Augmenting hippocampal-prefrontal neuronal synchrony during sleep enhances memory consolidation in humans.

Memory consolidation during sleep is thought to depend on the coordinated interplay between cortical slow waves, thalamocortical sleep spindles and hippocampal ripples, but direct evidence is lacking. Here, we implemented real-time closed-loop deep brain stimulation in human prefrontal cortex during sleep and tested its effects on sleep electrophysiology and on overnight consolidation of declarative memory. Synchronizing the stimulation to the active phases of endogenous slow waves in the medial temporal lobe (MTL) enhanced sleep spindles, boosted locking of brain-wide neural spiking activity to MTL slow waves, and improved coupling between MTL ripples and thalamocortical oscillations. Furthermore, synchronized stimulation enhanced the accuracy of recognition memory. By contrast, identical stimulation without this precise time-locking was not associated with, and sometimes even degraded, these electrophysiological and behavioral effects. Notably, individual changes in memory accuracy were highly correlated with electrophysiological effects. Our results indicate that hippocampo-thalamocortical synchronization during sleep causally supports human memory consolidation.

Neurological and immunological dysfunction in two patients with Bartonella henselae bacteremia.

Recently, BAPGM enrichment culture has documented Bartonella bacteremia in previously healthy, "nonimmunocompromised" patients following arthropod exposures. Neurobartonellosis should be among the differential diagnoses for patients with persistent or recurrent neurological symptoms of undetermined etiology. Microbiological and immunological testing should be concurrently pursued to determine whether defective immune function accompanies Bartonella bacteremia.

Bartonella henselae in canine cavitary effusions: prevalence, identification, and clinical associations.

BACKGROUND: Previous reports suggest an association between Bartonella infection and effusions in dogs and human beings. OBJECTIVES: The aims of this study were to determine the prevalence of Bartonella infection in canine effusions and to investigate historic and clinical parameters predictive of Bartonella in dogs with effusions. METHODS: Canine cavitary effusions submitted for analysis and, if available, paired EDTA blood, were screened for Bartonella infection using the Bartonella α-proteobacteria growth medium enrichment culture/PCR diagnostic platform (Bartonella enrichment PCR or ePCR) at Galaxy Diagnostics, Inc. RESULTS: Bartonella henselaeDNA was PCR-amplified and sequenced from 15% (12/80) of sampled dogs. Enrichment culture prior to PCR testing was required for Bartonella detection in 92% (11/12) of cases. Twenty percent (4/20), 13% (8/60), and 0% (0/4) of dogs with pleural, peritoneal, and pericardial effusions, respectively, tested positive. Bartonella henselae was detected most frequently in the fall, and young and middle-aged dogs appeared to be overrepresented. Golden Retrievers and Yorkshire/Silky Terriers each comprised 25% of infected dogs (odds ratio 3.4 for Golden Retrievers). There was a weak association with hemorrhagic effusions. Fifty percent of Bartonella-positive dogs had hemorrhage as a component of their effusion compared to 37% of PCR-negative dogs (odds ratio 1.7). CONCLUSIONS: Viable B henselae organisms occur in pleural and peritoneal effusions of dogs; the clinical relevance of which remains unclear and may represent opportunistic infection. Associations found in this study included seasonal variation, age, breed, and site of effusion.

Bartonella henselae as a cause of acute-onset febrile illness in cats.

CASE SERIES SUMMARY: At different time points spanning 6 months, three adopted feral flea-infested cats, residing in the household of a veterinary technician, became acutely anorexic, lethargic and febrile. Enrichment blood culture/PCR using Bartonella alpha Proteobacteria growth medium (BAPGM) confirmed initial infection with the same Bartonella henselae genotype in all three cases. With the exception of anemia and neutropenia, complete blood counts, serum biochemical profiles and urinalysis results were within reference intervals. Also, tests for feline leukemia virus, feline immunodeficiency virus, Toxoplasma gondii and feline coronavirus antibodies were negative. Serial daily temperature monitoring in one case confirmed a cyclic, relapsing febrile temperature pattern during 1 month, with resolution during and after treatment with azithromycin. Bartonella henselae Western immunoblot (WB) results did not consistently correlate with BAPGM enrichment blood culture/PCR results or B henselae indirect fluorescent antibody (IFA) titers, and WB titration results were not informative for establishing antibiotic treatment failure. During the respective follow-up periods, no illnesses or additional febrile episodes were reported, despite repeat documentation of B henselae bacteremia in two cats available for follow-up (one with the same genotype and the other with a different B henselae genotype); one cat was, unfortunately, killed by dogs before follow-up testing. RELEVANCE AND NOVEL INFORMATION: We conclude that microbiological diagnosis and treatment of B henselae infection in cats can be challenging, that antibody titration results and resolution of clinical abnormalities may not correlate with a therapeutic cure, and that fever and potentially neutropenia should be differential diagnostic considerations for young cats with suspected bartonellosis.

Experimental infection of dogs with Bartonella henselae and Bartonella vinsonii subsp. berkhoffii.

The lack of a suitable infection model remains an important obstacle for the pathophysiological understanding of Bartonella spp. The following pilot study was designed to determine whether cell culture-grown Bartonella henselae SA2 and Bartonella vinsonii subsp. berkhoffii genotype III would cause persistent bacteremia in dogs. Pre-inoculation screening established that two laboratory-raised Golden retrievers were naturally-infected with Bartonella koehlerae. Despite prior infection, one dog each was inoculated subcutaneously with 5 × 10(4)B. henselae (SA2 strain) or 3 × 10(4)B. vinsonii subsp. berkhoffii genotype III. Dogs were bled weekly for serological testing and culture using Bartonella alpha proteobacteria growth medium (BAPGM) diagnostic platform. Dog 1 seroconverted to B. henselae and Dog 2 seroconverted to B. vinsonii subsp. berkhoffii genotype III. Throughout the study period, Bartonella spp. DNA was neither amplified nor isolated in ante-mortem BAPGM enrichment blood cultures. B. henselae SA2 was isolated from a postmortem bone marrow from Dog 1 and B. koehlerae DNA was amplified from postmortem lung from Dog 2 following BAPGM enrichment culture. Limitations include lack of uninfected controls, a potentially suboptimal B. vinsonii subsp. berkhoffii inoculum and a relatively short duration of study. We conclude that following intradermal infection, sequestration of Bartonella spp. in tissues may limit diagnostic detection of these bacteria in dog blood samples.

Ecological diversity of Bartonella species infection among dogs and their owner in Virginia.

Bartonella species comprise a genus of gram-negative, fastidious, intracellular bacteria that have been implicated in association with an increasing spectrum of disease manifestations in dogs and human patients. In this study, chronic canine and human disease, for which causation was not diagnostically defined, were reported by the breeder of a kennel of Doberman pinschers. In addition to other diagnostic tests, serology, polymerase chain reaction, and enrichment blood culture were used to assess the prevalence of Bartonella sp. infection in the dogs and their owner. From five dogs, Bartonella vinsonii subsp. berkhoffii genotype I, multiple Bartonella henselae strains, and a species most similar to Candidatus B. volans, a rodent-associated Bartonella sp., were amplified and sequenced from biopsy tissues, cerebrospinal fluid, or blood enrichment cultures. The owner was bacteremic with B. vinsonii subsp. berkhoffii genotype I, the same subsp. and genotype detected in one of her dogs. These results further emphasize the ecological complexity of Bartonella sp. transmission in nature.

Bartonella spp. in feral pigs, southeastern United States.

In conjunction with efforts to assess pathogen exposure in feral pigs from the southeastern United States, we amplified Bartonella henselae, B. koehlerae, and B. vinsonii subsp. berkhoffii from blood samples. Feral pigs may represent a zoonotic risk for hunters or butchers and pose a potential threat to domesticated livestock.

PCR detection of Bartonella bovis and Bartonella henselae in the blood of beef cattle.

Although an organism primarily associated with non-clinical bacteremia in domestic cattle and wild ruminants, Bartonella bovis was recently defined as a cause of bovine endocarditis. The purpose of this study was to develop a B. bovis species-specific PCR assay that could be used to confirm the molecular prevalence of Bartonella spp. infection. Blood samples from 142 cattle were tested by conventional PCR targeting the Bartonella 16S-23S intergenic spacer (ITS) region. Overall, Bartonella DNA was detected in 82.4% (117/142) of the cattle using either Bartonella genus primers or B. bovis species-specific primers. Based upon size, 115 of the 117 Bartonella genus ITS PCR amplicons were consistent with B. bovis infection, which was confirmed by PCR using B. bovis species-specific primers and by sequencing three randomly selected, appropriately sized Bartonella genus PCR amplicons. By DNA sequencing, Bartonella henselae was confirmed as the two remaining amplicons, showing sequence similarity to B. henselae URBHLIE 9 (AF312496) and B. henselae Houston 1 (NC_005956), respectively. Following pre-enrichment blood culture of 12 samples in Bartonella alpha Proteobacteria growth medium (BAPGM) B. henselae infection was found in another three cows. Four of the five cows infected with B. henselae were co-infected with B. bovis. To our knowledge this study describes the first detection of B. henselae in any large ruminant species in the world and supports the need for further investigation of prevalence and pathogenic potential of B. henselae and B. bovis in cattle.

Prevalence of Ehrlichia canis, Anaplasma platys, Babesia canis vogeli, Hepatozoon canis, Bartonella vinsonii berkhoffii, and Rickettsia spp. in dogs from Grenada.

To identify the tick-borne pathogens in dogs from Grenada, we conducted a serologic survey for Ehrlichia canis in 2004 (104 dogs) and a comprehensive serologic and molecular survey for a variety of tick-borne pathogens in 2006 (73 dogs). In 2004 and 2006, 44 and 32 dogs (42.3% and 43.8%) were seropositive for E. canis, respectively. In 2006, several tick-borne pathogens were identified by serology and PCR. DNA of E. canis, Anaplasma platys, Babesia canis vogeli, Hepatozoon canis, and Bartonella sp. were identified in 18 (24.7%), 14 (19.2%), 5 (7%), 5 (7%), and 1 (1.4%) dogs, respectively. Six (8.2%) dogs were seropositive for Bartonella vinsonii subsp. berkhoffii. All dogs were seronegative and PCR-negative for Rickettsia spp. Coinfection with two or three pathogens was observed in eight dogs. Partial 16S rRNA E. canis and A. platys sequences were identical to sequences in GenBank. Partial 18S rRNA gene sequences from the Grenadian H. canis were identical to each other and had one possible mismatch (ambiguous base) from H. canis detected from Spain and Brazil. Grenadian B. c. vogeli sequences were identical to B. c. vogeli from Brazil and Japan. All of the detected pathogens are transmitted, or suspected to be transmitted, by Rhipicephalus sanguineus. Results of this study indicate that dogs from Grenada are infected with multiple tick-borne pathogens; therefore, tick-borne diseases should be included as differentials for dogs exhibiting thrombocytopenia, leukopenia, fever, or lethargy. One pathogen, E. canis, is also of potential public health significance.