A novel and practical technique to facilitate lead insertion at the His bundle region.

BACKGROUND: His bundle (HB) pacing techniques are challenging and time-consuming. This is primarily due to the limitations in locating the relatively small area of the HB body for pacing. METHODS: Permanent HB pacing was performed in 133 consecutive patients with symptomatic bradycardia. A right atrial septo-gram (RAS) was performed in all patients to locate the HB. Briefly, 8-10 cc of contrast was injected through the Medtronic C315HIS delivery sheath while fluoroscopy cine runs were obtained in the RAO 15-20° projection. The images obtained provided the visualization of an approximately 90° angle composed by the medial aspect of the tricuspid valve annulus (TVA) anteriorly and the superior aspect of the interatrial septum superiorly. The apex of this angle coincides with the tip of the triangle of Koch (TK), where the HB body is usually located. A Medtronic SelectSecure™ MRI SureScan™ Model 3830 lead was then advanced and directed towards this area. The HB was mapped using pace mapping and unipolar recordings from the lead tip. RESULTS: Localization of the apex of the TK/HB body with the RAS was successful in all patients. The overall acute success of inserting the lead at the HB was 95%. CONCLUSION: This study demonstrated that our method of utilizing a RAS to facilitate the localization the HB body proved to be safe and efficient in achieving permanent HB pacing with a success rate higher than previously reported.

Exogenous leptin promotes reproductive behavior during aphagia in red-sided garter snakes (Thamnophis sirtalis parietalis).

Despite the established dichotomy between investment in either reproduction or self-maintenance, a hormonal mechanism that influences an organism's decision to prioritize these behaviors remains elusive. The protein hormone leptin is a likely candidate because it is secreted from adipocytes in proportion to the amount of stored fat in numerous species. Although the majority of studies suggest that leptin stimulates reproduction, the actions of leptin can be context-dependent. Leptin increases sexual behavior in fed individuals, but inhibits sexual behavior in food-restricted individuals. We investigated if exogenous leptin influences sexual behavior in red-sided garter snakes (Thamnophis sirtalis parietalis) experiencing a predictable bout of aphagia during the mating season. We tested two doses of recombinant murine leptin injected for three days. Males were subjected to three mating trials, one on each day of injections, while females were subjected to one mating trial on the last day of injections. Leptin affects male and female snakes similarly by increasing both appetitive (i.e., mating behavior score) and consummatory (i.e., number of copulations, proportion of individuals copulated) sex behavior. We found no evidence to suggest that leptin influenced latency to copulate or duration of copulation. Because leptin promotes reproductive behavior in non-feeding garter snakes, these findings do not align with research on food-restricted mammals. Further investigations into how leptin affects sexual behavior in snakes exposed to food-restriction manipulations would clarify if the role of leptin is evolutionarily divergent.

Physiological correlates of reproductive decisions: Relationships among body condition, reproductive status, and the hypothalamus-pituitary-adrenal axis in a reptile.

When opportunities to feed and reproduce are limited, females are often unable to recover sufficient energy stores to reproduce in consecutive years. Body condition has been used as a proxy for recent reproductive history in such species. We previously found that glucocorticoid responses to capture stress vary with body condition in female red-sided garter snakes (Thamnophis sirtalis parietalis), a species with limited seasonal breeding opportunities. Because variation in glucocorticoid receptor (GR) protein in the brain could explain these differences, we first assessed GR protein content in females in different body conditions. To investigate if body condition during the spring mating season accurately reflects recent reproductive history, we measured glucocorticoid responses to stress in females with different body conditions, assessed their mating behavior and brought mated females to our lab to determine which females would give birth during the summer (i.e., were parturient). Female red-sided garter snakes reproduce biennially, and therefore mated females that did not give birth were deemed non-parturient. In this study, glucocorticoid stress responses and mating behavior did not vary with body condition, nor was body condition related to brain GR or reproductive condition (parturient vs non-parturient). Only unreceptive females showed a significant stress-induced increase in glucocorticoids, suggesting that reduced stress responsiveness is associated with receptivity. Parturient females mated faster (were more proceptive) than non-parturient females. These data suggest that HPA axis activity modulates receptivity, while proceptivity is related primarily to reproductive condition.

Frequency and Type of Conflicts of Interest in the Peer Review of Basic Biomedical Research Funding Applications: Self-Reporting Versus Manual Detection.

Despite the presumed frequency of conflicts of interest in scientific peer review, there is a paucity of data in the literature reporting on the frequency and type of conflicts that occur, particularly with regard to the peer review of basic science applications. To address this gap, the American Institute of Biological Sciences (AIBS) conducted a retrospective analysis of conflict of interest data from the peer review of 282 biomedical research applications via several onsite review panels. The overall conflicted-ness of these panels was significantly lower than that reported for regulatory review. In addition, the majority of identified conflicts were institutional or collaborative in nature. No direct financial conflicts were identified, although this is likely due to the relatively basic science nature of the research. It was also found that 65 % of identified conflicts were manually detected by AIBS staff searching reviewer CVs and application documents, with the remaining 35 % resulting from self-reporting. The lack of self-reporting may be in part attributed to a lack of perceived risk of the conflict. This result indicates that many potential conflicts go unreported in peer review, underscoring the importance of improving detection methods and standardizing the reporting of reviewer and applicant conflict of interest information.

Pheromonal mediation of intraseasonal declines in the attractivity of female red-sided garter snakes, Thamnophis sirtalis parietalis.

During the breeding season, female red-sided garter snakes (Thamnophis sirtalis parietalis) produce and express a sexual attractiveness pheromone that elicits male courtship behavior. Composed of a homologous series of saturated and monounsaturated methyl ketones, this pheromone is expressed in female skin lipids. Recent studies have shown that the sexual attractivity of unmated female garter snakes declines as the breeding season progresses. Here, we investigated whether temporal changes in the quantity and/or quality of the female sexual attractiveness pheromone are responsible for the observed loss of attractivity. Female red-sided garter snakes were collected immediately following spring emergence and held under natural conditions for the duration of the breeding season. Behavioral experiments confirmed that unmated females become significantly less attractive to males within two weeks of emergence from hibernation. Additionally, these females had lower estradiol concentrations at two weeks post-emergence. Subsequent chemical analyses revealed qualitative variation between the pheromone profiles of newly emerged females and those of females at two weeks post-emergence. Together, these results support the hypothesis that changes in the female sexual attractiveness pheromone are responsible for declining post-emergence female attractivity in garter snakes.

Effects of melatonin on the behavioral and hormonal responses of red-sided garter snakes (Thamnophis sirtalis parietalis) to exogenous corticosterone.

We investigated possible interactions between melatonin and corticosterone in modulating the reproductive behavior of male red-sided garter snakes (Thamnophis sirtalis parietalis) following spring emergence. We also examined whether melatonin's modulatory actions could be explained by its potential properties as a serotonin receptor antagonist. Exogenous corticosterone significantly reduced courtship behavior of male snakes in a dose-dependent manner. Melatonin also significantly reduced courtship behavior of male garter snakes. Pretreatment with melatonin before administering corticosterone treatments further suppressed courtship behavior of red-sided garter snakes. These results indicate additive inhibitory effects of melatonin and corticosterone in modulating reproductive behavior. Snakes receiving ketanserin, a serotonergic type 2A receptor antagonist, followed by corticosterone also showed reduced courtship behavior; this serotonin receptor antagonist followed by treatment with vehicle did not significantly influence courtship behavior of male snakes. Neither melatonin nor corticosterone treatments significantly influenced testosterone + 5-alpha-dihydrotestosterone concentrations of male garter snakes, supporting a direct effect of melatonin and corticosterone on courtship behavior that is independent of any effect on androgen concentrations. We propose that a serotonin system is involved in the modulation of male courtship behavior by melatonin and corticosterone. In addition, our data support the hypothesis that melatonin may function as a serotonin receptor antagonist. Further research is necessary to discern whether the actions of melatonin and corticosterone are converging on the same pathway or if their effects on different pathways are having additive inhibitory effects on courtship behavior.

Pheromonally mediated sexual isolation among denning populations of red-sided garter snakes, Thamnophis sirtalis parietalis.

Utilizing behavioral experiments and chemical analyses, we examined whether pheromonally mediated sexual isolation exists between denning populations of red-sided garter snakes (Thamtnophis sirtalis parietalis) in Manitoba, Canada. Simultaneous choice tests conducted during the breeding season revealed that adult males from a hibernaculum in central Manitoba displayed a strong courtship preference for females from their own population over females from a hibernaculum in western Manitoba, whereas males from the western Manitoba hibernaculum showed no such preference. In addition. trailing experiments testing the response of males from the two hibernacula to familiar and unfamiliar female trails showed similar results, demonstrating that the observed male preference is mediated through chemical cues. Subsequent chemical analysis of the female sexual attractiveness pheromone. a homologous series of long-chain saturated and (omega-9 cis-unsaturated methyl ketones responsible for eliciting male courtship behavior and trailing behavior in garter snakes, showed significant variation in the composition of the pheromone between the two populations. Specifically, the two populations varied in the relative concentrations of individual unsaturated methyl ketones expressed by females. These results suggest that sexual isolation exists to a degree among denning populations of red-sided garter snakes due to variation in the expression of the female sexual attractiveness pheromone.

Reproductive isolating mechanisms between two sympatric sibling species of sea snakes.

Mechanisms that maintain species isolation within sympatric congeners have attracted analysis in many kinds of organisms, but not in snakes. We studied two sibling species of amphibious sea snakes (Laticauda colubrina and L. frontalis) on the island of Efate, in the Pacific Ocean republic of Vanuatu. The two taxa are almost identical morphologically, except that L. colubrina grows much larger than L. frontalis. No natural hybrids have been reported, and geographic distributions of the two taxa suggest the possibility of sympatric speciation. Our fieldwork shows that the two taxa are often syntopic and overlap in breeding seasons. Behavioral studies in outdoor arenas show that the separation between these two taxa is maintained by species-specific cues that control male courtship. Males of both species courted conspecific females but not heterospecific females. The proximate mechanism driving this separation involves chemical cues. Adult females of both taxa possess distinctive lipids in the skin. Males directed courtship behavior (chin-pressing) to hexane-extracted samples of lipids from conspecific but not heterospecific females. Males of the dwarf species (L frontalis) were more selective courters than were those of the larger taxon (L. colubrina), perhaps because a preference for courting larger females means that L. colubrina males would be unlikely to court L. frontalis-sized (i.e., small) females even in the absence of pheromonal barriers.

Variation in a female sexual attractiveness pheromone controls male mate choice in garter snakes.

Male red-sided garter snakes (Thamnophis sirtalis parietalis) display a courtship preference for larger females during the breeding season. Utilizing behavioral experiments and chemical analyses, we tested the hypothesis that males can discriminate among females of varying size solely by means of the sexual attractiveness pheromone, a previously characterized sex pheromone composed of a homologous series of long-chain saturated and omega-9 cis-unsaturated methyl ketones contained in the skin lipids of females. When presented with skin lipid extracts from large and small females, a greater proportion of males displayed courtship behaviors to large female extracts. This demonstrates that there is an intrinsic property of the female skin lipids that allows males to differentiate among large and small females. Analysis of the sexual attractiveness pheromone revealed that the necessary variation exists for this pheromone to function as a reliable indicator to males of female body size. Specifically, we observed a strong correlation between female snout-vent length and the relative concentration of saturated and omega-9 cis-unsaturated methyl ketones composing the pheromone; smaller females expressed pheromone profiles higher in saturated methyl ketones. while larger females expressed pheromone profiles dominated by unsaturated methyl ketones. The results of this study suggest that male red-sided garter snakes utilize compositional variation in the female sexual attractiveness pheromone to differentiate among potential mates of varying size.