Discovery of novel alphacoronaviruses in European rodents and shrews

Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses

A novel gene controls a new structure: piggyBac transposable element-derived 1, unique to mammals, controls mammal-specific neuronal paraspeckles

Although new genes can arrive from modes other than duplication, few examples are well characterized. Given high expression in some human brain subregions and a putative link to psychological disorders [e.g., schizophrenia (SCZ)], suggestive of brain functionality, here we characterize piggyBac transposable element-derived 1 (PGBD1). PGBD1 is nonmonotreme mammal-specific and under purifying selection, consistent with functionality. The gene body of human PGBD1 retains much of the original DNA transposon but has additionally captured SCAN and KRAB domains. Despite gene body retention, PGBD1 has lost transposition abilities, thus transposase functionality is absent. PGBD1 no longer recognizes piggyBac transposon-like inverted repeats, nonetheless PGBD1 has DNA binding activity. Genome scale analysis identifies enrichment of binding sites in and around genes involved in neuronal development, with association with both histone activating and repressing marks. We focus on one of the repressed genes, the long noncoding RNA NEAT1, also dysregulated in SCZ, the core structural RNA of paraspeckles. DNA binding assays confirm specific binding of PGBD1 both in the NEAT1 promoter and in the gene body. Depletion of PGBD1 in neuronal progenitor cells (NPCs) results in increased NEAT1/paraspeckles and differentiation. We conclude that PGBD1 has evolved core regulatory functionality for the maintenance of NPCs. As paraspeckles are a mammal-specific structure, the results presented here show a rare example of the evolution of a novel gene coupled to the evolution of a contemporaneous new structure

4 Letters from concerned citizens in response to Brunswick Naval Air Station

Letters from citizens of Maine to the BRAC Commission in response to the possible realignment of Brunswick Naval Air Station

Long-term efficacy of combined phacoemulsification plus trabeculectomy versus phacoemulsification plus excimer laser trabeculotomy

Background Combined cataract and glaucoma procedures, and minimally-invasive glaucoma surgery in particular, have gained increasing interest over the past few years. The aim of this study was to compare the long-term efficacy of combined phaco-trabeculectomy (Phaco-Trab) and combined phacoemulsification plus excimer laser trabeculotomy (Phaco-ELT). Patients and Methods Retrospective, non-randomised, comparative, interventional case series of consecutive patients after Phaco-Trab and Phaco-ELT at the University Hospital of Zurich and the Talacker Eye Center Zurich in Switzerland. Inclusion criteria were diagnosis of glaucoma plus vision-impairing coexisting cataract. Primary outcome measures were change in intraocular pressure (IOP), number of anti-glaucoma drugs (AGDs), and best-corrected visual acuity (BCVA) 1 year and 4 years after the procedure. Secondary outcome measures were surgical complications and requirement of postoperative interventions. Success was defined based on the criteria of the Tube-versus-Trabeculectomy study. Results Mean age was 76.1 ± 8.6 years (29.2 % males; 47.8 % right eyes). Phaco-Trab (n = 62) decreased median IOP from 22.8 to 13.0 at 1 year and to 14.0 mmHg at 4 years. AGDs were reduced from 2 drugs to 0 AGDs at 1 year and 4 years. Median BCVA improved from 0.2 logMAR to 0.0 logMAR at 1 year and 4 years. Phaco-ELT (n = 51) lowered median IOP from 19.0 to 15.0 at 1 year and to 14.0 mmHg (p = 0.002) at 4 years. AGDs were reduced from 2 drugs to 1 AGD at 1 year and 4 years (p = 0.002). BCVA improved from 0.4 logMAR to 0.1 logMAR after 1 year and 4 years. If not stated otherwise, all changes compared to baseline were highly significant (p < 0.001). No perioperative complications occurred; postoperative interventions were performed in 74 % of Phaco-Trab patients. Conclusion Both surgical procedures reduced IOP and AGDs and improved BCVA significantly and persistently during the entire follow-up period of 4 years with a good safety profile. This study validates Phaco-ELT as an option when post-operative target pressure in the mid-teens would be adequate, whereas Phaco-Trab would be the treatment of choice when IOP in the low teens is desired

Evaluation von Korrekturformeln für die Tonometrie : Die Goldmann-Applanationstonometrie in Annäherung zur dynamischen Contour-Tonometrie

BACKGROUND Accurate determination of intraocular pressure (IOP) is essential for correct management of glaucoma. Goldmann applanation tonometry (GAT) is the gold standard for measuring IOP despite its limitations due to its dependence on corneal properties. With the aim of improving the accuracy of GAT readings, several correction formulas have been developed. OBJECTIVE The aim of this study was to investigate the accuracy and clinical relevance of five correction equations for GAT. MATERIAL AND METHODS Prospective study of 112 glaucoma patients at the University Hospital and Talacker Eye Center, Zurich, Switzerland. The IOP was measured with GAT and dynamic contour tonometry (DCT) in randomized order. The GAT readings were adjusted with five correction equations. The primary study endpoint was the degree of concordance between corrected GAT and DCT readings. A discordance of ≥2 mm Hg was defined as significant. The association between discordant IOP measurements and central corneal thickness (CCT) was the secondary study endpoint. RESULTS The mean patient age was 66 ± 13 years (60% females and 56% left eyes). The mean IOP was 17.0 mm Hg for GAT and 20.3 mm Hg for DCT, with a discordance of 3.3 mm Hg between GAT und DCT. The discordances between DCT and the corrected values ranged from 2.7 to 5.4 mm Hg. Spearman's rank testing showed a positive correlation between CCT and the discordances of all correction equations and a negative correlation between CCT and the discordance of DCT and GAT. CONCLUSION The use of GAT correction formulas involves the risk of creating significant error. The correction equations examined showed extensive scatter and resulted in mean IOP values that were lower than the IOP initially measured by GAT. Thus the use of any correction equation may delay diagnosis of glaucoma and should be avoided

Phaco-trabeculectomy equals trabeculectomy in lowering IOP-A 4 years follow-up study

Objective: The aim of this study was to compare the long-term efficacy and safety of combined phacotrabeculectomy (phaco-trab) and trabeculectomy (trab) alone. Methods: Retrospective, non-randomized, interventional case series of phaco-trab and trab. Inclusion criteria were diagnosis of glaucoma for both plus vision impairing coexisting cataracts for phaco-trab. Primary outcome measures were change in intraocular pressure (IOP) and number of anti-glaucoma drugs (AGD) at 1 y and 4 ys after surgery, and postoperative interventions (i.e. laser suture lysis, 5-Fluorouracil injection, needling). Secondary outcome measures were visual acuity and complications. Success was defined based on the criteria from the tubeversus- trabeculectomy study. Results: Mean age was 73.6 ± 8.7 years (28% males; 51% right eyes). Median preoperative IOP was reduced from 22.8 mmHg to postoperative 13.0 mmHg at 1 y and to 14.0 mmHg at 4 ys after phaco-trab (n=62), or in trab alone (n=72) from 21.8 mmHg to 12.0 mmHg at 1 y and 4 ys. AGD were reduced from 2.5 ± 0.8 to 0.1 ± 0.3 1 y and 0.2 ± 0.6 4 ys after phaco-trab, and from 2.6 ± 1.0 to 0.2 ± 0.5 AGD 1 y and 4 ys after trab alone. Both IOP and AGD reduction were statistically indifferent between the groups at all-time points. Mean number of postoperative interventions was 2.1 for phaco-trab and 1.8 for trab (p=0.64). 75% of phaco-trab and 74% of trab eyes fulfilled the criteria for complete success after 4 ys (p=0.844). Conclusion: Both procedures resulted in an equally successful and stable long-term reduction of IOP to the lower teens and AGD requirement, together with a good safety profile. The high number of postoperative interventions in both groups emphasizes the importance of a close follow-up. We therefore conclude that if a close and careful postoperative follow-up can be guaranteed, phaco-trabeculectomy should be the treatment of choice for patients with coexisting cataract and otherwise uncontrolled IOP

Long-term efficacy of combined phacoemulsification plus trabeculectomy versus phacoemulsification plus excimer laser trabeculotomy

Background Combined cataract and glaucoma procedures, and minimally-invasive glaucoma surgery in particular, have gained increasing interest over the past few years. The aim of this study was to compare the long-term efficacy of combined phaco-trabeculectomy (Phaco-Trab) and combined phacoemulsification plus excimer laser trabeculotomy (Phaco-ELT). Patients and Methods Retrospective, non-randomised, comparative, interventional case series of consecutive patients after Phaco-Trab and Phaco-ELT at the University Hospital of Zurich and the Talacker Eye Center Zurich in Switzerland. Inclusion criteria were diagnosis of glaucoma plus vision-impairing coexisting cataract. Primary outcome measures were change in intraocular pressure (IOP), number of anti-glaucoma drugs (AGDs), and best-corrected visual acuity (BCVA) 1 year and 4 years after the procedure. Secondary outcome measures were surgical complications and requirement of postoperative interventions. Success was defined based on the criteria of the Tube-versus-Trabeculectomy study. Results Mean age was 76.1 ± 8.6 years (29.2 % males; 47.8 % right eyes). Phaco-Trab (n = 62) decreased median IOP from 22.8 to 13.0 at 1 year and to 14.0 mmHg at 4 years. AGDs were reduced from 2 drugs to 0 AGDs at 1 year and 4 years. Median BCVA improved from 0.2 logMAR to 0.0 logMAR at 1 year and 4 years. Phaco-ELT (n = 51) lowered median IOP from 19.0 to 15.0 at 1 year and to 14.0 mmHg (p = 0.002) at 4 years. AGDs were reduced from 2 drugs to 1 AGD at 1 year and 4 years (p = 0.002). BCVA improved from 0.4 logMAR to 0.1 logMAR after 1 year and 4 years. If not stated otherwise, all changes compared to baseline were highly significant (p < 0.001). No perioperative complications occurred; postoperative interventions were performed in 74 % of Phaco-Trab patients. Conclusion Both surgical procedures reduced IOP and AGDs and improved BCVA significantly and persistently during the entire follow-up period of 4 years with a good safety profile. This study validates Phaco-ELT as an option when post-operative target pressure in the mid-teens would be adequate, whereas Phaco-Trab would be the treatment of choice when IOP in the low teens is desired

A New Glaucoma Severity Score Combining Structural and Functional Defects

Background In order to assess glaucoma severity and to compare the success of surgical and medical therapy and study outcomes, an objective and independent staging tool is necessary. A combination of information from both structural and functional testing is probably the best approach to stage glaucomatous damage. There has been no universally accepted standard for glaucoma staging. The aim of this study was to develop a Glaucoma Severity Score (GSS) for objective assessment of a patient's glaucoma severity, combining both functional and structural information. Materials and methods The Glaucoma Severity Score includes the following 3 criteria: superior and inferior Retinal Nerve Fibre Layer (RNFL) thickness, perimetric mean defect (MD), and agreement of anatomical and perimetric defects, as assessed by two glaucoma specialists. The specialists defined a staging tool for each of the 3 criteria in a consensus process, assigning specific characteristics to a scale value between 0 and 2 or 0 and 3, respectively. The GSS ranges between 0 and 10 points. In a prospective observational study, the data of 112 glaucoma patients were assessed independently by the two specialists according to this staging tool. Results The GSS was applied to 112 eyes and patients (59.8 % female) with a mean age of 66.3 ± 13.1 years. Mean GSS was 4.73 points. Cohen's kappa coefficient was determined to measure inter-rater agreement between glaucoma specialists for the third criterion. With κ = 0.83, the agreement was very good. Thus, all 3 criteria of the GSS may be regarded as objective. Conclusions The Glaucoma Severity Score is an objective tool, combining both structural and functional characteristics, and permitting comparison of different patients, populations and studies. The Glaucoma Severity Score has proven effective in the objective assessment of 112 glaucoma patients and is relatively user-friendly in clinical practice. A comparative study of the GSS with the results of the FORUM® Glaucoma Workplace (Carl Zeiss Meditec AG, Jena, Germany) will be the next step. If outcomes match, the Glaucoma Severity Score can be accepted as a promising tool to stage glaucoma and monitor changes objectively in patients when comparing glaucoma progression in study analyses