bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for an initial central scotoma compared with an initial peripheral scotoma
Authors: CHO B , KANG JW , PARK BJ
Published: August 2014

Purpose To investigate the risk factors for an initial central scotoma (ICS) compared with an initial peripheral scotoma (IPS) in normal tension glaucoma (NTG).

Methods Sixty NTG patients (60 eyes) with an ICS and 106 NTG patients (106 eyes) with an IPS were included. Retrospectively, the differences were assessed with baseline characteristics, ocular factors, systemic factors, and life style factors between two groups. Also, the parameters of visual field were compared between two groups. Clinical characteristics and various systemic factors were analyzed between the 2 groups.

Results Patients from both ICS and IPS groups were of similar age, gender, family history of glaucoma, and follow‐up periods. Frequency of disc hemorrhage was significantly higher among patients with an ICS than in patients with an IPS (p<0.001). Moreover, systemic risk factors such as hypotension, migraine, Raynaud’s phenomenon, and snoring were more prevalent in the ICS group than in the IPS group (p<0.001, p=0.002, p= 0.007, p= 0.009, respectively). There were no statistically differences in lifestyle risk factor such as smoking or body mass index. Pattern standard deviation was significantly greater in the ICS group than in the IPS group (p=0.005), but the mean deviation was similar between the 2 groups (p=0.096).

Conclusion NTG patients with ICS and IPS have different profiles of risk factors and clinical characteristics. This suggests that the pattern of initial VF loss may be useful to identify patients at higher risk of central field loss.
Intraocular pressure dynamics during one year followup after phacotrabeculectomy versus trabeculectomy for primary open angle glaucoma
Authors: POPA CHERECHEANU A , COMAN C , PIRVULESCU R , DASCALU AM , GEAMANU A , STANA D , DUTA S , GRADINARU S , IANCU R
Published: August 2014

Purpose Maintaining intraocular pressure in range of target values interval is one of the desiderates of antiglaucoma surgery. Intraocular pressure (IOP) variations occur after trabeculectomy or phacotrabeculectomy. The aim of our study is to provide data regarding the magnitude of these variations during one year following the surgical interventions mentioned above.

Methods This is a study assessing two groups, one comprising of 28 patients that underwent trabeculectomy with 5‐fluorouracil and the other comprising of 26 patients that underwent phacotrabeculectomy with 5‐fluorouracil. All patients had surgery for uncontrolled primary open angle glaucoma. The IOP was monitored using Goldmann aplanotonometry 1 day, 1 week, 1 month, 3 months, 6 months and 1 year postoperative.

Results The difference between the mean IOP after 1 year and the preoperative IOP was statistically significant in both groups (9.41 +/‐4,32 mmHg, 42% reduction in trabeculectomy group, p value 4.45x10‐19 and 8.03+/‐5,17 mmHg, 34% reduction in phacotrabeculectomy group, p value 1.46x10‐9) and the mean IOP was significantly reduced at all time points in both groups.

Conclusion IOP was statistically significant reduced after surgery in both groups. The maximal variation occurred after phacotrabeculectomy, with the highest magnitude in the first 6 months after surgery. In the following 6 months, IOP did not change statistically significant after either phacotrabeculectomy or trabeculectomy.
Choroidal detachment in post trabeculectomy patients in an asian tertiary eye centre
Authors: XU YP , YIP WLL , YONG KYV , LIM BA , WONG HT , GAN N
Published: August 2014

Purpose The aim of this study is to identify risk factors that lead to choroidal effusion in post trabeculectomy patients.

Methods The clinical notes of all patients who developed choroidal detachment after trabeculectomy for glaucoma between 2000 to 2011 in a tertiary institution were reviewed. Potential risk factors including glaucoma subtype, intraoperative complications, ischemic risk factors, use of anti‐metabolites and post‐operative procedures were analysed as potential risk factors.

Results Twenty‐three subjects developed post‐trabeculectomy choroidal detachments. The mean age was 70.8 +/‐ 12 years (range 38 to 86 years old). 17 out of the 23 choroidal detachments were male patients. The most common subtype of glaucoma associated with choroidal detachment was primary open angle glaucoma. 2 patients (8.7%) developed choroidal detachments within 1 week post‐operatively. The hypotony lasted 2 weeks to 48 months with 4 patients (17.4%) requiring revision of the bleb. All patients had adjunctive anti‐metabolites used, with MMC used in 22 cases and 5FU used in 1. 4 patients (17.4%) had diabetes, 6 (26.0%) had hyperlipidemia, 11 (47.8%) had hypertension and 2 (8.7%) were smokers. The mean final visual outcome was 0.30 on the logMAR scale.

Conclusion All patients had good visual outcomes. Of the factors analysed, use of anti‐metabolites was the only one found to be associated with development of choroidal detachment post‐trabeculectomy. Vast majority of choroidal detachments occur beyond 2 weeks after surgery and clinicians should continue to monitor these patients carefully.
Efficacy and safety of anti TNFα in non‐infectious uveitis: a multi‐center retrospective study
Authors: BIDAUT GARNIER M , VALLET H , SEVE P , HERON E , PERLAT A , TIEULIE N , PERARD L , LEHOANG P , SAADOUN D , BODAGHI B
Published: August 2014

Purpose TNF‐α inhibitors have been used over the last few years in noninfectious uveitis refractory to traditional immunosuppressive agents, with promising results. However, in the literature, TNF‐α blockers have mostly been studied in uncontrolled trials, or case‐series with small effectives. The purpose was to evaluate the efficacy and safety of anti TNF‐α in a larger effective of patients.

Methods Evolution of noninfectious uveitis in patients treated with anti TNF‐α agents was retrospectively reviewed, for subjects managed of between July 2001 and June 2013 in ten French departments of ophthalmology. Ocular inflammation, dosage of prednisone were the main criteria for efficacy.

Results We included 162 patients. Uveitis was bilateral in 82%, panuveitis in 62%, with retinal vasculitis in35% and macular edema in54% of cases. Anti TNFα (infliximab 57%, adalimumab 40%, etanercept 3%) were introduced in case of non‐response to immunosuppressives in 88%. Median duration of treatment was 18 months [8‐33] and median follow up, 27 months [8‐53]. Complete or partial response was reported in 93.2% of subjects at 1 month. Mean dose of prednisone was significantly reduced after 6 and 12 months of treatment (n=101 ; 15mg [6‐47,5] at introduction vs 10mg [8‐15] at 6 months and 9mg [5‐15] at 12 months; p<0,0001). Side effects were observed in 32 patients (n=130; 25%); they were severe in 3 cases (1 lymph node tuberculosis and 2 angioedema). Side effects came from infliximab rather than adalimumab (p<0.001).

Conclusion TNF‐α blockers seem to be safe and effective in reducing inflammation with further tapering of corticosteroids, in severe cases of noninfectious uveitis.
Comparative immunological study of of lamellar and penetrating keratoplasty in murine model
Authors: LEE HS , CHOI MINY , JOO CHOUN
Published: August 2014

Purpose Lamellar keratoplasty (LK) has been considered an acceptable alternative surgery for penetrating keratoplasty (PKP), because LK has the advantage of lower risk of graft rejection and intraocular complications, according to recent clinical outcomes. But the relative immunological mechanism of graft rejections for the two procedures is uncertain. We have developed a murine model of lamellar keratoplasty to try to understand the immunological mechanisms of those two procedures.

Methods We have developed a murine model of lamellar keratoplasty to try to understand the immunological mechanisms of those two procedures through real‐time PCR, immunohistochenistry, and flow cytometric analysis.

Results LK mice showed less graft rejection than PK mice and LK led to less DTH response and IFN‐γsecretion in vitro recall assay of T cells from drainage lymph nodes, as compared to PK (acceptance; acc). Corneal expression of IL‐1β and IFN‐γ in PKacc were significantly increased later. In addition, LK showed less angiogenesis and lymphangiogenesis in grafted cornea than PK, and LK led to decreased number of MHCIIhighCD11c+ antigen presenting cells(APCs) in the draining LNs.

Conclusion In conclusion, these results show that LK presents less graft rejection than PK through lower angiogenesis and lymphangiogenesis, which could make pathologic T cells and APC less migration into drainage LNs and grafted corneas, respectively.
Comparative analysis of two ocular endothelial cells
Authors: MAMMADZADA P , GUDMUNDSSON J , KVANTA A , ANDRE H
Published: August 2014

Purpose In the eye, angiogenesis is associated with many pathological conditions. Retinal and choroidal endothelial cells (RE and CE cells) are the main cellular components of ocular angiogenesis. It is widely accepted that endothelial cells (EC) from different vascular beds show heterogeneity. Comparative study of RE and CE cells can lead to deeper understanding of the mechanisms through which EC become activated to undergo pathologic behaviors. Therefore, the goal of the study was isolation, cell culturing, and characterization of human CE and RE cells, and comparative analysis of these two cell lines.

Methods Human consented‐donor eyes were used for preparation of CE and RE cell cultures. The posterior segment of these eyes was microdissected into isolated tissues (retina and choroid). Isolation of RE and CE cells from these tissues was achieved by positive selection of endothelium by targeting CD31. Characterization of RE and CE cells was performed by immunostaining for EC specific markers (CD31, isolectin, and acetylated‐LDL uptake). Further analysis is achieved by qPCR.

Results Endothelial cells from the retina and the choroid have been specifically isolated and displayed high endothelial cell‐type purity. Both RE and CE cell cultures displayed positive staining for CD31 and isolectin, as well as acetylated‐LDL uptake; positive staining was confirmed to 100% of the cultured cells. Differences between RE and CE cells was not clear upon IF microscopy. Initial qPCR analysis has shown discreet variations between RE and CE cells.

Conclusion RE and CE cells exhibit similar morphologies and staining patterns for the specific endothelial cell markers studied. Extensive comparative analysis of these two ocular EC‐lines is undergoing by a series of qPCR arrays.
Exogenous regulation of the HIF pathway in RPE cells
Authors: ANDRE H , EKSTROM M , TAKEI A , MA Y , KVANTA A
Published: August 2014

Purpose To investigate the effects of a series of hypoxia‐inducible factors (HIF)‐regulating molecules (HRM) on the hypoxia pathway in retinal pigment epithelial (RPE) cells, critically involved in neovascular age‐related macular degeneration (nAMD) pathogenesis.

Methods ARPE‐19 cells were transfected with plasmids encoding FLAG‐tagged HRM, as well as HIF‐1α and HIF‐2α. Effects of HMR on ARPE‐19 were analyzed by a luciferase reporter assay (DLR), Western blot, and soluble vascular endothelial factor (VEGF)‐capture assay. Effects on endothelial cells (EC) were studied by exposing HUVEC cells to ARPE‐19 pre‐conditioned media after transfection with particular HRM.

Results The DLR denoted a marked negative regulation of HIF‐1α activity in ARPE‐19 in the presence of all PHDs. Analysis of HIF‐1α protein showed a very considerable decrease in the presence of PHD2, together with the most dramatic reduction of HIF‐1α protein life‐time. The immunoprecipitated level of VEGF from the media of ARPE‐19 cells transfected with PHD2 was considerably lower than that of an empty control. HUVEC proliferation was decreased in conditioned media from ARPE‐19 transfected with PHD2.

Conclusion PHD2 seems to be the most potent negative‐regulator of the HIF pathway. Furthermore, the negative effects of PHD2 were clearly associated with decrease in secreted VEGF and reduced EC proliferation. These results may have implications for the clinical treatment of patients with nAMD, particularly regarding the use of gene therapy to negatively regulate the neoangiogenesis present in these patients.
A prospective study of ocular manifestations in transthyretin‐related familial amyloid polyneuropathy
Authors: MENEY J , BARREAU E , MINCHEVA Z , CAUQUIL C , LABETOULLE M , ADAMS D , ROUSSEAU A
Published: August 2014

Purpose To study the prevalence and the clinical characteristics of ocular manifestations of transthyretin‐related familial amyloid polyneuropathy (TTR‐FAP).

Methods This prospective monocentric observational study was conducted at the french national reference center for TTR‐FAP. Genetically confirmed TTR‐FAP patients had a complete neurologic and ophthalmologic evaluation. Sensorimotor polyneuropathy (SPN)and vegetative neuropathy were staged. Ophthalmic examination included best corrected visual acuity (BCVA), Schirmer test, intraocular pressure (IOP), slit lamp photographs, gonioscopy, fundus examination, ultrasound pachymetry, and RNFL‐OCT. Automated perimetry was performed when necessary. Medical and surgical treatments were analysed for all patients.

Results Fifty seven patients (31 males and 26 females, aged 26‐83 years, mean 53.6±13.6 years, were included between 2011 and 2013. Patients were mainly of Portuguese origin (N=28; 49%). Val30Met mutation was present in 42 patients (73.7%). Ocular Hypertension (IOP>21mmHg) and glaucoma occurred in 11 patients (19.3%) and were associated with amyloid deposits in the anterior chamber with a "clamshell" pupil in 91.3% of cases. Amyloid vitreous deposits were present in 12 patients (21%) and had already required vitrectomy in 9 eyes of 5 patients. A BCVA of 20/200 or worse in one eye was found in 9 patients (15.8%) and was caused by secondary glaucoma in 66% of cases.

Conclusion In our series, amyloid glaucoma was exclusively found in carriers of the Val30Met mutation. OHT and glaucoma occurred more frequently in patients with autonomic neuropathy. Severe visual impairment was mainly caused by secondary glaucoma, and was associated with severe SPN.
Impact of age of myopia onset and parental myopia severity on the eventual myopia status in an individual
Authors: LIM SJ
Published: August 2014

Purpose To examine whether parental myopia and the age of myopia onset can predict the eventual severity of myopia for an individual. This will help decide whether a child needs treatment to slow myopia progression and the likely duration of treatment.

Methods All myopic Chinese students aged 17 to 19 years old from a school in Singapore, and their parents were invited to participate in this study. Each eligible student and both parents had a comprehensive ocular examination (Retinomax K‐Plus2; Nikon, Tokyo, Japan). Participants also completed a questionnaire on their age, sex, age of onset and stabilisation of myopia. Statistical analysis was performed using SPSS.

Results 59 female and 41 male eligible students and their biological parents were assessed. The individual’s age of myopia onset was moderately correlated (r=0.600) with his post‐stabilisation myopia status. Parental myopia severity was mildly associated with the individual’s myopia status (Pearson’s correlation(r)=0.337). The daughters’ myopia status correlated better with their mothers' than fathers', while that of sons' better with their fathers'. Despite a general trend of myopia severity being worse in females than males, a Z‐test showed that the means of myopia severity of the 2 groups were not significantly different, and a Chi‐square test showed that the individual’s myopia status is independent of parental myopia.

Conclusion The results suggest that for a Chinese myopic child in Singapore, a young age of myopia onset would be associated with a more severe eventual myopia status. Decision to prescribe drugs to slow myopia progression should be based on a young age of onset rather than family history, as this has a greater impact on eventual myopia status than parental myopia.
Interest of an ophthalmological consultation dedicated to the children presenting autism spectrum disorders
Authors: JANY B , MONTANARI S , BASSON W , JONQUA F , MILLE C , MILAZZO S
Published: August 2014

Purpose The children presenting Autism spectrum disorders (ASD) often present ophthalmological disorders. This is why, we plan an ophthalmological consultation dedicated to the children ASD with a partnership between the ophthalmology’s department and the “Centre Ressource Autisme” (CRA).

Methods The conditions of set up the consultation were: ‐ Training took place at the orthoptist’s formation and with the residents in ophthalmology to educate ‐ Some modifications in the ophthalmological consultation were performed : ‐ An adaptation of the consultation‘s site. ‐ Schedules of dedicated consultations ‐ An increased time of consultation with 2 examinations: first orthoptic and after, ophthalmologic. Every step of the exam is announced, the used equipments are gradually brought to the children who can watch and also touch them before the examination. ‐ A preparation for the consultation with the child may take place through the use of specific visual medias. ‐ The second or the third examination could be proposed if necessary

Results Fifteen children were examined in one year (year 2013) for whom an orthoptic examination, measurement of the objective refraction, the slit lamp examination and fundus were performed. Refractive errors and strabismus were detected or confirmed and a bilateral cataract was diagnosed and treated.

Conclusion This medical network allows to dedramatize of the ophthalmological examination of the children with ASD both the families and the medical professionals. It also has an interest in the training of orthoptists and residents. This type of care could develop and allow a better pathology’s detection.
Multifocal and toric implantation in a paediatric population: a retrospective study
Authors: HEITZ A , RITZ M , SAUER A , SPEEG‐SCHATZ C
Published: August 2014

Purpose The management of pediatric cataract is a therapeutic challenge. The aim of our study was to assess the potential benefits of the multifocal and toric lens implantation in the children depending on the age. The previous results of multifocal IOL in the child are encouraging but are derived from analyzes of children over 4 years. The toric implantation in the childhood was never studied.

Methods In this retrospective non‐randomized monocentric study, children with bilateral and unilateral cataract between 0 and 9 years with a visual acuity less than 0,3logMAR were implanted with multifocal IOL (or with a toric IOL when the corneal astigmatism was higher than 2 dioptries). Outcome measures of best corrected visual acuity (BCVA) for distance, distance‐corrected near visual acuity (DCNVA), contrast sensitivity, stereopsis and total astigmatism were analysed with the Student test in 2 age groups : less than 4 years (group 1) and more than 4 years (group 2).

Results 21 eyes of 16 children (mean age 5,05 years, from 9 months to 9 years) were included in the multifocal study, 3 eyes of 2 children were included in the toric study. Group 1 included 5 eyes (4 children), group 2 included 13 eyes (10 children). Both groups showed significant improvement in BCVA at one year follow‐up. Stereopsis was better in group 2 with unilateral implantation. The improvement of the DCNVA was significantly better in group 2 with unilateral implantation (0,38 logMAR, p<0,05). The total astigmatism, the BCVA and DCNVA were improved with a toric implantation, the stereopsis was similar.

Conclusion Multifocal IOL implantation is a viable option for the children more than four years with unilateral cataract. The toric implantation analysis needs further results.
The role of cerebrospinal fluid in optic disc pit maculopathy: a case report studied by enhanced depth imaging optical coherence tomography (EDI‐OCT)
Authors: MARTINEZ VELEZ M , ASCASO FJ , HUERVA V , CRISTOBAL J , ZABADANI K , ALMENARA C , HERRERA L , PEREZ NAVARRO I , CARAMELLO C
Published: August 2014

Purpose Optic disc pit(ODP) is a rare congenital optic disc abnormality characterized by a localized grayish‐white depression usually in the center or inferotemporal part of the optic nerve head. It is generally unilateral (85‐90%) and its prevalence is estimated to be 1 in 11,000. Unless the ODP develops maculopathy, patients remain asymptomatic. Serous macular detachment may occur in up to 50% of cases, leading to significant decrease in visual acuity. Although the pathogenesis of ODP maculopathy is unclear, various theories about its onset have implicated fluid entry either from the vitreous cavity or from leakage of cerebrospinal fluid through the peripapillary subarachnoid space. The aim of this study was to evaluate the source of subretinal fluid under the macula in a patient with ODP

Methods Enhanced depth imaging optical coherence tomography(EDI‐OCT) using the stars scan pattern of the Spectralis HRA + OCT (version 1.5.12.0; Heidelberg Engineering) was used

Results Horizontal SD‐OCT section revealed a small amount of intraretinal fluid in the outer nuclear layer and a prominent serous macular detachment at the same time but with no relationship with either the vitreous cavity or the subarachnoid space. However, a direct communication between the subretinal space and the peripapillary subarachnoid space through the ODP was demonstrated for the first time by using EDI‐OCT.

Conclusion This case supports the theory that the source of serous macular detachment in some ODP cases could be cerebrospinal fluid passing into the retina through the ODP due to an incomplete closure of the embryonic fissure
Choroidal thickness and volume in healthy children messured by enhanced depth imaging optical coherence tomography
Authors: HERRERA L , PEREZ NAVARRO I , CARAMELLO C , ZABADANI K , ALMENARA C , PÉREZ D , MARTINEZ M , SANCHEZ A , PINILLA I , ESTEBAN O
Published: August 2014

Purpose To evaluate choroidal thickness during childhood using enhanced depth imaging (EDI) spectral‐domain optical coherence tomography (SD‐OCT), and its correlation with age, sex, axial length (AL) and refractive error (RE)

Methods Cross‐sectional study in which 93 eyes of 93 healthy children were studied using a 25 A‐scans‐EDI SD‐OCT protocol. Choroidal thickness was segmented manually, and an ETDRS grid was applied to analyze choroidal thickness and volume in each of its nine sectors. Two observers independently studied 30 children to assess repeatability and reproducibility, using intraclass coefficient (ICC).

Results We included 50 males and 43 females, with mean age of 9.62±2.89 years, mean refractive error (spherical equivalent) +0.03±2.22D and mean axial length (AL) of 23.19±13mm. Mean subfoveal choroidal thickness (SFCT) and volume was 314.22 ±55.48, and 0.25±0.04m3, respectively. SFCT was significantly thicker in the hyperopic group (AL 22.39±0.83mm). There were no statistically significant differences between myopic (AL 24.33±0.76mm) and emmetropic (AL 23.27±0.54mm) children, as well as between males and females. There was a weak, positive correlation between SFCT and age (r=0.259, p=0.012). Inter and intra‐observer ICC of the nine sector of the ETDRS grid ranged from 0.929‐0.991 and 0.992‐0.998, respectively.

Conclusion Pediatric SFCT is greater in hyperopic children. The choroid appears to become thicker with age. Manual choroidal thickness segmentation by EDI SD‐OCT showed a high inter and intra‐observer repeatability
Prediction of Parkinson’s disease severity based on RNFL thickness evaluated by OCT
Authors: JIMENEZ DEL RIO B , ASCASO FJ , CRISTOBAL J , PÉREZ D , IBAÑEZ J , LÓPEZ DEL VAL J
Published: August 2014

Purpose To determine the relationship between peripapillary retinal nerve fiber layer (RNFL) thickness in Parkinson disease (PD) with the severity of this neurological disorder and to define a simple biomarker to predict clinical severity.

Methods Peripapillary RNFL thickness was measured in 102 eyes from 52 PD patients by using optical coherence tomography (OCT) and compared with 97 eyes from 50 age‐matched healthy controls. The Unified Parkinson's Disease Rating Scale (UPDRS) total score was used and responses in the ON medication state were measured.

Results PD patients showed a statistically significant decrease in average peripapillary RNFL thickness compared with control eyes (p<0.001). This reduction was observed in every quadrant: inferior (p<0.001), superior (p<0.001), nasal (p<0.001) and temporal (p=0.017) in PD patients. Furthermore, a strong inverse correlation was found between PD severity measured according to the UPDRS score with either the average peripapillary RNFL thickness (r= –0.615; p<0.001) or PD duration (r= –0.303; p=0.002). From these results, we defined the following regression equation, which is able to predict the UPDRS score from the mentioned variables: UPDRS = 81.6 + 29.6 * log PD duration (yr) – 0.6 * RFNL thickness (µm).

Conclusion As the evolution and severity of PD progress, the peripapillary RNFL thickness gradually diminishes. These results suggest that the average peripapillary RNFL thickness measured by OCT might be useful as a biomarker to detect the early onset and progression of PD.
A case report survey (CRS) on the natural history of visual acuity in patients with Leber’s hereditary optic neuropathy (LHON)
Authors: METZ G , COPPARD N , PETRAKI D , MEIER T , KLOPSTOCK T , SAHEL J
Published: August 2014

Purpose LHON is an inherited mitochondrial orphan disease leading to rapid, irreversible vision loss in the majority patients. This survey reports the clinical course of vision loss and recovery in patients with LHON based on a large retrospective data collection.

Methods Visual acuity (VA) data from 383 individual patients were collected by chart review conducted in 11 clinical centres under local ethics approval using a standardized VA report form. Change of VA with time since onset of symptoms was analysed using cross sectional and longitudinal data analyses. Mutation dependent rates for spontaneous clinically relevant recovery (off‐to‐on‐chart or at least 2 lines on chart) of VA were established from 774 individual observations available from 74 patients for whom relevant longitudinal VA data were available for up to 31 months.

Results The data confirm the expected rapid loss of VA with 73% of eyes deteriorating beyond the threshold for legal blindness within 3 months of onset. The VA nadir was typically reached within less than 6 months from onset and for observations available between 12 and 24 months from onset, 78% of eyes remained legally blind. The time to VA recovery and proportion of patients with recovery from nadir varied with the LHON‐associated mtDNA mutation carried. A total of 31.1% patients presented with spontaneous clinically relevant recovery G11778A: 25%, G3460A: 50%, T14484C: 43%).

Conclusion These data demonstrate that in patients with LHON vision loss is rapidly progressive and severe. The great majority of patients do not regain VA but remain legally blind.

Commercial interest
Mutational and clinical spectrum in Korean with Leber’s hereditary optic neuropathy
Authors: YUM HR , KIM MS , SHIN SY , PARK SH
Published: August 2014

Purpose To investigate the spectrum of mutations of mitochondrial DNA (mtDNA) and clinical features in Korean with Leber’s hereditary optic neuropathy (LHON).

Methods Total genomic DNA was isolated from the peripheral blood leukocytes of the patients who were suspicious of LHON. The presence of mutations were screened by direct sequencing were analyzed against mitochondrial reference sequence on genetic analyzer. The ophthalmologic examinations of patients were conducted, including visual acuity(VA), color vision, retinal nerve fiber layer(RNFL) thickness and visual field(VF).

Results Two primary mutations (G1778A, T14484C) and five secondary mutations (T3394C, C3497T, G11696A, A11392C, T14502C) were detected in 34 of 164 unrelated patients. Among the 34 patients, primary mutation was detected in 21 patients, secondary mutation in 11 patients, and combined primary and secondary mutation in 2 patients. Compared the patients with primary mutation, patients with secondary mutation had increased proportion of woman. The VA was significantly better in secondary mutation than primary mutation. Also, the severity of the color vision deficiency was significantly mild in secondary mutation relative to primary mutation. No significant difference was found in the OCT parameters between the groups including temporal area. However, the visual field index and mean deviation of the visual field test were different significantly between groups.

Conclusion Our results emphasize the possible heterogeneity of LHON‐associated mtDNA mutations and clinical phenotypes in Korean LHON patients. Candidate pathogenic mtDNA mutations including major primary mutations should be rigorously investigated.
Leber hereditary optic neuropathy and a new MT‐ND1 pathologic mutation
Authors: ESTEBAN O , MARTINEZ‐ROMERO I , HERRERO‐MARTIN MD , LLOBET L , EMPERADOR S , MARTIN‐NAVARRO A , NARBERHAUS B , ASCASO FJ , LOPEZ‐GALLARDO E , MONTOYA J , RUIZ‐PESINI E
Published: August 2014

Purpose Over 90% of Leber hereditary optic neuropathy (LHON) is caused by one of three mitochondrial DNA (mtDNA) mutations (m.11778A>G, m.3460G>A, m.14484T>C) in genes for respiratory complex I (CI) subunits. These mutations are homoplasmic and characterized by incomplete penetrance, and a large percentage of patients harboring these mutations have no family history of disease. However, the pathogenicity of these mutations has not been confirmed. We report a patient who exhibited typical clinical features of LHON and presented a new mutation in the MT‐ND1 gene and lacked all three of the most common mtDNA mutations.

Methods The diagnosis of LHON in our patient was based on clinical studies. The mtDNA was completely sequenced and the candidate mutation was analyzed in more than 18,000 individuals around the world, its conservation index was estimated in more than 3,100 species from protists to mammals, its position was modeled in the crystal structure of a bacteria ortholog subunit and its functional consequences were studied in a cybrid model.

Results Genetic analysis revealed an m.3472T>C transition in the MT‐ND1 gene that changes a phenylalanine to leucine at position 56. Bioinformatics, molecular‐genetic analysis and functional studies suggest that this transition is the etiologic factor for the disorder.

Conclusion The evidence presented strongly suggest that this new mutation expands the spectrum of deleterious changes in mtDNA‐encoded complex I polypeptides associated with this pathology and highlights the difficulties in assigning pathogenicity to new homoplasmic mutations that show incomplete penetrance in sporadic LHON patients.
Lower heart rate variability predicts increased level of C‐reactive protein 4 years later in healthy, nonsmoking adults
Authors: Jarczok M. N. , Koenig J. , Mauss D. , Fischer J. E. , Thayer J. F.
Published: August 2014

Background

Inflammation and vagally mediated heart rate variability (vmHRV) have been implicated in a number of conditions including diabetes and cardiovascular disease. Consistent with the inflammatory reflex termed the ‘cholinergic anti‐inflammatory pathway’, numerous cross‐sectional studies have demonstrated negative associations between vmHRV and inflammatory markers such as C‐reactive protein (CRP). The only prospective study, however, showed the opposite: higher CRP at baseline predicted higher high‐frequency heart rate variability (HF‐HRV) at follow‐up. Thus, additional studies are needed to examine the prospective association between vmHRV and CRP.

Methods

Healthy employees participated in a voluntary on‐site health assessment. Blood samples and ambulatory heart rate recordings were obtained, and night‐time HF‐HRV was calculated. Useable heart rate data were available in 2007 for 106 nonsmoking employees (9% women; age 44.4 ± 8 years), all of whom returned for an identical follow‐up health assessment in 2011. Bootstrapped (500 replications) bivariate (r) and partial Pearson's correlations (ppc) adjusting for sex, age and body mass index at baseline (2007) were calculated.

Results

Zero‐order correlations indicated that higher HF‐HRV was associated with lower levels of CRP at both time‐points (2007: r = −0.19, P < 0.05; 2011: r = −0.34, P < 0.001). After adjustment, HF‐HRV remained a significant predictor of CRP (ppc = −0.20, P < 0.05).

Conclusion

In this study, we have provided in vivo support for the cholinergic anti‐inflammatory pathway in humans. Cardiac vagal modulation at baseline predicts level of CRP 4 years later. Our findings have important implications for the role of vmHRV as a risk factor for cardiovascular disease morbidity and mortality. Interventions targeted at vmHRV might be useful in the prevention of diseases associated with elevated systemic inflammation.
A Twin Study of Objective and Subjective Pubertal Timing and Peer Influence on Risk‐Taking
Authors: Kretsch Natalie , Mendle Jane , Harden Kathryn Paige
Published: August 2014

This study used a behavioral genetic design to test whether three measures of pubertal timing moderated peer influence on risk‐taking in a sample of 248 female adolescent twin pairs (Mage = 16.0,SD = 1.5) from the National Longitudinal Study of Adolescent Health. Peer influence was operationalized as the quasi‐causal association between girls' self‐reported risk‐taking and the risk‐taking reported by their friends. Girls with earlier ages at menarche and who perceived themselves as more developed than peers were more susceptible to peer influence on risk‐taking. However, age‐standardized ratings of body changes did not moderate peer influence. This study highlights distinctions between multiple measures of pubertal timing, using an innovative synthesis of genetically informative data and peer nomination data.
Low prevalence of hepatitis B virus infection in patients with autoimmune diseases in a Chinese patient population
Authors: Sui M. , Wu R. , Hu X. , Zhang H. , Jiang J. , Yang Y. , Niu J.
Published: August 2014

Hepatitis B is a very common communicable disease in China but the prevalence of hepatitis B virus (HBV) infection in patients with autoimmune diseases is unknown. We retrospectively investigated the prevalence of autoimmune diseases in patients with HBV infection. The medical records of 4060 patients with autoimmune or nonautoimmune diseases were reviewed. A positive test result for hepatitis B surface antigen (HBsAg) was used to indicate the presence of HBV infection. Autoimmune diseases included autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and ulcerative colitis. Nonautoimmune conditions included inguinal hernia, appendicitis and pregnant or postpartum women. The proportion of autoimmune disease patients who were HBsAg positive (2.24%) was significantly lower than that of nonautoimmune disease patients who were HBsAg positive (4.58%; P = 0.0014). Regarding hepatic autoimmune diseases, the positivity rates for HBsAg in autoimmune hepatitis patients (0.83%) and primary biliary cirrhosis patients (1.02%) were both significantly lower than in nonautoimmune patients (4.58%; P = 0.006 and 0.004, respectively). Patients with hepatic autoimmune disease were significantly less likely to be HBsAg positive (0.93%) than patients with non‐hepatic autoimmune disease (3.99%; P = 0.002). Patients with autoimmune diseases, especially those with hepatic autoimmune disease, may more efficiently clear HBV than patients with nonautoimmune diseases.
Context Effects in the Processing of Phonolexical Ambiguity in L2
Authors: Chrabaszcz Anna , Gor Kira
Published: August 2014

In order to comprehend speech, listeners have to combine low‐level phonetic information about the incoming auditory signal with higher‐order contextual information to make a lexical selection. This requires stable phonological categories and unambiguous representations of words in the mental lexicon. Unlike native speakers, second language (L2) speakers, who perceive nonnative sounds through the prism of their first language (L1), operate with fuzzy phonological categories, which lead to phonologically ambiguous lexical representations (e.g., the words rock and lock can be confused if phonological representations for /r/ and /l/ are not sufficiently robust). The present study uses the AX discrimination task to establish the degree of sensitivity of L2 listeners to the Russian hard/soft phonological contrast. The same phonological contrasts are then used in the stimuli for the second task—listening comprehension task with word identification—to mark semantic, syntactic, and morphological distinctions in words. The goal of the study is to examine the contributions and relative efficiency of different contextual constraints (semantic, syntactic, and morphological) to the resolution of phonolexical ambiguity in L2 auditory sentence processing. The results suggest that when L2 phonological contrasts present a discriminability problem and create phonolexical ambiguity, L2 listeners rely on morphological constraints for disambiguation of word forms and syntactic constraints for disambiguation of words belonging to different parts of speech to a greater extent than on semantic constraints for disambiguation of nouns in the same form.
The Perception of Fluency in Native and Nonnative Speech
Authors: Bosker Hans Rutger , Quené Hugo , Sanders Ted , de Jong Nivja H.
Published: August 2014

Where native speakers supposedly are fluent by default, nonnative speakers often have to strive hard to achieve a nativelike fluency level. However, disfluencies (such as pauses, fillers, repairs, etc.) occur in both native and nonnative speech and it is as yet unclear how fluency raters weigh the fluency characteristics of native and nonnative speech. Two rating experiments compared the way raters assess the fluency of native and nonnative speech. The fluency characteristics were controlled by using phonetic manipulations in pause (Experiment 1) and speed characteristics (Experiment 2). The results show that the ratings of manipulated native and nonnative speech were affected in a similar fashion. This suggests that there is no difference in the way listeners weigh the fluency characteristics of native and nonnative speakers.
Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala
Authors: Hari Dass Shantala Arundhati , Vyas Ajai
Published: August 2014

Male rats (Rattus novergicus) infected with protozoan Toxoplasma gondii relinquish their innate aversion to the cat odours. This behavioural change is postulated to increase transmission of the parasite to its definitive felid hosts. Here, we show that the Toxoplasma gondii infection institutes an epigenetic change in the DNA methylation of the arginine vasopressin promoter in the medial amygdala of male rats. Infected animals exhibit hypomethylation of arginine vasopressin promoter, leading to greater expression of this nonapeptide. The infection also results in the greater activation of the vasopressinergic neurons after exposure to the cat odour. Furthermore, we show that loss of fear in the infected animals can be rescued by the systemic hypermethylation and recapitulated by directed hypomethylation in the medial amygdala. These results demonstrate an epigenetic proximate mechanism underlying the extended phenotype in the Rattus novergicus–Toxoplasma gondii association.
Influence of gene flow on divergence dating – implications for the speciation history of Takydromus grass lizards
Authors: Tseng Shu‐Ping , Li Shou‐Hsien , Hsieh Chia‐Hung , Wang Hurng‐Yi , Lin Si‐Min
Published: August 2014

Dating the time of divergence and understanding speciation processes are central to the study of the evolutionary history of organisms but are notoriously difficult. The difficulty is largely rooted in variations in the ancestral population size or in the genealogy variation across loci. To depict the speciation processes and divergence histories of three monophyletic Takydromus species endemic to Taiwan, we sequenced 20 nuclear loci and combined with one mitochondrial locus published in GenBank. They were analysed by a multispecies coalescent approach within a Bayesian framework. Divergence dating based on the gene tree approach showed high variation among loci, and the divergence was estimated at an earlier date than when derived by the species‐tree approach. To test whether variations in the ancestral population size accounted for the majority of this variation, we conducted computer inferences using isolation‐with‐migration (IM) and approximate Bayesian computation (ABC) frameworks. The results revealed that gene flow during the early stage of speciation was strongly favoured over the isolation model, and the initiation of the speciation process was far earlier than the dates estimated by gene‐ and species‐based divergence dating. Due to their limited dispersal ability, it is suggested that geographical isolation may have played a major role in the divergence of these Takydromus species. Nevertheless, this study reveals a more complex situation and demonstrates that gene flow during the speciation process cannot be overlooked and may have a great impact on divergence dating. By using multilocus data and incorporating Bayesian coalescence approaches, we provide a more biologically realistic framework for delineating the divergence history of Takydromus.
Reproducibility of Microvascular Vessel Density Analysis in Sidestream Dark‐Field‐Derived Images of Healthy Term Newborns
Authors: van den Berg Victor J. , van Elteren Hugo A. , Buijs Erik A. B. , Ince Can , Tibboel Dick , Reiss Irwin K. M. , de Jonge Rogier C. J.
Published: August 2014

Objective

Microcirculatory visualization has already been used to investigate buccal and cutaneous microcirculatory alterations in neonates. Still, the reproducibility of these microvascular measurements has never been studied in (premature) neonates. This study aimed to determine the reproducibility of microvascular vessel density in cutaneous and buccal SDF clips in one‐day‐old term newborns.

Methods

Buccal and cutaneous microcirculations were measured using SDF imaging. Vessel density was independently assessed by two investigators. Reproducibility was assessed from the ICC and Bland–Altman analysis.

Results

Reproducibility of vessel density assessment in the buccal area was good, with ICCs for total and PVD of 0.93 (0.88–0.97) and 0.93 (95% CI 0.85–0.97), respectively, and a near zero bias and acceptable limits of agreement in the Bland–Altman analysis. Reproducibility of assessment of the cutaneous microcirculation was poor with ICCs for total and PVD of 0.31 (0–0.70) and 0.37 (0–0.74), respectively, and large biases (3.09 and 2.53) in the Bland–Altman analysis.

Conclusions

Evaluation of buccal microvascular vessel density in SDF‐derived images in term newborns is reproducible in contrary to the cutaneous vessel density.
Telomere‐centric genome repatterning determines recurring chromosome number reductions during the evolution of eukaryotes
Authors: Wang Xiyin , Jin Dianchuan , Wang Zhenyi , Guo Hui , Zhang Lan , Wang Li , Li Jingping , Paterson Andrew H.
Published: August 2014

Whole‐genome duplication (WGD) is central to the evolution of many eukaryotic genomes, in particular rendering angiosperm (flowering plant) genomes much less stable than those of animals.

Following repeated duplication/triplication(s), angiosperm chromosome numbers have usually been restored to a narrow range, as one element in a ‘diploidization’ process that re‐establishes diploid heredity.

In several angiosperms affected by WGD, we show that chromosome number reduction (CNR) is best explained by intra‐ and/or inter‐chromosomal crossovers to form new chromosomes that utilize the existing telomeres of ‘invaded’ and centromeres of ‘invading’ chromosomes, the alternative centromeres and telomeres being lost. Comparison with the banana (Musa acuminata) genome supports a ‘fusion model’ for the evolution of rice (Oryza sativa) chromosomes 2 and 3, implying that the grass common ancestor had seven chromosomes rather than the five implied by a ‘fission model.’

The ‘invading’ and ‘invaded’ chromosomes are frequently homoeologs, originating from duplication of a common ancestral chromosome and with greater‐than‐average DNA‐level correspondence to one another. Telomere‐centric CNR following recursive WGD in plants is also important in mammals and yeast, and may be a general mechanism of restoring small linear chromosome numbers in higher eukaryotes.
King–Devick test normative reference values for professional male ice hockey players
Authors: Vartiainen M. V. , Holm A. , Peltonen K. , Luoto T. M. , Iverson G. L. , Hokkanen L.
Published: August 2014

The King–Devick (K‐D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K‐D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012–2013 and 2013–2014. Their average age was 23.8 years (median = 22.0 years, range = 16–40 years). The average K‐D score was 40.0 s (SD = 6.1 s, range = 24.0–65.7 s). K‐D test performance showed no association with age, education, or the number of self‐reported previous concussions in this sample. The association between trials 1 and 2 of the K‐D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K‐D test for professional male ice hockey players are reported. K‐D test performance did not vary by age, education, or concussion history in this study.
The Decline of Daily Newspapers and the Third‐Person Effect
Authors: Johnson Martin , Goidel Kirby , Climek Michael
Published: August 2014

Objective

In this article, we investigate the third‐person effect within the context of the decision by the New Orleans Times‐Picayune in September 2012 to end daily print circulation in favor of a three‐day‐per‐week publication schedule and online news offerings.

Methods

We utilize original survey data based on 1,043 telephone interviews with respondents living in the greater New Orleans area, including 530 landline respondents selected via random digit dialing and 513 respondents randomly selected from available cellular telephone blocks.

Results

We find evidence of a third‐person effect on judgments about changes at The Times‐Picayune. New Orleans area residents worry that the decline of information will negatively affect the ability of others to keep up with the news. We also show that the effects are contingent upon physical location. The greater the distance from New Orleans, the more pronounced concerns are about the effect of the loss of this daily information source on others in the community.

Conclusions

To date, third‐person effects have generally been studied within the context of enduring and established forms of communication, especially those viewed as having potential negative effects—politically biased messages, other forms of propaganda, and communication that could harm reputations. In this article, we extend this work to show third‐person effects persist within the context of declining news coverage.