bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic Activity of CYP1B1 in primary congenital glaucoma goniodysgenesis and its relation with histological alterations
Authors: Ramirez A.I. , Garcia‐Anton M. , Salazar J.J. , de Hoz R. , Rojas B. , Garcia‐Feijoo J. , Triviño A. , Escribano J. , Ramirez J.M.
Published: September 2017

Purpose

To analyze de CYP1B1 genotype activity, the histological findings and the clinical phenotypes in human primary congenital glaucoma (PCG).

Methods

Transmission electron microscopy was used to study surgical pieces from trabeculectomy from PCG patients (n = 5) and normal cadaver donors sclerocorneal rims (n = 3). Genomic DNA was extracted from the peripheral leukocytes of the same patients for the CYP1B1 study.

Results

The histological analysis allowed us to classified patient samples into three groups depending on goniodysgenesis findings: A) no visualization of the Schlemm's canal (SC); B) presence of the SC and no visualization of the collector channels (CC); C) presence of the SC and CC. Patients from groups A and B had extensive trabecular endothelial cell necrosis, and abnormal trabecular beam and null enzymatic activity of CYP1B1. Patients from group C in addition to presence of the SC and CC, showed a more developed trabecular meshwork than groups A and B and trabecular endothelial cells alive and with signs of phagocytic. This group showed a 60% of enzymatic activity of CYP1B1. All groups shared an abnormal insertion of the ciliary muscle although in group C the insertion was in a more posterior position.

Conclusions

In the samples analyzed, it seems to have a relationship between enzymatic activity of CYP1B1 and histological changes. The lower the CYP1B1 gene enzymatic activity, the greater the goniodisgenesys and the trabecular endothelial cell death extent. A greater understanding of histological changes associated with the enzymatic activity of CYP1B1 could be useful for clinicians to plan treatment strategy. This data could be useful for clinicians to plan treatment strategy
Glaucoma assessment tools used by clinicians: old or gold?
Authors: Marques R.E. , Sousa D.C. , Leal I. , Sens P. , Marques‐Neves C. , Pinto L.A.
Published: September 2017

Purpose

Glaucoma is the main cause of irreversible blindness worldwide. Early detection and personalized management is the key to prevent or slow disease progression. Our group previously evaluated the quality of within‐hospital referral to a glaucoma subspecialty department (GSD), raising awareness to the importance of doing applanation tonometry (AT), gonioscopy and visual fields (VF) before referral. The aim of this work was to perform an audit cycle, one year after the awareness training session in December 2015.

Methods

Retrospective analysis of a random sample of within‐hospital referrals to the GSD, in Lisbon Academic Medical Center (January 2016 to May 2017). Electronic records were screened for clinical data, exams, medical and surgical treatments prior to referral. Descriptive statistics were performed with SPSS.

Results

A total of 150 patients (69 males) were included in this analysis, with a mean age of 65 years [range 10–93]. Mean intraocular pressure (IOP) was 19.8 mmHg. Almost 20% of patients were not on any IOP‐lowering drugs, while nearly half were under ≥2 classes of treatment. AT and VF were performed respectively in 43% and 59% of the referred patients, both versus 49% in 2015 (p > 0.05). Gonioscopy was described for 23% of patients, more than the 12% mentioned in 2015 (p = 0.014). Optical coherence tomography (OCT) was performed in the large majority, 85%, as in the first analysis. Only 6% of patients had all AT, gonioscopy and VF; and 19% were referred with none of these exams, comparing to the 22% in the original 2015 screening (p > 0.05).

Conclusions

Overall, training session did not significantly improve the quality of GSD referral, though more physicians reported gonioscopy results. It seems many clinicians still prefer more expensive and sophisticated exams as OCT, often forgetting valuable and simpler tools.
Changes in the X‐ray diffraction pattern of porcine lens before and after simulated accommodation
Authors: Al‐Atawi S. , Albon J. , Meek K. , Hayes S. , Bell J. , Regini J.
Published: September 2017

Purpose

During the accommodation process, the morphology of the lens changes. The crystallin proteins within the lens fibres are the primary structural unit of organisation at the cellular level, and play a major role in maintaining transparency and refractive power. All the structural information about the lens from X‐ray scattering techniques have so far been performed on samples in the relaxed accommodated state. It is thought that largest structural changes occur in the lens nucleus during accommodation.

Aims

To measure any changes in the average distance between the crystallin proteins, and their ordering within the lens fibres before and after stretching using small angel x‐ray scattering.

Methods

Fresh porcine lenses were mounted into a commercially available lens stretching device (Bioniko, Florida, USA). Samples were placed in the X‐ray beam at the Diamond synchrotron and 2D grid scans performed. Scans were taken in the same lens in both the accommodated and unaccommodated states, before and after a stretching.

Results

All patterns show a reduction in both the X‐ray intensity and in the average spacing between the crystallin proteins, in the centre of the lens compared with the periphery. This is consistent with the increase of protein concentration from the lens cortex to the nucleus. No significant changes in the average spacing between the crystallin proteins was observed upon stretching. Substantial changes in both the X‐ray intensity, and in the ordering of the proteins were recorded at the peripheral margins of lenses in the stretched state.

Conclusions

The changes in the X‐ray intensity, and in the ordering of the crystallin proteins at the peripheral margins of the lens are somewhat in contrast to the notion that the nucleus under goes the largest structural changes.
Serum adiponectin associates with aging rather than neovascular AMD
Authors: Paterno J.J. , Kauppinen A. , Kaarniranta K.
Published: September 2017

Purpose

To study whether adiponectin serum levels are changed in neovascular AMD. Adiponectin, secreted primarily by adipocytes, modulates cellular energy metabolism. Adiponectin participates also in retinal homeostasis and autophagy. Adiponectin receptors are abundant in RPE‐choroid level. We have previously reported that ADIPOR1‐gene variant associates with advanced AMD in Finnish population. Here, we evaluate the role of peripheral adiponectin in AMD.

Methods

After obtaining written informed consent, venous blood samples were collected from 145 neovascular AMD patients (mean age: 79.4 ± 6.1 years) and 90 controls (mean age: 74.6 ± 6.3 years) in a cross‐sectional design. Other causes of macular oedema were excluded. Serum adiponectin levels were quantified using a commercial ELISA kit.

Results

Serum levels of adiponectin in neovascular AMD group (12.0 ± 9.5 μg/mL) did not significantly differ from levels in control group (11.1 ± 7.8 μg/mL; t‐test p = 0.423). Adiponectin levels increased with aging (rs = 0.237, p = 0.01). Women had higher mean adiponectin levels (13.2 ± 9.4 μg/mL, n = 175) compared to men (7.8 ± 6.2 μg/mL, n = 70; t‐test p = 0.001), but no difference was detected between AMD‐patients and controls when analyzed separately by gender (women: 13.2 ± 8.6 μg/mL vs. 13.2 ± 9.9 μg/mL, respectively; t‐test p = 0.959; men: 8.3 ± 7.5 μg/mL vs. 7.2 ± 4.0 μg/mL, respectively; t‐test p = 0.439).

Conclusions

Our findings suggest that serum adiponectin levels are not altered in neovascular AMD. However, adiponectin may be considered more like a general serum biomarker of aging. As already known, gender can influence the adiponectin level in elderly.
The investigation of the distribution of nerves, blood vessels and immune cells on the fresh human corneal surface using optimized protocols for immunostaining of flat mounted whole cornea
Authors: He Z. , Guindolet D. , Forest F. , Cognasse F. , Acquart S. , Perrache C. , Gabison E. , Bergandi F. , Gain P. , Thuret G.
Published: September 2017

Purpose

To present a reliable protocol for the immunostaining of flat mounted corneas and provide a map of the distribution of nerves, blood vessels and immune cells on fresh human corneal epithelium and conjunctiva.

Methods

Organ‐cultured human corneas were used for our technique development. 15 fixatives and 5 antigen retrieval (AR) methods were assessed using 4 ubiquitous proteins with different, well‐characterized subcellular localization: ZO‐1 (membrane), actin (cytoplasm), hnRNP L (nucleosol) and histone H3 (chromatin). The distribution of nerves (Neurofilaments and tubulin β3), blood vessels (CD31 and α‐SMA) and immune cells (CD45, CD4, CD8, CD68) in fresh human corneas (without any preservation in culture medium) was then investigated using these optimized protocols.

Results

0.5% paraformaldehyde (PFA) and pure methanol were selected as the most efficient fixatives. Using our optimised protocol, we revealed not only superficial cells (cytokeratin 3, E‐cadherin), but also basal cells (ΔNp63, PAX6). Nerve fibers were mainly stained by tubulin β3 on epithelium and by Neurofilament on conjunctiva. CD31 stained only the capillaries situated at the limbus, whereas α‐SMA stained all types of vessels on the corneal surface. Numerous immune cells were detected on conjunctival and capillary loops below the limbus. A few immune cells were observed on central epithelium.

Conclusions

Tissue fixation with 0.5% PFA or pure methanol, without any subsequent AR techniques, were found to produce the best results. Compared to IHC on cross sections, immunostaining of flat mounted cornea allows a precise localization of targeted cells through the full thickness of the corneal epithelium and conjunctiva. The distribution of nerves, blood vessels and immune cells on the corneal surface has therefore been mapped.
A holistic dynamic concept on the pathophysiology in dry eye disease
Authors: Knop E. , Knop N.
Published: September 2017

Absrtact

Purpose

Dry Eye Disease (DED) is still insufficiently understood because it is a complex alteration of the functional anatomy of the ocular surface. Current concepts are often oversimplified and a new realistic model is developed that reflects all relevant aspects.

Methods

. A NLM PubMed based review of the literature on DED was performed. Pathogenetic mechanisms were identified and arranged in a patho‐physiologic hierarchy of causative relations that reflects clinical findings but is independent of assumed ′importance′.

Results

Basic primary causative factors for DED are structural and functional alterations of the ocular surface integrity. This concerns a deficiency of (A) tear component SECRETION by the secretory elements and of (B) tear FILM FORMATION by the eye lids and blinking mechanism. Together this leads to the two main pathologies of (1) TEAR FILM DEFICIENCY and thus insufficient permanent wetting of the interpalpebral surface that causes (2) the well‐known SURFACE TISSUE DAMAGE that gives rise to signs and symptoms. Both pathologies are governed by several interacting secondary pathogenetic factors. Typical for the complex disease mechanism are self‐enforcing vicious circles ‐ in contrast to present over‐simplified models they do not necessarily depend on inflammation and there are in fact several, different, interacting vicious circles instead of just one. The disease process is influenced by an impairment of regulatory systems (innervation, endocrine system, immune system) of the body & by negative internal and external risk factors.

Conclusions

This new holistic dynamic concept on the pathophysiology DED incorporates long established as well as new mechanisms in the pathophysiological order. It is complex but not complicated ‐ intuitively understandable and suitable to assist basic scientist, patients, and clinical practitioner alike.
Macrogilal retinal cells show a bilateral early activation in a mouse model of unilateral laser‐induced experimental glaucoma
Authors: Salazar J.J. , de Hoz R. , Ramirez A.I. , Salobrar‐Garcia E. , Rojas B. , VidalSanz M. , Triviño A. , Ramirez J.M.
Published: September 2017

Purpose

To describe macroglial morphological features of activation after 24 h of unilateral laser‐induced ocular hypertension (OHT) in OHT‐eyes and their contralateral eyes.

Methods

Albino Swiss mice were divided into two groups, naïve (n = 6) and lasered (n = 6). Retinal whole‐mounts were immunolabeled with antibodies against GFAP and MHC‐II.

Results

With respect to naïve, OHT eyes and contralateral eyes showed different features of macroglial activation in some retinal areas: i) Müller cells were reactive and expressed GFAP; ii) astrocytes were more robust and had more primary and secondary processes; and iii) MHCII was up‐regulated in astrocytes and in some Müller cells. In contralateral eyes, these signs were observed mainly in the periphery. In addition, in the OHT eyes: i) in some retinal vessels near the optic disc, the astroglial reactivity was so intense that the entire vascular walls were sheathed by astroglial cells; ii) in some areas of the retina, astrocytes and Müller cells formed glial scars. iii) MHC‐II immunoreaction in astrocytes varied depending on the retinal area; in those in which MHC‐II immunostaining was less intense, only astrocyte primary processes could be recognized;

Conclusions

At 24 h after unilateral OHT, macroglia showed features of activation not only in OHT eyes, but also in untreated contralateral eyes. Early up‐regulation of MHC‐II in macroglial cells in both OHT retinas and contralateral retinas, suggest an immune system‐related inflammation early after the induction of ocular hypertension.
Choroidal thickness measurements around the optic disc in healthy subjects using Swept‐Source optical coherence device
Authors:  Ciprés Alastuey M. ,  García Martín E. ,  Bambó Rubio M.P. ,  Vilades Palomar E. ,  Rodrigo Sanjuan M.J. ,  Satué Palacián M. ,  Orduna Hospital E. ,  Obis Alfaro J.
Published: September 2017

Purpose

To measure the peripapillary choroidal thickness in an extensive area around the optic nerve and several established sections in healthy subjects using a swept‐source optical coherence tomography (SS‐OCT) device.

Methods

A total of 86 healthy subjects were included in the study. An optic disc 6.0 × 6.0 mm three‐dimensional scan of the right eye was obtained using the Deep Range Imaging (DRI) OCT Triton. Centered in the optic disc a 26x26 cube‐grid was generated to automatically measure the choroidal thickness. Seven choroidal zones were established and analysed: 3 superior (temporal, central, and nasal), 3 inferior (temporal, central, and nasal) and the optic nerve head

Results

Peripapillary coroidal thickness was significantly thinner in the central superior, nasal superior, and nasal inferior zones in healthy eyes. Choroidal thickness in the central superior zone was 156.17 ± 80.89 μm; in the nasal superior zone was 168.34 ± 73.45 μm and in the nasal inferior zone was 137.47 ± 65.96 μm.

Conclusions

Peripapillary choroidal thickness in healthy subjects is higher in the temporal and superior zones around the optic disc. SS‐OCT could be a useful tool to evaluate choroidal thinning.
Cabin pressure aboard commercial aircraft and non‐arteritic ischemic optic neuropathy
Authors: Nazarali S. , Liu H. , Syed M. , Ter‐Zakarian A. , Karanjia R. , Sadun A.A.
Published: September 2017

Purpose

To evaluate variations in pressurization of commercial aircraft at cruising altitude. Most aircraft are pressurized between 6,000 and 8,000 feet (ft.), depending on the type of aircraft and composite materials of the fuselage. Patients with NAION may note transient obscurations of vision in concert with low partial pressures of oxygen associated with high altitude.

Methods

Altimeters were used to measure the altitude and cabin pressure at cruising altitude aboard 83 commercial aircraft, including 38 narrow‐body and 45 wide‐body planes. Single‐aisle aircraft with a fuselage width of 10‐13 ft. were considered narrow‐body, while twin‐aisle aircraft with a fuselage width of 16‐20 ft. were qualified as wide‐body. There were six types of narrow‐body and seven types of wide‐body aircraft studied.

Results

The mean cabin pressure among all flights was 6,200 ± 970 ft. Narrow‐body aircraft had a significantly greater mean cabin pressure of 6,634 ± 965 ft. compared to wide‐body aircraft with a mean cabin pressure of 5,834 ± 818 ft. (p < 0.001). With respect to service date, newer generation aircraft had a mean cabin pressure of 5,999 ± 949 ft., which was lower than the mean cabin pressure of older aircraft 6,462 ± 946 ft. (p = 0.03).

Conclusions

Innovation in flight design has offered the ability for aircraft to fly at greater altitudes, while maintaining lower cabin pressures. Those at high risk of hypoxia induced complications such as NAION may consider aircraft type when air travel is required. Although all flights studied maintained pressurization below suggested United States Federal Aviation Administration (FAA) guidelines, the possibility for oxygen desaturation remains with current flight practices, especially in those at high risk.
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

Purpose

Leber'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.

Methods

Age 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.

Results

Clinical 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.

Conclusions

The 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

Purpose

LHON 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.

Methods

The 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).

Results

Of 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.

Conclusions

LHON 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

Purpose

To 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).

Methods

This 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.

Results

The 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.

Conclusions

Peripapillary 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

Purpose

Panton‐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 infection

Methods

After 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.

Results

In 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.

Conclusions

In 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

A 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

BACKGROUND

Allergic 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 METHODS

The 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.

RESULTS

Flow 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).

CONCLUSION

None 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.
Block copolymer directed self-assembly using chemoepitaxial guiding underlayers with topography
Authors: Nation Benjamin D. , Ludovice Peter J. , Henderson Clifford L.
Published: September 2017

Guiding underlayers are used in the directed self-assembly of block copolymers (BCPs) to form large defect free arrays. These underlayers traditionally have divided into two categories: chemoepitaxial underlayers which guide the BCP using regions of differing chemical preference and graphoepitaxial guiding underlayers which guide by topographic features built into the underlayer. However, multiple hybrid approaches have been introduced over recent years using both topographic features and chemical preference to direct the BCP film. In this work, a coarse-grained molecular dynamics model is used to explore both the geometric aspects and the chemical preferences of these hybrid underlayers and the effect these variables have on the defectivity of the BCP film. It is found that hybrid underlayers with vertical sidewalls behave in manners similar to more purely graphoepitaxial guiding underlayers, while hybrid underlayers with sloped sidewalls behave in a manner similar to chemoepitaxial guiding underlayers. With vertical sidewalls, it is found that larger topographic step heights decrease defectivity although with diminishing returns. It is found that the width of the trench in these cases should be an integer multiple of the natural repeat distance of the block copolymer although the width of the trench can have approximately 10% error before significantly affecting the defectivity of the simulated BCP. With straight sidewalls, the ideal case is to have a neutral surface on top of the mesa and at the bottom of the trench. A variety of sloped sidewalls were explored. It was found that with sloped sidewalls, there is an optimal topographic height that minimizes defectivity. It was also found that a triangular topographic feature yields far lower defectivity than a similarly sized rectangular topographic feature.
Speech intelligibility is best predicted by intensity, not cochlea-scaled entropy
Authors: Oxenham Andrew J. , Boucher Jeffrey E. , Kreft Heather A.
Published: September 2017

Cochlea-scaled entropy (CSE) is a measure of spectro-temporal change that has been reported to predict the contribution of speech segments to overall intelligibility. This paper confirms that CSE is highly correlated with intensity, making it impossible to determine empirically whether it is CSE or simply intensity that determines speech importance. A more perceptually relevant version of CSE that uses dB-scaled differences, rather than differences in linear amplitude, failed to predict speech intelligibility. Overall, a parsimonious account of the available data is that the importance of speech segments to overall intelligibility is best predicted by their relative intensity, not by CSE.
Ghost reefs: Nautical charts document large spatial scale of coral reef loss over 240 years
Authors: McClenachan Loren , O’Connor Grace , Neal Benjamin P. , Pandolfi John M. , Jackson Jeremy B. C.
Published: September 2017

Nautical charts from the 18th century document loss of nearshore coral reef habitat, revealing a shifted spatial baseline.
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

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

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

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

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

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.
Caecal cancer presenting as leg erythema and a lung opacity
Authors: Das Archik , Hureibi Khalid , Tayyab Muhammad , McCullough Peter
Published: September 2017

Necrotising infection of the lower limb is a rare presentation for colorectal malignancy. We report a case of a perforated caecal adenocarcinoma presenting with right leg erythema, pain and swelling in the presence of a right lower lobe lung opacity. Following initial debridement and washout, CT imaging demonstrated a thickened terminal ileum, caecum and appendix, in keeping with primary malignancy. This fed the right-sided lower limb sepsis tracking down from the medial aspect of the psoas muscle to give rise to the multiloculated collection seen in the adductor compartment. The lung lesion measured 16 mm and was metastatic. The patient was successfully managed with a subtotal colectomy and an end ileostomy. The biopsy confirmed an adenocarcinoma (T4N1M1). We highlight the importance of perforated colonic carcinoma as a leading differential for lower limb abscesses. Suspicions should be raised further if accompanied by rounded opacifications on plain film radiography of the lungs.
Systematic review of the evidence on orthotic devices for the management of knee instability related to neuromuscular and central nervous system disorders
Authors: McDaid Catriona , Fayter Debra , Booth Alison , O'Connor Joanne , Rodriguez-Lopez Rocio , McCaughan Dorothy , Bowers Roy , Iglesias Cynthia P , Lalor Simon , O'Connor Rory J , Phillips Margaret , Ramdharry Gita
Published: September 2017

Objectives

To assess the effectiveness of orthotic devices for the management of instability of the knee in adults with a neuromuscular disorder or central nervous system disorder.

Design

A systematic review of primary studies.

Setting

Community.

Participants

Adults with a neuromuscular disorder or central nervous system disorder and impaired walking ability due to instability of the knee.

Interventions

Orthoses with the clinical aim of controlling knee instability, for example, knee-ankle-foot orthoses, ankle-foot orthoses and knee orthoses or mixed design with no restrictions in design or material.

Primary and secondary outcome measures

Condition-specific or generic patient-reported outcome measures assessing function, disability, independence, activities of daily living, quality of life or psychosocial outcomes; pain; walking ability; functional assessments; biomechanical analysis; adverse effects; usage; patient satisfaction and the acceptability of a device; and resource utilisation data.

Results

Twenty-one studies including 478 patients were included. Orthotic devices were evaluated in patients with postpolio syndrome, poststroke syndrome, inclusion body myositis and spinal cord injury. The review included 2 randomised controlled trials (RCTs), 3 non-randomised controlled studies and 16 case series. Most were small, single-centre studies with only 6 of 21 following patients for 1 year or longer. They met between one and five of nine quality criteria and reported methods and results poorly. They mainly assessed outcomes related to gait analysis and energy consumption with limited use of standardised, validated, patient-reported outcome measures. There was an absence of evidence on outcomes of direct importance to patients such as reduction in pain and falls.

Conclusions

There is a need for high-quality research, particularly RCTs, of orthotic devices for knee instability related to neuromuscular and central nervous system conditions. This research should address outcomes important to patients. There may also be value in developing a national registry.

Registration number systematic review

PROSPERO (CRD42014010180).