Tarantula Hairs as Corneal Foreign Bodies

Purpose: To report a case of tarantula hairs found in the cornea and discuss treatment. Case Report: A 16-year-old male presented with a 6-week history of right ocular irritation that began after letting his pet tarantula crawl on his face. Slit-lamp examination of the right eye revealed the presence of approximately 16 dark foreign bodies that had the appearance of small hairs. The foreign bodies were removed from the nasal region of the right cornea using Jewelers forceps, and the patient was prescribed a combination neomycin, polymyxin B, and dexamethasone ointment (Maxitrol®), given 4 times per day. Results: The patient presented for follow-up 2 weeks later, with resolution of symptoms. Conclusion: Effective treatment of keratitis caused by tarantula hairs includes taking a detailed history, conducting a careful slit-lamp examination, removal of any accessible hairs, and initiation of treatment with a topical steroid as determined by the clinical picture

The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer. METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each injection. RESULTS: Deaths from metastasis were much lower in the pesVEGFR-2 and pEndo groups than in those of the pVec. Tumor volume was significantly lower in the pesVEGFR-2 and the pEndo groups throughout the study. Multiplicity of lymph node and lung metastatic nodules was significantly suppressed in the pesVEGFR-2 and pEndo groups. Moreover, the total number of overall metastasis including the other organs was also decreased in these groups. However, pesVEGFR-2 was not able to decrease the number of lungs, ovaries, kidneys and adrenals with metastasis as counted by unilateral or bilateral metastasis. The number of CD34+/Lyve-1⁻ blood microvessels was significantly decreased in the pEndo group, while the number of CD34⁻/Lyve-1+ lymphatic vessels was significantly decreased in the pesVEGFR-2 and pEndo groups. In addition, a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells was observed in the pesVEGFR-2 and pEndo groups. Levels of apoptosis were significantly increased in the pEndo group, whereas the rates of cell proliferation were significantly decreased in the pesVEGFR-2 and pEndo groups. CONCLUSIONS: Our data demonstrate that esVEGFR-2 can inhibit mainly lymph node metastasis. The antimetastatic activity of esVEGFR-2 may be of high clinical significance in the treatment of metastatic breast cancer because lymph node involvement is a most important prognostic factor in cancer patients

cGAS Drives Noncanonical-Inflammasome Activation in Age-Related Macular Degeneration

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness

Repurposing Anti-Inflammasome NRTIs for Improving Insulin Sensitivity and Reducing Type 2 Diabetes Development

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P \u3c 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes

Variational water-wave model with accurate dispersion and vertical vorticity

A new water-wave model has been derived which is based on variational techniques and combines a depth-averaged vertical (component of) vorticity with depth-dependent potential flow. The model facilitates the further restriction of the vertical profile of the velocity potential to n-th order polynomials or a finite-element profile with a small number of elements (say), leading to a framework for efficient modeling of the interaction of steepening and breaking waves near the shore with a large-scale horizontal flow. The equations are derived from a constrained variational formulation which leads to conservation laws for energy, mass, momentum and vertical vorticity. It is shown that the potential-flow water-wave equations and the shallow-water equations are recovered in the relevant limits. Approximate shock relations are provided, which can be used in numerical schemes to model breaking waves

Retinal Angiogenesis Suppression through Small Molecule Activation of p53

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies

Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis

OBJECTIVE: Antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) characterize a limbic encephalitis (LE) strongly associated with HLA-DRB1*07:01, although some patients lack LGI1-Abs in CSF or do not carry this allele. Whether they represent a different subtype of disease or have different prognoses is unclear. METHODS: Retrospective analysis of clinical features, IgG isotypes, and outcome according to LGI1-Ab CSF positivity and DRB1*07:01 in a cohort of anti-LGI1 LE patients. RESULTS: Patients with LGI1-Abs detected in both CSF and serum (105/134, 78%) were compared with those who were CSF negative (29/134, 22%). Both groups had similar clinical features and serum levels, but CSF-positive patients had shorter diagnostic delay, more frequently hyponatremia, inflammatory CSF, and abnormal MRI (p 0.05). HLA and IgG isotypes were not associated with poor outcome (mRS >2 at last follow-up) in univariate analyses; CSF positivity was only identified as a poor outcome predictor in the multivariate analysis including the complete follow-up, whereas age and female sex also remained when just the first year was considered. CONCLUSIONS: LE without CSF LGI1-Abs is clinically indistinguishable and likely reflects just a lesser LGI1-Ab production. HLA association is sex and age biased and presents clinical particularities, suggesting subtle differences in the immune response. Long-term outcome depends mostly on demographic characteristics and the intensity of the intrathecal synthesis

Broadband metamaterial for nonresonant matching of acoustic waves

Unity transmittance at an interface between bulk media is quite common for polarized electromagnetic waves incident at the Brewster angle, but it is rarely observed for sound waves at any angle of incidence. In the following, we theoretically and experimentally demonstrate an acoustic metamaterial possessing a Brewster-like angle that is completely transparent to sound waves over an ultra-broadband frequency range with >100% bandwidth. The metamaterial, consisting of a hard metal with subwavelength apertures, provides a surface impedance matching mechanism that can be arbitrarily tailored to specific media. The nonresonant nature of the impedance matching effectively decouples the front and back surfaces of the metamaterial allowing one to independently tailor the acoustic impedance at each interface. On the contrary, traditional methods for acoustic impedance matching, for example in medical imaging, rely on resonant tunneling through a thin antireflection layer, which is inherently narrowband and angle specific

The threshold hypothesis revisited: bilingual lexical knowledge and non-verbal IQ development

The threshold hypothesis (Cummins 1976 et passim) is one of the most influential theoretical frameworks on the relation between bilingualism and cognition. The aim of our study is to contribute towards an operationalisation of the threshold hypothesis. We analyse data from 100 Turkish-English successive bilingual children and from their parents, and investigate the relation between bilingualism and cognition. When compared with monolingual control groups, the bilinguals in our study have smaller vocabulary sizes in both languages. However, when both vocabularies are taken together and the total conceptual vocabulary is computed no bilingual disadvantage can be identified. Children with parental support for L1 outperform the monolingual control groups in our study in terms of non-verbal intelligence scores. The originality of the present study resides in the fact that, to our knowledge, for the first time parental support for L1 and dominance in L1 is linked to the cognitive development of the children