bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in onset between eyes in patients with Leber's hereditary optic neuropathy (LHON)
Authors: Liu H. , La Morgia C. , Di Vito L. , Nazarali S. , Gauthier I. , Syed M. , Chahal J. , Ammar M. , Carbonelli M. , De Negri A.M. , Sadun A. , Carelli V. , Karanjia R. 
Published: September 2017

PurposeLeber's hereditary optic neuropathy (LHON) is an inherited mitochondrial disease characterized by a painless, subacute loss of central vision with over 95% of affected patients harbouring one of three mitochondrial DNA (mtDNA) classical point mutations (m.11778G>A, m.3460G>A and m.14484T>C). The purpose of this study was to compare the age of disease onset and time interval between affected eyes by mutation.MethodsAge of onset, unilateral versus bilateral presentation, interval between the first and second eye, and the mtDNA mutation were retrieved from two separate database registries consisting of 268 Italian and 71 U.S. patients.ResultsClinical data from 300 LHON patients with classical LHON mutations were evaluated (m.11778G>A, n = 216; m.3460G>A, n = 40; m.14484T>C, n = 44. Bilateral eye involvement was clinically documented in 99.4% of cases with 50.3% of all patients demonstrating sequential onset. In these latter cases the median inter‐eye delay was 12.8 weeks. Comparing the age of onset across mutation subtypes, the m.14484T>C mutation resulted in the lowest age at onset (19.2 ± 10.6 years) compared to m.11778G>A (25.8 ± 15.3 years) and m.3460G>A (20.9 ± 14.5 years) (p < 0.05). Interestingly, the m.14484T>C mutation exhibited more simultaneous than sequential onsets compared with the other two mutation subtypes (p < 0.001). Moreover, m.14484T>C showed a shorter and more reproducible interval between eyes (inter‐eye onset range = 1–44 weeks) versus m.11778G>A (range = 1–2016 weeks) and m.3460G>A (range = 2–816 weeks) for sequential presentations.ConclusionsThe m.14484T>C mutation, though least penetrant, manifested at an earlier age and resulted in a smaller inter‐eye delay interval range and higher incidence of simultaneous involvement compared to the other two classical mutations in LHON.
Clinical experience with idebenone in the treatment of patients harboring rare mutations related to Leber's hereditary optic neuropathy (LHON)
Authors: Llòria X. , Catarino C. , Downes S. , Vincent A. , Matloob S. , Silva M. , Klopstock T. 
Published: September 2017

PurposeLHON is a mitochondrial disease resulting in progressive, severe central vision loss, which in >95% of patients is characterized by 1 of 3 primary mitochondrial DNA mutations. However, further rare mutations have also been identified. To date the only treatment approved for LHON is idebenone, which is safe and effective at a dose of 900 mg/day; however, there is little information about its use in patients with rare mutations.MethodsThe Expanded Access Program (EAP) assessed idebenone's therapeutic potential in patients with onset of symptoms within 1 year prior to enrollment, in a real‐world setting. Efficacy was assessed as clinically relevant recovery (CRR) or clinically relevant stabilization (CRS). CRR is defined as improvement from off‐chart to reading 5 letters on the ETDRS chart, or as an improvement of 10 letters. CRS is defined as maintenance of VA <1.0 logMAR (20/200).ResultsOf 111 patients, 7 carried a rare mutation (A14495G, C3461T, G13051A, G3958A, T14487C, T4216C and T11253C+A14970G). The median age was 16.7 years, 57% were female and the time since onset was 2.8 months at the start of treatment. Patients presented with best visual acuity (VA) from 0.2 to 1.3 logMAR, and 3 patients presented with both eyes <1.0 logMAR at baseline (BL). One patient had only BL data currently available while 6 provided follow‐up data, with a median treatment duration of 9.2 months at last observation. All 6 experienced a CRR (10/12 eyes total) and the range for magnitude of recovery was between 2 and 13 lines on the ETDRS chart. The 2 eyes which did not experience CRR maintained VA <1.0 logMAR at last observation.ConclusionsLHON patients harboring rare mitochondrial mutations who received early treatment with idebenone presented with moderate VA loss at BL and experienced a very favorable outcome. All patients showed recovery of vision.
Optical coherence tomography angiography of the peripapillary retina and optic nerve head in Wolfram syndrome
Authors: Hassairi A. , Falfoul Y. , Matri K. , Regai E. , Chebil A. , El Matri L. 
Published: September 2017

PurposeTo evaluate the peripapillary and optic nerve head (ONH) microcirculation in patients affected by Wolfram syndrome and to correlate the results with the functional and anatomical conventional imaging: visual field (VF) and structural optical coherence tomography (OCT).MethodsThis study reports two cases of siblings with wolfram syndrome. They underwent a complete ophthalmological examination and an automated perimetry. A measure of peripapillary retinal nerve fiber layer (RNFL) thickness using a Swept‐ Source OCT was performed. Optical coherence tomography angiography (OCT‐A) images were obtained using a Swept‐Source DRI OCT Triton (Topcon Corporation, Japan). The scan size of optic disc area was 6 mm × 6 mm and he was divided into four layers, which were optic nerve head (ONH), vitreous, radial peripapillary capillary (RPC), and choroid layers. Peripapillary and nerve head vessels density were evaluated.ResultsThe first case is a 57 years old female patient with a history of diabetes insipidus and deafness, suffering from bilateral progressive visual loss. On fundoscopic examination, she had bilateral optic atrophy. Her visual acuity was reduced to 0.4 on both eyes. Her visual fields demonstrated generalized constriction. There was a family history of similar conditions. Her brother, a 46 years old male has a similar course of disease. The two patients had sectorial (temporal and inferior) optic atrophy based on the RNFL thinning detected by OCT. OCT‐A scans showed a decrease of the vascular network in the ONH and in the RPC layers corresponding to the sector of RNFL thinning.ConclusionsPeripapillary and optic nerve head temporal and inferior microvascular network were reduced in Wolfram patients. These findings confirm the preferential involvement of the small axons of the papillomacular bundle in dominant optic atrophy.
Panton‐Valentine leukocidin enhances glial reaction and microglial apoptosis through retinal ganglion and amacrine cell binding
Authors: Liu X. , Gaucher D. , Prevost G. , Heitz P. , Roux M.J. , Keller D. , Sauer A. 
Published: September 2017

PurposePanton‐Valentine leukocidin (PVL) may be a critical virulence factor of S. aureus during endophthalmitis. This study aimed to identify the retinal cell targets for PVL, and to analyze early retinal changes during infectionMethodsAfter intravitreous PVL injection, adult rabbits were put down at different time points (30 min, 1, 2 and 4 h). PVL location in retina, its binding receptor C5aR, changes of Müller cells and microglial cells were analyzed using immunohistochemistry in the vertical sections or whole mounted retinas.ResultsIn rabbit retina, only ganglion cells clearly were shown to express C5aR. PVL increasingly bound retinal ganglion cells (RGCs) with time, reaching 98% of labeled cells after 2 h of PVL presence. Displaced amacrine cells (DACs) did not express C5aR, but transiently bound PVL from 68% to 5% between 30 min to 4 h. Müller cells abnormally expressed Glial Fibrillary Acid Protein in external retina compared with controls. Microglial cells body and dendrites were enlarged and dendritic processes sensibly decreased at 2 h and even disappeared at 4h. At 4 h following PVL injection, both immunohistochemistry and Western blot showed that some microglial cells underwent apoptosis and nitrotyrosine accumulated in retina.ConclusionsIn this model of PVL eye infection, PVL rapidly binds two kinds of retinal neural cells: RGCs possibly through C5aR interaction, DACs through an unknown mechanism. Müller cells and microglial cells were activated very early during the PVL binding process, suggesting an inflammatory cross‐talk between retinal neural cells and glial cells. Some microglial cells underwent apoptosis after 4 h PVL infection, at least associated to an abnormal production of nitrotyrosine in the retina.
Effect of Dietary Antarctic Krill Meal on Growth Performance, Muscle Proximate Composition, and Antioxidative Capacity of Juvenile Spotted Halibut, Verasper variegatus
Authors: Yan Junli , Chang Qing , Chen Siqing , Wang Zhenjie , Lu Bin , Liu Changlin , Hu Jiangcheng 
Published: September 2017

AbstractA 7‐wk feeding trial was conducted to evaluate the effects of dietary Antarctic krill meal (AKM) on the growth performance, proximate composition of muscles, and antioxidative capacity of juvenile spotted halibut. Six diets were formulated to contain about 50% protein and 8% lipid. A control diet (R0) without AKM and the other five diets with 8.1, 16.2, 24.3, 32.4, and 42.5% AKM supplementation (R10–50) to replace 10, 20, 30, 40, and 50% fishmeal protein were used to feed to juvenile spotted halibut. The juveniles were fed with each diet using three replicates and cultivated in the indoor culture system. Results showed that the specific growth rate, feed intake, and protein efficiency ratio in the R30 and R40 groups were significantly higher than that in other groups (P < 0.05). Survival rate in the R50 group was significantly lower compared with the R0 group and the other four AKM supplementation groups. Moreover, the rising AKM levels in diets had significant effects on the chemical composition of juvenile spotted halibut, showing significantly decreased contents of crude protein, but increased lipid and ash contents (P < 0.05). The total superoxide dismutase activity and catalase activity of serum and liver in AKM groups were significantly higher than those in the control group (P < 0.05). In contrast, the contents of malondialdehyde in serum and liver were significantly lower compared with the control group. These findings illustrate that a moderate AKM level in diets can significantly improve the growth performance, feed utilization, and antioxidative capacity in juvenile spotted halibut, which support the finding that AKM may be used as a good protein source for halibut in the aquafeed industry.
Leukocyte and plasma activation profiles in chronically transfused patients with a history of allergic reactions
Authors: Fontaine Magali J. , Shih Hank , Schubert Richard , Wong Wendy , Andrews Jennifer , Jeng Michael , Tirouvanziam Rabindra 
Published: September 2017

BACKGROUNDAllergic transfusion reactions are drawbacks to the benefits of transfusion. Classically, allergic transfusion reactions depend on histamine release from mast cells or basophils, but other leukocyte subsets may also be important. Thus, we propose to better define the exact leukocyte subsets involved in allergic transfusion reactions.STUDY DESIGN AND METHODSThe overall objective of the current study was to compare the activation of specific peripheral blood leukocyte subsets (monocytes, neutrophils, eosinophils, and basophils) in a cohort of 13 patients who received chronic transfusions and had a history of allergic transfusion reactions compared with a control group of patients who received chronic transfusions and had no history of allergic transfusion reactions. Leukocyte subsets were analyzed by flow cytometry at baseline and after red blood cell transfusion, and cytokine levels in platelet‐free plasma collected at the same time points were measured by Luminex assay.RESULTSFlow cytometry and cytokine profiles before and after transfusion did not differ significantly between patients who did and did not have a history of allergic transfusion reactions (p > 0.05). However, post‐transfusion samples from both groups showed a decrease in CD63 expression in basophils, monocytes, and eosinophils and a decrease in CD45 expression in all leukocyte subsets compared with pretransfusion samples. Interleukin 10 levels increased after transfusion in the group with a history of allergic transfusion reactions (p = 0.0469), and RANTES (regulated upon activation, normal T‐cell expressed and secreted) was significantly decreased post‐transfusion in all patients (p = 0.0122).CONCLUSIONNone of the leukocyte subsets from patients who had a history of allergic transfusion reactions significantly increased in activation either before or after transfusion. All leukocyte subsets from patients who did and did not have a history of allergic transfusion reactions decreased in their activation profile upon transfusion challenge.
Multisite Evaluation of the BD Max Extended Enteric Bacterial Panel for Detection of Yersinia enterocolitica, Enterotoxigenic Escherichia coli, Vibrio, and Plesiomonas shigelloides from Stool Specimens
Authors: Simner Patricia J. , Oethinger Margret , Stellrecht Kathleen A. , Pillai Dylan R. , Yogev Ram , Leblond Helene , Mortensen Joel 
Published: September 2017

ABSTRACT

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of
Yersinia enterocolitica
, enterotoxigenic
Escherichia coli
(ETEC),
Vibrio
, and
Plesiomonas shigelloides
. The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was also used to confirm the historical results for the retrospective specimens and for discrepant result analysis. A total of 2,410 unformed, deidentified stool specimens were collected. The prevalence in the prospective samples as defined by the reference method was 1.2% ETEC, 0.1%
Vibrio
, 0%
Y. enterocolitica
, and 0%
P. shigelloides
. Compared to the reference method, the positive percent agreement (PPA) (95% confidence interval [CI]), negative percent agreement (NPA) (95% CI), and kappa coefficient (95% CI) for the BD Max xEBP assay for all specimens combined were as follows: ETEC, 97.6% (87.4 to 99.6), 99.8% (99.5 to 99.9), and 0.93 (0.87 to 0.99);
Vibrio
, 100% (96.4 to 100), 99.7% (99.4 to 99.8), and 0.96 (0.93 to 0.99);
Y. enterocolitica
, 99.0% (94.8 to 99.8), 99.9% (99.8 to 99.9), and 0.99 (0.98 to 1);
P. shigelloides
, 100% (96.4 to 100), 99.8% (99.5 to 99.9), and 0.98 (0.95 to 1), respectively. In this multicenter study, the BD Max xEBP showed a high correlation (kappa, 0.97; 95% CI, 0.95 to 0.98) with the conventional methods for the detection of ETEC,
Vibrio
,
Y. enterocolitica
, and
P. shigelloides
in stool specimens from patients suspected of acute gastroenteritis, enteritis, or colitis.
Mycoplasma genitalium Macrolide and Fluoroquinolone Resistance Detection and Clinical Implications in a Selected Cohort in New Zealand
Authors: Anderson Trevor , Coughlan Edward , Werno Anja 
Published: September 2017

ABSTRACT

Mycoplasma genitalium
has been associated with infections of the genitourinary tract, and prevalence is secondary to
Chlamydia trachomatis
. The clinical observation of increasing treatment failure indicating antibiotic resistance, especially in cases of recurrent urethritis, has been confirmed by molecular testing. Mutations in the 23S rRNA gene can cause macrolide resistance, and topoisomerase/gyrase mutations can cause fluoroquinolone resistance. In this study, 115
M. genitalium
DNA-positive samples were analyzed. Eighty-nine (77.4%) samples had a 23S rRNA mutation present, and 26 (22.6%) were wild type (no resistance mutation). Fluoroquinolone mutation screening was performed on 86 (74.8%) of the 115 samples, of which 20 (23.3%) samples had a mutation or mutations associated with increased resistance. This study shows the increasing antibiotic resistance in New Zealand and the need for appropriate guidelines to treat at-risk patients.
Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development
Authors: Puckette Michael , Clark Benjamin A. , Smith Justin D. , Turecek Traci , Martel Erica , Gabbert Lindsay , Pisano Melia , Hurtle William , Pacheco Juan M. , Barrera José , Neilan John G. , Rasmussen Max 
Published: September 2017

ABSTRACT

The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a
Gaussia
luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria.

IMPORTANCE
The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production.
Effect of Polymorphisms at Codon 146 of the Goat PRNP Gene on Susceptibility to Challenge with Classical Scrapie by Different Routes
Authors: Papasavva-Stylianou Penelope , Simmons Marion Mathieson , Ortiz-Pelaez Angel , Windl Otto , Spiropoulos John , Georgiadou Soteria 
Published: September 2017

ABSTRACT

This report presents the results of experimental challenges of goats with scrapie by both the intracerebral (i.c.) and oral routes, exploring the effects of polymorphisms at codon 146 of the goat
PRNP
gene on resistance to disease. The results of these studies illustrate that while goats of all genotypes can be infected by i.c. challenge, the survival distribution of the animals homozygous for asparagine at codon 146 was significantly shorter than those of animals of all other genotypes (chi-square value, 10.8;
P
= 0.001). In contrast, only those animals homozygous for asparagine at codon 146 (NN animals) succumbed to oral challenge. The results also indicate that any cases of infection in non-NN animals can be detected by the current confirmatory test (immunohistochemistry), although successful detection with the rapid enzyme-linked immunosorbent assay (ELISA) was more variable and dependent on the polymorphism. Together with data from previous studies of goats exposed to infection in the field, these data support the previously reported observations that polymorphisms at this codon have a profound effect on susceptibility to disease. It is concluded that only animals homozygous for asparagine at codon 146 succumb to scrapie under natural conditions.

IMPORTANCE
In goats, like in sheep, there are PRNP polymorphisms that are associated with susceptibility or resistance to scrapie. However, in contrast to the polymorphisms in sheep, they are more numerous in goats and may be restricted to certain breeds or geographical regions. Therefore, eradication programs must be specifically designed depending on the identification of suitable polymorphisms. An initial analysis of surveillance data suggested that such a polymorphism in Cypriot goats may lie in codon 146. In this study, we demonstrate experimentally that NN animals are highly susceptible after i.c. inoculation. The presence of a D or S residue prolonged incubation periods significantly, and prions were detected in peripheral tissues only in NN animals. In oral challenges, prions were detected only in NN animals, and the presence of a D or S residue at this position conferred resistance to the disease. This study provides an experimental transmission model for assessing the genetic susceptibility of goats to scrapie.
Lysine 242 within Helix 10 of the Pseudorabies Virus Nuclear Egress Complex pUL31 Component Is Critical for Primary Envelopment of Nucleocapsids
Authors: Rönfeldt Sebastian , Klupp Barbara G. , Franzke Kati , Mettenleiter Thomas C. 
Published: September 2017

ABSTRACT
Newly assembled herpesvirus nucleocapsids are translocated from the nucleus to the cytosol by a vesicle-mediated process engaging the nuclear membranes. This transport is governed by the conserved nuclear egress complex (NEC), consisting of the alphaherpesviral pUL34 and pUL31 homologs. The NEC is not only required for efficient nuclear egress but also sufficient for vesicle formation from the inner nuclear membrane (INM), as well as from synthetic lipid bilayers. The recently solved crystal structures for the NECs from different herpesviruses revealed molecular details of this membrane deformation and scission machinery uncovering the interfaces involved in complex and coat formation. However, the interaction domain with the nucleocapsid remained undefined. Since the NEC assembles a curved hexagonal coat on the nucleoplasmic side of the INM consisting of tightly interwoven pUL31/pUL34 heterodimers arranged in hexamers, only the membrane-distal end of the NEC formed by pUL31 residues appears to be accessible for interaction with the nucleocapsid cargo. To identify the amino acids involved in capsid incorporation, we mutated the corresponding regions in the alphaherpesvirus pseudorabies virus (PrV). Site-specifically mutated pUL31 homologs were tested for localization, interaction with pUL34, and complementation of PrV-ΔUL31. We identified a conserved lysine residue at amino acid position 242 in PrV pUL31 located in the alpha-helical domain H10 exposed on the membrane-distal end of the NEC as a key residue for nucleocapsid incorporation into the nascent primary particle.

IMPORTANCE
Vesicular transport through the nuclear envelope is a focus of research but is still not well understood. Herpesviruses pioneered this mechanism for translocation of the newly assembled nucleocapsid from the nucleus into the cytosol via vesicles derived from the inner nuclear membrane which fuse in a well-tuned process with the outer nuclear membrane to release their content. The structure of the viral nuclear membrane budding and scission machinery has been solved recently, providing in-depth molecular details. However, how cargo is incorporated remained unclear. We identified a conserved lysine residue in the membrane-distal portion of the nuclear egress complex required for capsid uptake into inner nuclear membrane-derived vesicles.