Outcome of Pediatric Cataract Surgeries in a Tertiary Center in Switzerland

Purpose. To determine and to analyze the outcome of pediatric cataract surgery. Methods. A retrospective chart review of individuals aged up to 10 years who underwent cataract surgery between January 1, 2004, and December 31, 2014, at the UniversityHospital Zurich, Switzerland. Results. 63 children (94 affected eyes) with bilateral (68/94) or unilateral (26/94) cataract were identified. Surgery was performed at a median age of 1.5 months (IQR: 1.3–2.6 months) for the aphakic group (45/94) and of 50.7 months (IQR: 38.0–78.4 months) for the IOL group (49/94). At the last follow-up visit (median 31.1 months, IQR: 18.4–50.2 months), visual acuity was better in bilateral than in unilateral cataract cases. Posterior capsular opacification (PCO) was diagnosed in 30.9% of eyes without a significant difference in the IOL and aphakic groups (p=0.12). Aphakic glaucoma was diagnosed in 12/45 eyes at a median of 6.8 months (IQR 2.1–13.3 months) after surgery. Microcornea (5/12) and anterior segment anomalies (8/12) were associated with glaucoma development (p<0.05). Conclusion. Laterality and timing of surgery influence the outcome of pediatric cataract surgery. PCO was the most frequent postoperative complication. Aphakic glaucoma is often associated with ocular developmental abnormalities and a poor visual outcome

Functional and Morphological Characteristics of the Retina of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus Treated with Hydroxychloroquine: A Retrospective Study

Purpose: To evaluate the impact of drusen-like deposits (DLD) on retinal layer integrity and retinal function by optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in patients with systemic lupus erythematosus (SLE). Methods: We identified 66 eyes of 33 SLE patients treated with hydroxychloroquine (HCQ) that were categorized into two groups according to whether DLDs were present (34 eyes, Group One) or absent (32 eyes, Group Two). The groups were matched for age, sex, HCQ treatment duration, daily, and cumulative dosage. OCT (retinal layer thicknesses, central retinal thickness, CRT) and mfERG concentric ring analysis were analyzed and compared. Results: CRT was significantly thicker in Group One compared to Group Two (273.21 ± 3.96 vs. 254.5 ± 7.62) (p = 0.023). Group One also demonstrated an overall thicker retinal pigment epithelium compared to Group Two; however, the other outer retinal layers, outer nuclear layer, and photoreceptor layer were found to be significantly thinner in Group One compared to Group Two. We found no differences in mfERG parameters between the two groups. Conclusions: DLDs in SLE patients lead to abnormal central retinal layer thickness, which has no measurable impact on cone-mediated retinal function assessed by mfERG

Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Constraints from orbital motions around the Earth of the environmental fifth-force hypothesis for the OPERA superluminal neutrino phenomenology

It has been recently suggested by Dvali and Vikman that the superluminal neutrino phenomenology of the OPERA experiment may be due to an environmental feature of the Earth, naturally yielding a long-range fifth force of gravitational origin whose coupling with the neutrino is set by the scale M_*, in units of reduced Planck mass. Its characteristic length lambda should not be smaller than one Earth's radius R_e, while its upper bound is expected to be slightly smaller than the Earth-Moon distance (60 R_e). We analytically work out some orbital effects of a Yukawa-type fifth force for a test particle moving in the modified field of a central body. Our results are quite general since they are not restricted to any particular size of lambda; moreover, they are valid for an arbitrary orbital configuration of the particle, i.e. for any value of its eccentricity $e$. We find that the dimensionless strength coupling parameter alpha is constrained to |alpha| <= 1 10^-10-4 10^-9 for 1 R_e <= lambda <= 10 R_e by the laser data of the Earth's artificial satellite LAGEOS II, corresponding to M_* >= 4 10^9 -1.6 10^10. The Moon perigee allows to obtain |alpha| <= 3 10^-11 for the Earth-Moon pair in the range 15 R_e <= lambda = 3 10^10 - 4.5 10^10. Our results are neither necessarily limited to the superluminal OPERA scenario nor to the Dvali-Vikman model, in which it is M_* = 10^-6 at lambda = 1 R_e, in contrast with our bounds: they generally extend to any theoretical scenario implying a fifth-force of Yukawa-type.Comment: LaTex2e, 18 pages, 4 figures, 1 table, 81 reference

Advances in intravesical drug delivery systems to treat bladder cancer

Chemotherapeutic agents administered intravesically to treat bladder cancer have limited efficacy due to periodic dilution and wash-out during urine formation and elimination. This review describes the pathophysiology, prevalence and staging of bladder cancer, and discusses several formulation strategies used to improve drug residence within the bladder. These include the use of amphiphilic copolymers, mucoadhesive formulations, hydrogels, floating systems, and liposomes. Various in vitro and in vivo models recently employed for intravesical drug delivery studies are discussed. Some of the challenges that have prevented the clinical use of some promising formulations are identified

Active afforestation of drained peatlands is not a viable option under the EU Nature Restoration Law

The EU Nature Restoration Law (NRL) is critical in restoring degraded ecosystems. However, active afforestation of degraded peatlands has been suggested by some as a restoration measure under the NRL. Here, we discuss the current state of scientific evidence on the climate mitigation effects of peatlands under forestry and its limitations, uncertainties and evidence gaps. Based on this discussion we conclude: Afforestation of drained peatlands, while maintaining their drained state, is not equivalent to ecosystem restoration. This approach will not restore the peatland ecosystem's flora, fauna, and functions. There is insufficient evidence to support the long-term climate change mitigation benefits of active afforestation of drained peatlands. Most studies only focus on the short-term gains in standing biomass and rarely explore the full life cycle emissions associated with afforestation of drained peatlands. Thus, it is unclear whether the CO2 sequestration of a forest on drained peatland can offset the carbon loss from the peat over the long term. In some ecosystems, such as abandoned or certain cutaway peatlands, afforestation may provide short-term benefits for climate change mitigation compared to taking no action. However, this approach violates the concept of sustainability by sacrificing the most space-effective carbon store of the terrestrial biosphere, the long-term peat store, for a shorter-term, less space-effective, and more vulnerable carbon store, namely tree biomass. Consequently, active afforestation of drained peatlands is not a viable option for climate mitigation under the EU Nature Restoration Law and might even impede future rewetting/restoration efforts. To restore degraded peatlands, hydrological conditions must first be improved, primarily through rewetting

Convenient method for resolving degeneracies due to symmetry of the magnetic susceptibility tensor and its application to pseudo contact shift-based protein–protein complex structure determination

Pseudo contact shifts (PCSs) induced by paramagnetic lanthanide ions fixed in a protein frame provide long-range distance and angular information, and are valuable for the structure determination of protein–protein and protein–ligand complexes. We have been developing a lanthanide-binding peptide tag (hereafter LBT) anchored at two points via a peptide bond and a disulfide bond to the target proteins. However, the magnetic susceptibility tensor displays symmetry, which can cause multiple degenerated solutions in a structure calculation based solely on PCSs. Here we show a convenient method for resolving this degeneracy by changing the spacer length between the LBT and target protein. We applied this approach to PCS-based rigid body docking between the FKBP12-rapamycin complex and the mTOR FRB domain, and demonstrated that degeneracy could be resolved using the PCS restraints obtained from two-point anchored LBT with two different spacer lengths. The present strategy will markedly increase the usefulness of two-point anchored LBT for protein complex structure determination

EnzyMiner: automatic identification of protein level mutations and their impact on target enzymes from PubMed abstracts

BACKGROUND: A better understanding of the mechanisms of an enzyme's functionality and stability, as well as knowledge and impact of mutations is crucial for researchers working with enzymes. Though, several of the enzymes' databases are currently available, scientific literature still remains at large for up-to-date source of learning the effects of a mutation on an enzyme. However, going through vast amounts of scientific documents to extract the information on desired mutation has always been a time consuming process. In this paper, therefore, we describe an unique method, termed as EnzyMiner, which automatically identifies the PubMed abstracts that contain information on the impact of a protein level mutation on the stability and/or the activity of a given enzyme. RESULTS: We present an automated system which identifies the abstracts that contain an amino-acid-level mutation and then classifies them according to the mutation's effect on the enzyme. In the case of mutation identification, MuGeX, an automated mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure. For impact analysis, document classification is performed to identify the abstracts that contain a change in enzyme's stability or activity resulting from the mutation. The system was trained on lipases and tested on amylases with an accuracy of 85%. CONCLUSION: EnzyMiner identifies the abstracts that contain a protein mutation for a given enzyme and checks whether the abstract is related to a disease with the help of information extraction and machine learning techniques. For disease related abstracts, the mutation list and direct links to the abstracts are retrieved from the system and displayed on the Web. For those abstracts that are related to non-diseases, in addition to having the mutation list, the abstracts are also categorized into two groups. These two groups determine whether the mutation has an effect on the enzyme's stability or functionality followed by displaying these on the web

Shotgun sequencing of Yersinia enterocolitica strain W22703 (biotype 2, serotype O:9): genomic evidence for oscillation between invertebrates and mammals

<p>Abstract</p> <p>Background</p> <p><it>Yersinia enterocolitica </it>strains responsible for mild gastroenteritis in humans are very diverse with respect to their metabolic and virulence properties. Strain W22703 (biotype 2, serotype O:9) was recently identified to possess nematocidal and insecticidal activity. To better understand the relationship between pathogenicity towards insects and humans, we compared the W22703 genome with that of the highly pathogenic strain 8081 (biotype1B; serotype O:8), the only <it>Y. enterocolitica </it>strain sequenced so far.</p> <p>Results</p> <p>We used whole-genome shotgun data to assemble, annotate and analyse the sequence of strain W22703. Numerous factors assumed to contribute to enteric survival and pathogenesis, among them osmoregulated periplasmic glucan, hydrogenases, cobalamin-dependent pathways, iron uptake systems and the <it>Yersinia </it>genome island 1 (YGI-1) involved in tight adherence were identified to be common to the 8081 and W22703 genomes. However, sets of ~550 genes revealed to be specific for each of them in comparison to the other strain. The plasticity zone (PZ) of 142 kb in the W22703 genome carries an ancient flagellar cluster Flg-2 of ~40 kb, but it lacks the pathogenicity island YAPI_Ye, the secretion system <it>ysa </it>and <it>yts1</it>, and other virulence determinants of the 8081 PZ. Its composition underlines the prominent variability of this genome region and demonstrates its contribution to the higher pathogenicity of biotype 1B strains with respect to W22703. A novel type three secretion system of mosaic structure was found in the genome of W22703 that is absent in the sequenced strains of the human pathogenic <it>Yersinia </it>species, but conserved in the genomes of the apathogenic species. We identified several regions of differences in W22703 that mainly code for transporters, regulators, metabolic pathways, and defence factors.</p> <p>Conclusion</p> <p>The W22703 sequence analysis revealed a genome composition distinct from other pathogenic <it>Yersinia enterocolitica </it>strains, thus contributing novel data to the <it>Y. enterocolitica </it>pan-genome. This study also sheds further light on the strategies of this pathogen to cope with its environments.</p