Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia.

Mycobacterium tuberculosis (M.tb) is a globally distributed, obligate pathogen of humans that can be divided into seven clearly defined lineages. An emerging consensus places the origin and global dispersal of M.tb within the past 6,000 years: identifying how the ancestral clone of M.tb spread and differentiated within this timeframe is important for identifying the ecological drivers of the current pandemic. We used Bayesian phylogeographic inference to reconstruct the migratory history of M.tb in Africa and Eurasia and to investigate lineage specific patterns of spread from a geographically diverse sample of 552 M.tb genomes. Applying evolutionary rates inferred with ancient M.tb genome calibration, we estimated the timing of major events in the migratory history of the pathogen. Inferred timings contextualize M.tb dispersal within historical phenomena that altered patterns of connectivity throughout Africa and Eurasia: trans-Indian Ocean trade in spices and other goods, the Silk Road and its predecessors, the expansion of the Roman Empire, and the European Age of Exploration. We found that Eastern Africa and Southeast Asia have been critical in the dispersal of M.tb. Our results further reveal that M.tb populations have grown through range expansion, as well as in situ, and delineate the independent evolutionary trajectories of bacterial subpopulations underlying the current pandemic.

Identification of retinal breaks using subretinal trypan blue injection.

PURPOSE: To describe the use of subretinal trypan blue to identify retinal breaks during vitrectomy for rhegmatogenous retinal detachment (RD). DESIGN: Interventional case series. PARTICIPANTS: Five patients with RD in whom no retinal break could be identified by internal search with scleral indentation. METHODS: Trypan blue 0.15% was injected transretinally into the subretinal space using a 41-gauge cannula designed for macular translocation surgery. Perfluorocarbon heavy liquid was then injected into the vitreous cavity and the eye was rotated such that trypan blue was vented out of the break. The plume of trypan blue was used to identify retinal breaks, or in some cases staining of the break facilitated break detection. Subretinal fluid was then drained through the break or a drainage retinotomy and surgery was completed using standard techniques. MAIN OUTCOME MEASURE: Identification of previously unseen retinal breaks. RESULTS: This technique successfully identified a retinal break in 4 out of 5 patients. After absorption of the gas tamponade all retinas remained attached with a median visual acuity of 6/12. CONCLUSION: Failure to identify a retinal break during RD surgery is a well-recognized clinical challenge that may adversely affect outcome. In this setting, chromophore-assisted retinal break detection may be a useful surgical technique.

A molecular portrait of maternal sepsis from Byzantine Troy.

Pregnancy complications are poorly represented in the archeological record, despite their importance in contemporary and ancient societies. While excavating a Byzantine cemetery in Troy, we discovered calcified abscesses among a woman's remains. Scanning electron microscopy of the tissue revealed 'ghost cells', resulting from dystrophic calcification, which preserved ancient maternal, fetal and bacterial DNA of a severe infection, likely chorioamnionitis. Gardnerella vaginalis and Staphylococcus saprophyticus dominated the abscesses. Phylogenomic analyses of ancient, historical, and contemporary data showed that G. vaginalis Troy fell within contemporary genetic diversity, whereas S. saprophyticus Troy belongs to a lineage that does not appear to be commonly associated with human disease today. We speculate that the ecology of S. saprophyticus infection may have differed in the ancient world as a result of close contacts between humans and domesticated animals. These results highlight the complex and dynamic interactions with our microbial milieu that underlie severe maternal infections.

Genomic Evidence Establishes Anatolia as the Source of the European Neolithic Gene Pool.

Anatolia and the Near East have long been recognized as the epicenter of the Neolithic expansion through archaeological evidence. Recent archaeogenetic studies on Neolithic European human remains have shown that the Neolithic expansion in Europe was driven westward and northward by migration from a supposed Near Eastern origin [1-5]. However, this expansion and the establishment of numerous culture complexes in the Aegean and Balkans did not occur until 8,500 before present (BP), over 2,000 years after the initial settlements in the Neolithic core area [6-9]. We present ancient genome-wide sequence data from 6,700-year-old human remains excavated from a Neolithic context in Kumtepe, located in northwestern Anatolia near the well-known (and younger) site Troy [10]. Kumtepe is one of the settlements that emerged around 7,000 BP, after the initial expansion wave brought Neolithic practices to Europe. We show that this individual displays genetic similarities to the early European Neolithic gene pool and modern-day Sardinians, as well as a genetic affinity to modern-day populations from the Near East and the Caucasus. Furthermore, modern-day Anatolians carry signatures of several admixture events from different populations that have diluted this early Neolithic farmer component, explaining why modern-day Sardinian populations, instead of modern-day Anatolian populations, are genetically more similar to the people that drove the Neolithic expansion into Europe. Anatolia's central geographic location appears to have served as a connecting point, allowing a complex contact network with other areas of the Near East and Europe throughout, and after, the Neolithic.

The Role of Chorioretinal Biopsy in the Diagnosis of Intraocular Lymphoma.

PURPOSE: To assess the clinical usefulness of chorioretinal biopsy in establishing a definitive diagnosis in intraocular lymphomas. DESIGN: Retrospective, noncomparative, consecutive diagnostic case series. METHODS: setting: Moorfields Eye Hospital, London, United Kingdom. PATIENTS: Twenty-nine consecutive patients presenting with severe uveitis that required an intraocular biopsy where underlying lymphoma was suspected. OBSERVATION PROCEDURE: A retrospective review of a 15-year period (1999-2014) was undertaken of all patients that have undergone chorioretinal biopsy for suspected lymphoma at Moorfields Eye Hospital, London, United Kingdom. Patients were identified on the hospital's computerized database. MAIN OUTCOME MEASURES: Effectiveness of chorioretinal biopsy in establishing a definitive diagnosis or in excluding malignancy. RESULTS: A specific histologic diagnosis was made in 17 cases (59%) while in 9 cases the biopsy combined with clinical data was effective in excluding malignancy. In the 3 remaining cases, no specific diagnosis was made. No intraoperative complications were reported. Postoperative complications other than cataract included 2 vitreous hemorrhages and 2 retinal detachments. Of the 17 cases with a histologic diagnosis, 15 were obtained in eyes with marked vitritis, as opposed to 2 with minimal vitritis. CONCLUSIONS: Chorioretinal biopsy provided a definitive diagnosis of lymphoma in 59% of cases and assisted in exclusion of a further 31% in this series. The level of vitritis appears to act as a strong index of likelihood in achieving a definitive histologic diagnosis.

Guidance for the treatment of neovascular age-related macular degeneration.

Neovascular age-related macular degeneration is becoming an increasing socio-medical problem as the proportion of the aged population is continuously increasing. However, new insights in the pathogenesis of the disease offer the opportunity to develop targeted therapies that attack the disease process more successfully than ever. This review article will focus on summarizing the actual options in the management of neovascular age-related macular degeneration and provide a short overview about recent therapeutic options in clinical and preclinical evaluation. The recent development of anti-VEGF substances for use in clinical routine has markedly improved the prognosis of patients with neovascular AMD. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF), for the first time in the history of AMD treatments, results in a significant increase in visual acuity in patients with neovascular AMD. Overall, antiangiogenic approaches provide vision maintenance in over 90% and substantial improvement in 25-40% of patients. The combination with occlusive therapies like photodynamic therapy (PDT) potentially offers a reduction of re-treatment frequency and long-term maintenance of the treatment benefit. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. Nevertheless, the growing number of novel therapeutic options will have to provide proof of concept in randomized controlled clinical trials, a major challenge in view of the rapidly evolving field. For those therapies, which are already in clinical use, reasonable diagnostic tools for follow-up need to be developed, as the burden of continuous clinical monitoring of all patients and all indications is significant for patients and doctors. Ultimately, economic issues will be the limiting factor for the clinical availability of different treatment options.