Molecular Inferences Suggest Multiple Host Shifts of Rabies Viruses from Bats to Mesocarnivores in Arizona during 2001–2009

In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001–2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T242 in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other approaches

Emerging Pattern of Rabies Deaths and Increased Viral Infectivity

Most human rabies deaths in the United States can be attributed to unrecognized exposures to rabies viruses associated with bats, particularly those associated with two infrequently encountered bat species (Lasionycteris noctivagans and Pipistrellus subflavus). These human rabies cases tend to cluster in the southeastern and northwestern United States. In these regions, most rabies deaths associated with bats in nonhuman terrestrial mammals are also associated with virus variants specific to these two bat species rather than more common bat species; outside of these regions, more common bat rabies viruses contribute to most transmissions. The preponderance of rabies deaths connected with the two uncommon L. noctivagans and P. subflavus bat rabies viruses is best explained by their evolution of increased viral infectivity

Novel Lyssaviruses Isolated from Bats in Russia

Two new rabies-related viruses were discovered in Russia during 2002. Viruses were isolated from bats in Eastern Siberia near Baikal Lake and in the western Caucasus Mountains. After preliminary antigenic and genetic characterization, we found that both viruses should be considered as new putative lyssavirus genotypes

Human Rabies: A Reemerging Disease in Costa Rica?

Two human rabies cases caused by a bat-associated virus variant were identified in September 2001 in Costa Rica, after a 31-year absence of the disease in persons. Both patients lived in a rural area where cattle had a high risk for bat bites, but neither person had a definitive history of being bitten by a rabid animal. Characterization of the rabies viruses from the patients showed that the reservoir was the hematophagous Vampire Bat, Desmodus rotundus, and that a sick cat was the vector

Investigating the relationship between competence and patient outcome with CBT

Little is understood about the relationship between therapist competence and the outcome of patients treated for common mental health disorders. Understanding the relationship between competence and patient outcome is of fundamental importance to the dissemination and implementation of Cognitive Behavioural Therapy (CBT). The current study extends existing literature by exploring the relationship between CBT competence and patient outcome in routine clinical practice within the framework of the British Government’s Improving Access to Psychological Therapies (IAPT) programme. Participants comprised 43 therapists treating 1247 patients over a training period of one year. Results found little support of a general association between CBT competence and patient outcome; however significantly more patients of the most competent therapists demonstrated a reliable improvement in their symptoms of anxiety than would be expected by chance alone, and fewer experienced no reliable change. Conversely, significantly more patients treated by the least competent therapists experienced a reliable deterioration in their symptoms than would be expected. The implications of these results for the dissemination and implementation of CBT are discussed

Enzootic Rabies Elimination from Dogs and Reemergence in Wild Terrestrial Carnivores, United States

Independent enzootics in wild terrestrial carnivores resulted from spillover events from long-term enzootics associated with dogs

Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue

PURPOSE: Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. METHODS: We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. RESULTS: Fourteen percent of evaluated SNPs (8 SNPs) were associated with TDLU counts at p<0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50% that were either significantly or nonsignficantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among 10 SNPs that were statistically significantly associated with at least one TDLU involution measure (p<0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. CONCLUSIONS: Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results