Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy

Demographic reconstruction from ancient DNA supports rapid extinction of the great auk

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation

Synchronous diversification of Sulawesi's iconic artiodactyls driven by recent geological events

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back to 40 Ma. Recent studies, however, suggest that much of Sulawesi’s fauna assembled over the last 15 Myr. Here, we test the hypothesis that more recent uplift of previously submerged portions of land on Sulawesi promoted diversification and that much of its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructionswithgenetic andmorphometric datasets derived from Sulawesi’s three largest mammals: the babirusa, anoa and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Ma to 2-3 Ma), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that emergence of land on Sulawesi (approx. 1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicate that the establishment of the highly endemic faunal assemblage on Sulawesiwas driven by geological events over the last few million years

Determination of solid state characteristics of spray-congealed ibuprofen solid lipid microparticles and their impact on sustaining drug release

10.1021/acs.molpharmaceut.5b00015Molecular Pharmaceutics1251592-160

Dating the origin of hepatitis B virus reveals higher substitution rate and adaptation on the branch leading to F/H genotypes

The evolution of hepatitis B virus (HBV), particularly its origins and evolutionary timescale, has been the subject of debate. Three major scenarios have been proposed, variously placing the origin of HBV in humans and great apes from some million years to only a few thousand years ago (ka). To compare these scenarios, we analyzed 105 full-length HBV genome sequences from all major genotypes sampled globally. We found a high correlation between the demographic histories of HBV and humans, as well as coincidence in the times of origin of specific subgenotypes with human migrations giving rise to their host indigenous populations. Together with phylogenetic evidence, this suggests that HBV has co-expanded with modern humans. Based on the co-expansion, we conducted a Bayesian dating analysis to estimate a precise evolutionary timescale for HBV. Five calibrations were used at the origins of F/H genotypes, D4, C3 and B6 from respective indigenous populations in the Pacific and Arctic and A5 from Haiti. The estimated time for the origin of HBV was 34.1ka (95% highest posterior density interval 27.6-41.3ka), coinciding with the dispersal of modern non-African humans. Our study, the first to use full-length HBV sequences, places a precise timescale on the HBV epidemic and also shows that the "branching paradox" of the more divergent genotypes F/H from Amerindians is due to an accelerated substitution rate, probably driven by positive selection. This may explain previously observed differences in the natural history of HBV between genotypes F1 and A2, B1, and D. © 2015 Elsevier Inc

Dating the origin and dispersal of hepatitis B virus infection in humans and primates

The origin of hepatitis B virus (HBV) infection in humans and other primates remains largely unresolved. Understanding the origin of HBV is crucial because it provides a framework for studying the burden, and subsequently the evolution, of HBV pathogenicity with respect to changes in human population size and life expectancy. To investigate this controversy we examined the relationship between HBV phylogeny and genetic diversity of modern humans, investigated the timescale of global HBV dispersal, and tested the hypothesis of HBV-human co-divergence. We find that the global distribution of HBV genotypes and subgenotypes are consistent with the major prehistoric modern human migrations. We calibrate the HBV molecular clock using the divergence times of different indigenous human populations based on archaeological and genetic evidence and show that HBV jumped into humans around 33,600 years ago; 95% higher posterior density (HPD): 22,000-47,100 years ago (estimated substitution rate: 2.2 × 10-6; 95% HPD: 1.5-3.0 × 10-6 substitutions/site/year). This coincides with the origin of modern non-African humans. Crucially, the most pronounced increase in the HBV pandemic correlates with the global population increase over the last 5,000 years. We also show that the non-human HBV clades in orangutans and gibbons resulted from cross-species transmission events from humans that occurred no earlier than 6,100 years ago. Conclusion: Our study provides, for the first time, an estimated timescale for the HBV epidemic that closely coincides with dates of human dispersals, supporting the hypothesis that HBV has been co-expanding and co-migrating with human populations for the last 40,000 years. © 2012 American Association for the Study of Liver Diseases

The global spread of hepatitis C virus 1a and 1b: A phylodynamic and phylogeographic analysis

Background: Hepatitis C virus (HCV) is estimated to affect 130-180 million people worldwide. Although its origin is unknown, patterns of viral diversity suggest that HCV genotype 1 probably originated from West Africa. Previous attempts to estimate the spatiotemporal parameters of the virus, both globally and regionally, have suggested that epidemic HCV transmission began in 1900 and grew steadily until the late 1980s. However, epidemiological data suggest that the expansion of HCV may have occurred after the Second World War. The aim of our study was to elucidate the timescale and route of the global spread of HCV. Methods and Findings: We show that the rarely sequenced HCV region (E2P7NS2) is more informative for molecular epidemiology studies than the more commonly used NS5B region. We applied phylodynamic methods to a substantial set of new E2P7NS2 and NS5B sequences, together with all available global HCV sequences with information in both of these genomic regions, in order to estimate the timescale and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b. We showed that transmission of subtypes 1a and 1b "exploded" between 1940 and 1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence interval 15-17). Phylogeographic analysis of all available NS5B sequences suggests that HCV subtypes 1a and 1b disseminated from the developed world to the developing countries. Conclusions: The evolutionary rate of HCV appears faster than previously suggested. The global spread of HCV coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but slowed prior to the wide implementation of anti-HCV screening. Differences in the transmission routes associated with subtypes 1a and 1b provide an explanation of the relatively earlier expansion of 1b. Our data show that the most plausible route of the HCV dispersal was from developed countries to the developing world. © 2009 Magiorkinis et al

Mitochondrial phylogenomics resolves the global spread of higher termites, ecosystem engineers of the tropics

The higher termites (Termitidae) are keystone species and ecosystem engineers. They have exceptional biomass and play important roles in decomposition of dead plant matter, in soil manipulation, and as the primary food for many animals, especially in the tropics. Higher termites are most diverse in rainforests, with estimated origins in the late Eocene (54 Ma), postdating the breakup of Pangaea and Gondwana when most continents became separated. Since termites are poor fliers, their origin and spread across the globe requires alternative explanation. Here, we show that higher termites originated 42-54Ma in Africa and subsequently underwent at least 24 dispersal events between the continents in two main periods. Using phylogenetic analyses of mitochondrial genomes from 415 species, including all higher termite taxonomic and feeding groups, we inferred 10 dispersal events to South America and Asia 35-23Ma, coinciding with the sharp decrease in global temperature, sea level, and rainforest cover in the Oligocene. After global temperatures increased, 23-5Ma, there was only one more dispersal to South America but 11 to Asia and Australia, and one dispersal back to Africa. Most of these dispersal events were transoceanic and might have occurred via floating logs. The spread of higher termites across oceans was helped by the novel ecological opportunities brought about by environmental and ecosystem change, and led termites to become one of the few insect groups with specialized mammal predators. This has parallels with modern invasive species that have been able to thrive in humanimpacted ecosystems.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Inferring epidemiological parameters from phylogenetic information for the HIV-1 epidemic among MSM

The HIV-1 epidemic in Europe is primarily sustained by a dynamic topology of sexual interactions among MSM who have individual immune systems and behavior. This epidemiological process shapes the phylogeny of the virus population. Both fields of epidemic modeling and phylogenetics have a long history, however it remains difficult to use phylogenetic data to infer epidemiological parameters such as the structure of the sexual network and the per-act infectiousness. This is because phylogenetic data is necessarily incomplete and ambiguous. Here we show that the cluster-size distribution indeed contains information about epidemiological parameters using detailed numberical experiments. We simulate the HIV epidemic among MSM many times using the Monte Carlo method with all parameter values and their ranges taken from literature. For each simulation and the corresponding set of parameter values we calculate the likelihood of reproducing an observed cluster-size distribution. The result is an estimated likelihood distribution of all parameters from the phylogenetic data, in particular the structure of the sexual network, the per-act infectiousness, and the risk behavior reduction upon diagnosis. These likelihood distributions encode the knowledge provided by the observed cluster-size distrbution, which we quantify using information theory. Our work suggests that the growing body of genetic data of patients can be exploited to understand the underlying epidemiological process