Long-term outcomes after acute primary angle closure in a White Caucasian population

IntroductionVery limited data is available on the morbidity and progression to primary angle closure glaucoma (PACG) in White Caucasian individuals following acute primary angle closure (APAC).Our aim is to identify the number of eyes who developed PACG following an APAC attack and to determine the risk factors for PACG development in a White Caucasian population in the United Kingdom (UK). We assessed the rate of blindness and visual impairment in the affected eye as defined by the World Health Organisation.MethodsRetrospective observational study including 48 consecutive eyes of 46 White Caucasian subjects who presented with APAC to a tertiary referral unit in the United Kingdom.Eyes affected by glaucomatous optic neuropathy at presentation were excluded. We included in our analysis socio-demographic variables, ophthalmic findings, investigations and treatment.ResultsThe mean final follow up period was 27 months ± 14 standard deviation (SD). Seven (15 %) eyes developed PACG. Statistical analysis showed that the following factors were linked to a higher risk of progression: length of symptoms before presentation and time taken to break the attack. The intraocular pressure (IOP) was significantly higher in the group who developed PACG at the one- and six-month visit compared to the group which did not develop the disease.At the final visit 3 (6 %) eyes were blind while 5 (10 %) were visually impaired. PACG was responsible for visual impairment in 2 (4 %) eyes but not for any case of blindness.ConclusionsDelayed presentation, length of time taken to break the attack and poor IOP control can result in PACG development and visual impairment. APAC causes a low long-term visual morbidity in White Caucasians

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

The genome of the Gulf pipefish enables understanding of evolutionary innovations

BACKGROUND: Evolutionary origins of derived morphologies ultimately stem from changes in protein structure, gene regulation, and gene content. A well-assembled, annotated reference genome is a central resource for pursuing these molecular phenomena underlying phenotypic evolution. We explored the genome of the Gulf pipefish (Syngnathus scovelli), which belongs to family Syngnathidae (pipefishes, seahorses, and seadragons). These fishes have dramatically derived bodies and a remarkable novelty among vertebrates, the male brood pouch. RESULTS: We produce a reference genome, condensed into chromosomes, for the Gulf pipefish. Gene losses and other changes have occurred in pipefish hox and dlx clusters and in the tbx and pitx gene families, candidate mechanisms for the evolution of syngnathid traits, including an elongated axis and the loss of ribs, pelvic fins, and teeth. We measure gene expression changes in pregnant versus non-pregnant brood pouch tissue and characterize the genomic organization of duplicated metalloprotease genes (patristacins) recruited into the function of this novel structure. Phylogenetic inference using ultraconserved sequences provides an alternative hypothesis for the relationship between orders Syngnathiformes and Scombriformes. Comparisons of chromosome structure among percomorphs show that chromosome number in a pipefish ancestor became reduced via chromosomal fusions. CONCLUSIONS: The collected findings from this first syngnathid reference genome open a window into the genomic underpinnings of highly derived morphologies, demonstrating that de novo production of high quality and useful reference genomes is within reach of even small research groups. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1126-6) contains supplementary material, which is available to authorized users