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

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 (<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

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

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

Functional characteristics of S-59 photochemically treated platelet concentrates derived from buffy coats

Background: A photochemical treatment (PCT) process for inactivation of infectious pathogens and leukocytes has been developed and evaluated using single-donor platelet concentrates. This study assessed the application of PCT to platelets prepared from pooled buffy coats. In this study, in vitro functional characteristics of PCT platelets were compared to control platelets prepared from pooled buffy coats using the approved platelet-additive solution T-Sol®. Platelets in platelet PAS III additive solution without PCT were evaluated as well. PCT also included the use of a psoralen (S-59) reduction device (SRD). Materials and Methods: Four types of platelet concentrates were compared: (1) platelet concentrate in plasma/T-Sol; (2) platelet concentrate in plasma/PAS III; (3) platelet concentrate in plasma/PAS III, PCT, 9 h SRD and (4) platelet concentrate in plasma/PAS III, PCT, 16 h SRD. PCT occurred on the day after whole-blood collection. In vitro assay parameters included: pH, pO 2, pCO 2, HCO 3,/ - platelet count, mean platelet volume, plasma glucose, plasma lactate, total ATP, expression of p-selectin, hypotonic shock response and electron microscopy. Results: The results indicate that PCT is compatible with platelet concentrates prepared from pooled buffy coats for up to 7 days of storage. Conclusion: The PCT process resulted in acceptable in vitro platelet functional characteristics and is currently in clinical trials to evaluate the haemostatic efficacy of PCT platelets in thrombocytopenic patients requiring multiple platelet transfusions. Copyrigh

Cluster-randomized, crossover trial of head positioning in acute stroke

The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P\u3c0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P = 0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P = 0.83). There were no significant betweengroup differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours

Large Orbital Pediatric Intraosseous Hemangioma

A five-year-old male presenting with progressive right facial swelling underwent multiple biopsies before being diagnosed with a polyostotic frontal-zygomatic primary intraosseous hemangioma. Intraosseous hemangiomas are rare, more frequently afflict adult females, and very rarely involve the orbit. Our case with bony destruction and surrounding soft tissue mass measured 5.3 cm in a child mimicked a more ominous malignancy. This case is unique with its rapid progression and largest reported size, leading to additional challenges such as difficulty in achieving an adequate tissue sample and in the surgical management with respect to significant blood loss in a small child