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

In vitro and in vivo degradation evaluation of Mg-based alloys for biomedical applications

2014-2015 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells

published_or_final_versio

Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow

Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P.) species with the P.falciparum being the most deadly. The parasites are capable of invading red blood cells (RBCs) during infection. At the late stage of parasites’ development, the parasites export proteins to the infected RBCs (iRBC) membrane and bind to receptors of surface proteins on the endothelial cells that line microvasculature walls. Resulting adhesion of iRBCs to microvasculature is one of the main sources of most complications during malaria infection. Therefore, it is important to develop a versatile and simple experimental method to quantitatively investigate iRBCs cytoadhesion and binding kinetics. Here, we developed an advanced flow based adhesion assay to demonstrate that iRBC’s adhesion to endothelial CD36 receptor protein coated channels is a bistable process possessing a hysteresis loop. This finding confirms a recently developed model of cell adhesion which we used to fit our experimental data. We measured the contact area of iRBC under shear flow at different stages of infection using Total Internal Reflection Fluorescence (TIRF), and also adhesion receptor and ligand binding kinetics using Atomic Force Microscopy (AFM). With these parameters, we reproduced in our model the experimentally observed changes in adhesion properties of iRBCs accompanying parasite maturation and investigated the main mechanisms responsible for these changes, which are the contact area during the shear flow as well as the rupture area size.Global Enterprise for Micro-Mechanics and Molecular MedicineUnited States. Dept. of Defense (DOD-ARO (W 911 NF-09-0480))Singapore–MIT Alliance for Research and Technology ((SMART) Fellowship)National Science Foundation (U.S.) (NSF Grant No.1112825

ZnO-based film bulk acoustic resonator for high sensitivity biosensor applications

Author name used in this publication: G. K. H. Pang2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

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

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males