C jejuni IA3902; 48 hours later, animals were euthanized, complete necropsy was performed, and blood and tissue samples were obtained for bacteriologic culture. Results—Administration of vaccine B or the experimental bacterin, but not vaccine A, significantly reduced 48-hour infection rates versus administration of the sham vaccine. A significantly reduced 48-hour infection rate was associated with administration of vaccine B independent of pregnancy status. Conclusions and Clinical Relevance—Administration of vaccine B significantly reduced infection in guinea pigs challenged with C jejuni IA3902, similar to a homologous bacterin. Results suggested that vaccine B or an autogenous product may be effective in controlling ovine campylobacteriosis caused by this emergent abortifacient strain. Bacteriologic culture of blood, liver, bile, and uterus in nonpregnant guinea pigs 48 hours after inoculation may be a useful screening tool for comparing efficacy of C jejuni vaccines

Autochthonous Transmission of Trypanosoma cruzi, Louisiana

Autochthonous transmission of the Chagas disease parasite, Trypanosoma cruzi, was detected in a patient in rural New Orleans, Louisiana. The patient had positive test results from 2 serologic tests and hemoculture. Fifty-six percent of 18 Triatoma sanguisuga collected from the house of the patient were positive for T. cruzi by PCR

Safety Evaluation of Lasalocid Use in Chinese Ring-Necked Pheasants (Phasianus colchicus)

Coccidiosis remains a significant threat to the welfare of game farm–reared pheasants in the United States. Although lasalocid has been demonstrated to be effective against pheasant specific coccidia, information regarding its safety in this species is lacking. The purpose of this study was to gather data on the safety of lasalocid when fed to Chinese ring-necked pheasants at one, two, and three times the recommended high dose of lasalocid used for prevention of coccidiosis in other poultry at three times the normal treatment period. Pheasant chicks (approximately 1 day-old; n  =  160) were randomly blocked by sex into four treatment groups and given their respective diets continuously for 6 wk. No significant differences were observed in overall feed consumption, weight gain, feed conversion rates, clinical pathology measurements, or tissue gross and histopathologic evaluations between controls and treatment groups associated with lasalocid administration. Based on the results of this study it appears that lasalocid fed at the recommended rate of 125 ppm is safe in Chinese ring-necked pheasants

Implementation strategies to improve statin utilization in individuals with hypercholesterolemia: A systematic review and meta-analysis

BACKGROUND: Numerous implementation strategies to improve utilization of statins in patients with hypercholesterolemia have been utilized, with varying degrees of success. The aim of this systematic review is to determine the state of evidence of implementation strategies on the uptake of statins. METHODS AND RESULTS: This systematic review identified and categorized implementation strategies, according to the Expert Recommendations for Implementing Change (ERIC) compilation, used in studies to improve statin use. We searched Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from inception to October 2018. All included studies were reported in English and had at least one strategy to promote statin uptake that could be categorized using the ERIC compilation. Data extraction was completed independently, in duplicate, and disagreements were resolved by consensus. We extracted LDL-C (concentration and target achievement), statin prescribing, and statin adherence (percentage and target achievement). A total of 258 strategies were used across 86 trials. The median number of strategies used was 3 (SD 2.2, range 1-13). Implementation strategy descriptions often did not include key defining characteristics: temporality was reported in 59%, dose in 52%, affected outcome in 9%, and justification in 6%. Thirty-one trials reported at least 1 of the 3 outcomes of interest: significantly reduced LDL-C (standardized mean difference [SMD] - 0.17, 95% CI - 0.27 to - 0.07, p = 0.0006; odds ratio [OR] 1.33, 95% CI 1.13 to 1.58, p = 0.0008), increased rates of statin prescribing (OR 2.21, 95% CI 1.60 to 3.06, p \u3c 0.0001), and improved statin adherence (SMD 0.13, 95% CI 0.06 to 0.19; p = 0.0002; OR 1.30, 95% CI 1.04 to 1.63, p = 0.023). The number of implementation strategies used per study positively influenced the efficacy outcomes. CONCLUSION: Although studies demonstrated improved statin prescribing, statin adherence, and reduced LDL-C, no single strategy or group of strategies consistently improved outcomes. TRIAL REGISTRATION: PROSPERO CRD42018114952

Ancient Lowland Maya neighborhoods: Average Nearest Neighbor analysis and kernel density models, environments, and urban scale

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method—combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups—to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization

Estrogens Can Disrupt Amphibian Mating Behavior

The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline