Early Bilateral Amniotic Membrane Transplantation in the Management of Severe Ocular Involvement from Acute Toxic Epidermal Necrolysis in a Chinese Pediatric Patient

Introduction: Toxic Epidermal Necrolysis (TEN) is a rare but potentially life-threatening muco-cutaneous condition associated with idiosyncratic hypersensitivity to certain drugs. Ophthalmic involvement is common, typically affecting the ocular surface and eyelids. Survivors often suffer from resulting bilateral blindness and ocular dryness or pain. Objective: To report the successful management of severe ocular surface disease during the acute stage of toxic epidermal necrolysis using early amniotic membrane transplantation on both eyes in a Chinese paediatric patient. Design: Interventional case report Case Report: A 15 year-old Chinese girl was transferred to the intensive care unit of Queen Mary Hospital, Hong Kong with TEN after taking oral cefuroxime and diclofenac. She developed bilateral keratoconjunctivitis, diffuse corneal epithelial defects (80-90% of cornea surface) and later bilateral symblephara. After initial treatment with daily rodding, topical lubricants, steroids and antibiotics, there was no improvement in her condition. Bilateral amniotic membrane transplantation (AMT) was performed over the cornea, fornix, tarsal and bulbar conjunctiva on day 10 of illness. On discharge from the hospital (post-operative week 7), the patient had pinhole visual acuity of 6/7.5 in the right eye and 6/6 the left eye. She was eventually weaned off all topical medication. Visual acuity eventually recovered to 6/6 in both eyes by week 20 after surgery. There was mild residual forniceal symblepharon and eyelid margin keratinization. She continues to require regular lubricants for her chronic ocular surface condition.published_or_final_versio

Ambulatory intraocular pressure fluctuation recording with a novel wireless smart silicone contact lens sensor

The Conference program's website is located at http://apacrs2014.org/free_papers.htmlSession - FP1: General: no. FP1-03INTRODUCTION: Monitoring of treatment response in the management of glaucomatous optic neuropathy relies on single intraocular pressure (IOP) measurements during regular clinic hours at regular intervals. However IOP is a dynamic parameter with circadian rhythms as well as posture and exercise related fluctuations. The introduction of continuous 24 hour IOP monitoring technology has created a paradigm shift in glaucoma management. Our wireless smart contact lens sensor was previously validated in-vivo and ex-vivo in animal models. Here we describe the performance of the sensor in ...postprin

Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio

Effects of Magnetic Field Orientations in Dense Cores on Gas Kinematics in Protostellar Envelopes

Theoretically, misalignment between the magnetic field and rotational axis in a dense core is considered to be dynamically important in the star formation process; however, the extent of this influence remains observationally unclear. For a sample of 32 Class 0 and I protostars in the Perseus Molecular Cloud, we analyzed gas motions using C18O data from the SMA MASSES survey and the magnetic field structures using 850 μm polarimetric data from the JCMT BISTRO-1 survey and archive. We do not find any significant correlation between the velocity gradients in the C^{18}O emission in the protostellar envelopes at a 1000 au scale and the misalignment between the outflows and magnetic field orientations in the dense cores at a 4000 au scale, and there is also no correlation between the velocity gradients and the angular dispersions of the magnetic fields. However, a significant dependence on the misalignment angles emerges after we normalize the rotational motion by the infalling motion, where the ratios increase from ≲1 to ≳1 with increasing misalignment angle. This suggests that the misalignment could prompt angular momentum transportation to the envelope scale but is not a dominant factor in determining the envelope rotation, and other parameters, such as mass accretion in protostellar sources, also play an important role. These results remain valid after taking into account projection effects. The comparison between our estimated angular momentum in the protostellar envelopes and the sizes of the known protostellar disks suggests that significant angular momentum is likely lost between radii of ∼1000 and 100 au in protostellar envelopes

Phosphorylation of LCRMP-1 by GSK3β Promotes Filopoda Formation, Migration and Invasion Abilities in Lung Cancer Cells

LCRMP-1, a novel isoform of CRMP-1, can promote cancer cell migration, invasion and associate with poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). However, the underlying regulatory mechanisms of LCRMP-1 in cancer cell invasiveness still remain obscure. Here, we report that GSK3β can phosphorylate LCRMP-1 at Thr-628 in consensus sequences and this phosphorylation is crucial for function of LCRMP-1 to promote filopodia formation, migration and invasion in cancer cells. Impediment of Thr-628 phosphorylation attenuates the stimulatory effects of LCRMP-1 on filopodia forming, migration and invasion abilities in cancer cells; simultaneously, kinase-dead GSK3β diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3β expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3β expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3β-dependent phosphorylation of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer cell invasiveness and clinical outcome

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Modulates Reversible Cerebral Vasoconstriction Syndromes

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) could be complicated by cerebral ischemic events. Hypothetical mechanisms of RCVS involve endothelial dysfunction and sympathetic overactivity, both of which were reported to be related to brain-derived neurotrophic factor (BDNF). The study investigated the association between functional BDNF Val66Met polymorphism and RCVS. METHODS: Patients with RCVS and controls were prospectively recruited and genotyped for the BDNF Val66Met polymorphism. Magnetic resonance angiography (MRA) and transcranial color-coded Doppler sonography were employed to evaluate cerebral vasoconstriction. Genotyping results, clinical parameters, vasoconstriction scores, mean flow velocities of the middle cerebral artery (V(MCA)), and Lindegaard indices were analyzed. Split-sample approach was employed to internally validate the data. PRINCIPAL FINDINGS: Ninety Taiwanese patients with RCVS and 180 age- and gender-matched normal controls of the same ethnicity completed the study. The genotype frequencies did not differ between patients and controls. Compared to patients with Met/Met homozygosity, patients with Val allele had higher mean vasoconstriction scores of all arterial segments (1.60±0.72 vs. 0.87±0.39, p<0.001), V(MCA) values (116.7±36.2 vs. 82.7±17.9 cm/s, p<0.001), and LI (2.41±0.91 vs. 1.89±0.41, p = 0.001). None of the Met/Met homozygotes, but 38.9% of the Val carriers, had V(MCA) values of >120 cm/s (p<0.001). Split-sample validation by randomization, age, entry time or residence of patients demonstrated concordant findings. CONCLUSIONS: Our findings link BDNF Val66Met polymorphism with the severity of RCVS for the first time and implicate possible pathogenic mechanisms for vasoconstriction in RCVS

Identification of a novel splice variant form of the influenza a virus m2 ion channel with an antigenically distinct ectodomain

Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42) with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle

The JCMT BISTRO Survey: multiwavelength polarimetry of bright regions in NGC 2071 in the far-infrared/submillimetre range, with POL-2 and HAWC+

Polarized dust emission is a key tracer in the study of interstellar medium and of star formation. The observed polarization, however, is a product of magnetic field structure, dust grain properties, and grain alignment efficiency, as well as their variations in the line of sight, making it difficult to interpret polarization unambiguously. The comparison of polarimetry at multiple wavelengths is a possible way of mitigating this problem. We use data from HAWC+ /SOFIA and from SCUBA-2/POL-2 (from the BISTRO survey) to analyse the NGC 2071 molecular cloud at 154, 214, and 850 μm. The polarization angle changes significantly with wavelength over part of NGC 2071, suggesting a change in magnetic field morphology on the line of sight as each wavelength best traces different dust populations. Other possible explanations are the existence of more than one polarization mechanism in the cloud or scattering from very large grains. The observed change of polarization fraction with wavelength, and the 214-to-154 μm polarization ratio in particular, are difficult to reproduce with current dust models under the assumption of uniform alignment efficiency. We also show that the standard procedure of using monochromatic intensity as a proxy for column density may produce spurious results at HAWC+wavelengths. Using both long-wavelength (POL-2, 850 μm) and short-wavelength (HAWC+, ≲200μm) polarimetry is key in obtaining these results. This study clearly shows the importance of multi-wavelength polarimetry at submillimetre bands to understand the dust properties of molecular clouds and the relationship between magnetic field and star formation

Convergent Evidence from Mouse and Human Studies Suggests the Involvement of Zinc Finger Protein 326 Gene in Antidepressant Treatment Response

OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response