Retained Herrick Plug.

A 79-year-old female with a history of keratoconjunctivitis sicca presented with several years of epiphora of both eyes. Thirteen years earlier, intracanalicular Herrick lacrimal plugs (Lacrimedics, Eastsound, WA, USA) had been placed in both eyes to treat her dry eye syndrome. After 13 years the patient felt the epiphora was intolerable and underwent endoscopic dacryocystorhinostomy (DCR) of the left, then the right side. Intraoperatively, during the right endoscopic DCR, a Herrick lacrimal plug was found in the common canaliculus into the lacrimal sac. Postoperatively, the patient did well with improved epiphora. The Herrick plug is designed to be intracanalicular, and this case illustrates that the plug can migrate and be retained for many years. Collared punctal plugs have a lower risk of this type of complication

Pigmented basal cell carcinoma of the eyelid in Hispanics

Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC) of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesion

DEVELOPING AN ONLINE CORPUS OF FORMOSAN LANGUAGES

Information technologies have now matured to the point of enabling researchers to create a repository of language resources, especially for those languages facing the crisis of endangerment. The development of an online platform of corpora, made possible by recent advances in data storage, character-encoding and web technology, has profound consequences for the accessibility, quantity, quality and interoperability of linguistic field data. This is of particular significance for Formosan languages in Taiwan, many of which are on the verge of extinction. As a response to the recognition of this burgeoning problem, the key objectives of the establishment of the NTU Corpus of Formosan Languages aim to document and thus preserve valuable linguistic data, as well as relevant ethnological and cultural information. This paper will introduce some of the theoretical bases behind this initiative, as well as the procedures, transcription conventions, database normalization, in-house system and three special features in the creation of this corpus

Yeast Screen for Constitutively Active Mutant G Protein–Activated Potassium Channels

AbstractGIRK2 is a major contributor to G protein–activated inward rectifier potassium channels in the mammalian brain. How GIRK channels open upon contact with Gβγ remains unknown. Using a yeast genetic screen to select constitutively active mutants from a randomly mutagenized GIRK2 library, we identified five gating mutations at four residues in the transmembrane domain. Further mutagenesis indicates that GIRK channel opening involves a rotation of the transmembrane segments, bringing one of these residues (V188) to a pore-lining position in the open conformation. Combined with double-mutant studies, these findings suggest that GIRK channels gate by moving from the open conformation inferred from our yeast study of Kir2.1 to a closed conformation perhaps resembling the known KcsA structure

The prognostic factors for locally advanced cervical cancer patients treated by intensity-modulated radiation therapy with concurrent chemotherapy

Background/PurposeTo identify the prognostic factors for locally advanced cervical cancer patients treated by intensity-modulated radiotherapy (IMRT) and concurrent cisplatin-based chemotherapy.MethodsA total of 125 patients with stage IB2–III cervical carcinoma were treated with IMRT and concurrent cisplatin-based chemotherapy, plus high dose rate (HDR) brachytherapy between January 2004 and November 2010, in our institution. All patients received external irradiation of 45–54 Gy with the IMRT technique and concurrent cisplatin-based chemotherapy monthly or weekly. HDR brachytherapy of 20–30.5 Gy was prescribed to point A, as a local boost. Prognostic factors including age, histology, stage, lymph nodes metastasis, pretreatment hemoglobin level, serum squamous cell carcinoma antigen (serum SCC-Ag), chemotherapy regimens and the cumulative dose of weekly cisplatin, were analyzed. The endpoints were overall survival (OS), local failure-free survival (LFFS) and disease-free survival (DFS).ResultsThe median follow-up time was 42 months. The 4-year OS, LFFS and DFS were 73.8%, 77.9% and 67.2%, respectively. Four (3.2%) patients developed ≥grade 3 acute gastrointestinal (GI) toxicity and 29 (23.2%) patients developed ≥grade 3 acute hematological toxicity. Five (4.0%) patients developed ≥grade 3 late GI toxicity and seven (5.6%) patients developed ≥grade 3 late genitourinary system toxicity. On univariate analysis, adenocarcinoma was a poor prognostic factor for OS (p = 0.05), LFFS (p = 0.01) and DFS (p = 0.006). Patients with lymph nodes metastasis at diagnosis had worse OS (p = 0.02). The high cumulative dose of cisplatin (>180 mg/m2) had better OS (p = 0.03) and tended to have better survival on LFFS (p = 0.13) and DFS (p = 0.10). On multivariate analysis, adenocarcinoma was a significant independent prognostic factor for OS (p = 0.001), LFFS (p = 0.005) and DFS (p < 0.001). Initial lymph nodes metastasis was an independent predictor of OS (p = 0.013). Cumulative dose of weekly cisplatin significantly affected OS (p = 0.041), and high cumulative dose of cisplatin tended to have better LFFS (p = 0.083). Higher pretreatment hemoglobin level had better LFFS (p = 0.034).ConclusionAdenocarcinoma and lymph nodes metastases were poor prognostic factors for patients with locally advanced cervical cancer. Lower pretreatment hemoglobin level had poorer local control. Chemotherapy with a high cumulative dose of cisplatin tended to result in better survival

CRISPR-Mediated VHL Knockout Generates an Improved Model for Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma (mRCC) is nearly incurable and accounts for most of the mortality associated with RCC. Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority of clear cell RCC (ccRCC) cases. Its role in regulating hypoxia-inducible factors-1α (HIF-1α) and -2α (HIF-2α) is well-studied. Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transition (EMT) phenotype. In this study we showed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecular changes indicative of EMT, which in turn drives increased metastasis to the lungs. RENCA cells deficient in HIF-1α failed to undergo EMT changes upon VHL knockout. RNA-seq revealed several HIF-1α-regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an aggressive form of ccRCC in the cancer genome atlas (TCGA) database. Independent validation in a new clinical dataset confirms the upregulation of these genes in ccRCC samples compared to adjacent normal tissue. Our findings indicate that loss of VHL could be driving tumour cell dissemination through stabilization of HIF-1α in RCC. A better understanding of the mechanisms involved in this phenomenon can guide the search for more effective treatments to combat mRCC

Kirigami-inspired, highly stretchable micro-supercapacitor patches fabricated by laser conversion and cutting.

The recent developments in material sciences and rational structural designs have advanced the field of compliant and deformable electronics systems. However, many of these systems are limited in either overall stretchability or areal coverage of functional components. Here, we design a construct inspired by Kirigami for highly deformable micro-supercapacitor patches with high areal coverages of electrode and electrolyte materials. These patches can be fabricated in simple and efficient steps by laser-assisted graphitic conversion and cutting. Because the Kirigami cuts significantly increase structural compliance, segments in the patches can buckle, rotate, bend and twist to accommodate large overall deformations with only a small strain (&lt;3%) in active electrode areas. Electrochemical testing results have proved that electrical and electrochemical performances are preserved under large deformation, with less than 2% change in capacitance when the patch is elongated to 382.5% of its initial length. The high design flexibility can enable various types of electrical connections among an array of supercapacitors residing in one patch, by using different Kirigami designs

Use of a cAMP BRET Sensor to Characterize a Novel Regulation of cAMP by the Sphingosine 1-Phosphate/G13 Pathway

Regulation of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) is integral in mediating cell growth, cell differentiation, and immune responses in hematopoietic cells. To facilitate studies of cAMP regulation we developed a BRET (bioluminescence resonance energy transfer) sensor for cAMP, CAMYEL (cAMP sensor using YFP-Epac-RLuc), which can quantitatively and rapidly monitor intracellular concentrations of cAMP in vivo. This sensor was used to characterize three distinct pathways for modulation of cAMP synthesis stimulated by presumed Gs-dependent receptors for isoproterenol and prostaglandin E2. Whereas two ligands, uridine 5'-diphosphate and complement C5a, appear to use known mechanisms for augmentation of cAMP via Gq/calcium and Gi, the action of sphingosine 1-phosphate (S1P) is novel. In these cells, S1P, a biologically active lysophospholipid, greatly enhances increases in intracellular cAMP triggered by the ligands for Gs-coupled receptors while having only a minimal effect by itself. The enhancement of cAMP by S1P is resistant to pertussis toxin and independent of intracellular calcium. Studies with RNAi and chemical perturbations demonstrate that the effect of S1P is mediated by the S1P2 receptor and the heterotrimeric G13 protein. Thus in these macrophage cells, all four major classes of G proteins can regulate intracellular cAMP