Developmental or degenerative – NR2E3 gene mutations in two patients with enhanced S cone syndrome

PurposeEnhanced S Cone Syndrome is a rare autosomal recessive disorder characterized clinically by an absence of rod function, a replacement of most L and M cone function by S cone activity (Goldmann-Favre Syndrome) and by variable degrees of retinal degeneration in different families. The causative gene, nuclear receptor subfamily 2, group E, member 3 (NR2E3), controls the developmental sequence for rods and cones. The purpose of this study was to compare the nature and implications of mutations in two subjects with Enhanced S Cone Syndrome who have significantly different degrees of degenerative damage.MethodsA direct sequencing approach was used to identify the mutations. Genomic DNA was amplified from all the exons of NR2E3 and used as a template for sequencing. Of the two families studied, Case 1 is of Persian ethnicity while Case 2 is Brazilian. A total of six individuals within the two families were studied.ResultsCase 1 (original propositus of the syndrome) has the characteristic developmental rod/cone abnormality with large amplitude electroretinogram responses and no retinal degeneration. She was homozygous for a novel mutation, c.[del196–201del6] (p.G66-C67del), which lies entirely within the P-box for this gene. By comparison, Case 2 had Goldmann-Favre Syndrome with retinal degeneration and low electroretinogram signals. She was a compound heterozygote for c.[119–2A>C]+[del194–202del9] (p.N65-C67del), mutations that have been reported previously. Her second mutation overlaps that of Case 1 within the P-box.ConclusionsThe novel in-frame homozygous deletion of Case 1, within the P-box motif of the DNA binding domain, caused a developmental abnormality without retinal degeneration. Case 2, with more traditional Goldmann-Favre Syndrome with retinal degeneration, was a compound heterozygote where one allele had a similar P-box deletion but the other was a splicing defect. Case 1 is the first reported homozygous deletion within the P-box. This is the first report of NR2E3 mutations in a Persian and a Brazilian family

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Long-lasting effects of anti-VEGF/photodynamic combination therapy in the treatment of exudative age-related macular degeneration: a retrospective chart review

PURPOSE: To examine the potential long-term benefit of an anti-VEGF/photodynamic therapy (PDT) combination on patients treated for wet age-related macular degeneration (AMD). METHODS: A retrospective chart review was conducted on 29 eyes (subjects) from 26 patients (eight male and 18 female) that showed sustained, positive response to combination therapy for exudative AMD for a minimum of 1 year. Collected data included: visual acuity, central retinal thickness, intraocular pressure and history of glaucoma, wet AMD onset and treatment history, concomitant use of anticoagulants and past history or development of cerebrovascular or cardiovascular disease while receiving combination therapy. RESULTS: Subjects underwent an average of five injections and two PDT treatments in total over 16 months before the choroidal neovascular membrane (CNVM) stabilized and became inactive for at least 1 year. Prior to the effective anti-VEGF/PDT combination therapy the median Snellen visual acuity ranged from 20/200 to 20/250 and presented at no worse than 20/200 at 1 year after treatment. Some subjects were followed for up to 5 years and remained inactive. CONCLUSION: Combination therapy can cause long-lasting closure of the CNVM, even with advanced disease resistant to anti-VEGF monotherapy

From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus

Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures) and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells). We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping), failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial) place learning into navigational performance

The Cryptococcus neoformans transcriptome at the site of human meningitis.

Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human host has not been attempted. Here, we extracted RNA from yeast cells taken directly from the cerebrospinal fluid (CSF) of two AIDS patients with cryptococcal meningitis prior to antifungal therapy. The patients were infected with strains of C. neoformans var. grubii of molecular type VNI and VNII. Using RNA-seq, we compared the transcriptional profiles of these strains under three environmental conditions (in vivo CSF, ex vivo CSF, and yeast extract-peptone-dextrose [YPD]). Although we identified a number of differentially expressed genes, single nucleotide variants, and novel genes that were unique to each strain, the overall expression patterns of the two strains were similar under the same environmental conditions. Specifically, yeast cells obtained directly from each patient's CSF were more metabolically active than cells that were incubated ex vivo in CSF. Compared with growth in YPD, some genes were identified as significantly upregulated in both in vivo and ex vivo CSF, and they were associated with genes previously recognized for contributing to pathogenicity. For example, genes with known stress response functions, such as RIM101, ENA1, and CFO1, were regulated similarly in the two clinical strains. Conversely, many genes that were differentially regulated between the two strains appeared to be transporters. These findings establish a platform for further studies of how this yeast survives and produces disease

New adhesive systems based on functionalized block copolymers

The goal of this work was to evaluate chemically-functionalized block copolymers as adhesion promoters for metal/thermoset resin interfaces. Novel block copolymers were synthesized which contain pendant functional groups reactive toward copper and epoxy resins. In particular, imidazole and triazole functionalities that chelate with copper were incorporated onto one block, while secondary amines were incorporated onto the second block. These copolymers were found to self-assemble from solution onto copper surfaces to form monolayers. The structure of the adsorbed monolayers were studied in detail by neutron reflection and time-of-flight secondary ion mass spectrometry. The monolayer structure was found to vary markedly with the solution conditions and adsorption protocol. Appropriate conditions were found for which the two blocks form separate layers on the surface with the amine functionalized block exposed at the air surface. Adhesion testing of block copolymer-coated copper with epoxy resins was performed in both lap shear and peel modes. Modest enhancements in bond strengths were observed with the block copolymer applied to the native oxide. However, it was discovered that the native oxide is the weak link, and that by simply removing the native oxide, and then applying an epoxy resin before the native oxide can reform, excellent bond strength in the as-prepared state as well as excellent retention of bond strength after exposure to solder in ambient conditions are obtained. It is recommended that long term aging studies be performed with and without the block copolymer. In addition, the functionalized block copolymer method should be evaluated for another system that has inherently poor bonding, such as the nickel/silicone interface, and for systems involving metals and alloys which form oxides very rapidly, such as aluminum and stainless steel, where bonding strategies involve stabilizing the native oxide

Land reclamation and artificial islands: Walking the tightrope between development and conservation

Coastal developments worldwide have put entire shoreline ecosystems at risk. Recently, land reclamation has been extended to the construction of whole new islands; a phenomenon that is particularly common in Asia and the Middle East and is recognised as a global conservation issue. Using Penang Island, Malaysia as a case study, we illustrate the relationship between rapid population growth and the simultaneous increase in urbanisation, land reclamation and extent of artificial shorelines; and decrease in the quality and extent of natural coastal habitats. Our goal was to provide an up-to-date assessment of the state of coastal habitats around Penang, identify knowledge gaps and identify locations that may be potentially suitable for eco-engineering. Comparisons of historical and current topographic maps revealed that land formerly consisting of coastal swamp and forest, mangrove forests, sandy beaches, and rubber and oil plantations have been lost to large-scale land reclamation and urbanisation. Between 1960 and 2015, there were increases in urbanised area, reclaimed land, and artificial shoreline extent. The total extent of mangrove forests has remained relatively stable but this balance is characterised by significant losses on the east coast coupled with increases on the west coast. Coastal development on the island is still on-going with plans for the construction of five artificial islands and another two coastal reclamation projects are either underway or scheduled for the near future. If the plans for future land reclamations are fully realized, 32.3 km2 of the 321.8 km2 island (10%) will be reclaimed land and the associated negative effects on the island’s natural coastal habitats will be inevitable. This study highlights sections of the coast of Penang Island in need of effective monitoring, conservation and management and explores the possibility of incorporating ecological engineering into development projects, either prospectively or retrospectively, to create more environmentally-friendly urban environments and to promote educational, amenity and economic activities. With coastal development taking place on a global scale, opportunities to balance development needs with conservation strategies abound and should be integrated into present and subsequent projects to protect these coastal ecosystems for future generations

Participation in environmental enhancement and conservation activities for health and well-being in adults: a review of quantitative and qualitative evidence

PUBHLT

Radiographic Alignment in Deformity Patients Treated With Personalized Interbody Devices: Early Experience From the COMPASS Registry.

BACKGROUND: Literature supports the need for improved techniques to achieve spinopelvic alignment and reduce complication rates in patients with adult spinal deformity (ASD). Personalized interbody devices were developed to address this need and are under evaluation in the multicenter Clinical Outcome Measures in Personalized aprevo (circle R superscript) Spine Surgery (COMPASS (TM suprascript) registry. This report presents interim COMPASS pre- and postoperative sagittal alignment results and complication rates for a subcohort of COMPASS patients diagnosed and surgically treated for spinal deformity. METHODS: COMPASS is a postmarket observational registry of patients enrolled either before or after index surgery and then followed prospectively for 24 months. Sagittal alignment was assessed with SRS-Schwab modifiers for pelvic incidence minus lumbar lordosis, pelvic tilt, and T1 pelvic angle. Summed SRS-Schwab modifiers were utilized to assign overall deformity status as mild, moderate, or severe. Complications were extracted from patient medical records. RESULTS: The study included 67 patients from 9 centers. Preoperative severe deformity was observed in 66% of patients. Index surgeries included implantation of a median of 2 personalized interbody devices by anterior, lateral, or transforaminal approaches and with a median of 8 posteriorly instrumented levels. Overall postoperative sagittal alignment improved with a significant decrease in the mean sum of SRS-Schwab modifiers that correlated strongly to improvements in pelvic incidence minus lumbar lordosis. Among 44 patients with preoperative severe overall deformity, 16 improved to moderate and 9 to mild deformity. Complications occurred for 13 patients (19.4%), including 1 mechanical complication requiring revision 9 months after surgery and none related to personalized interbody devices. CONCLUSIONS: This study demonstrates that ASD patients whose treatment included personalized interbody devices can obtain favorable postoperative alignment status comparable to published results and with no complications related to the personalized interbody devices. CLINICAL RELEVANCE: This study contributes to growing evidence that personalized interbody devices contribute to improved sagittal alignment in ASD patients by directly adjusting the orientation of adjacent vertebra

Shape change along geodesics with application to cleft lip surgery

Continuous shape change is represented as curves in the shape space. A method for checking the closeness of these curves to a geodesic is presented. Three large databases of short human motions are considered and shown to be well approximated by geodesics. The motions are thus approximated by two shapes on the geodesic and the rate of progress along the path. An analysis of facial motion data taken from a study of subjects with cleft lip or cleft palate is presented that allows the motion to be considered independently from the static shape. Inferential methods for assessing the change in motion are presented. The construction of predicted animated motions is discussed