Neurogenic Inflammation of Guinea-Pig Bladder

Capsaicin, substance P, and ovalbumin, instilled into the bladders of naive and ovalbumin (OVA) sensitized guineapigs caused inflammation, as indicated by increased vascular permeability. Histological changes after exposure to these compounds progressed with time from intense vasodilatation to marginalization of granulocytes followed by interstitial migration of leukocytes. In vitro incubation of guinea-pig bladder tissue with substance P and ovalbumin stimulated release of prostaglandin D2 and leukotrienes. In vitro incubation of bladder tissue with capsaicin, OVA, prostaglandin D2, leukotriene C4, histamine, or calcium ionophore A-23587 all stimulated substance P release. These data suggest that bladder inflammation initiated by a variety of stimuli could lead to a cyclic pattern of release of inflammatory mediators and neuropeptides, which could result in amplification and persistence of cystitis after the inciting cause has subsided

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making

Taming Atomic Defects for Quantum Functions

Single atoms provide an ideal system for utilizing fundamental quantum functions. Their electrons have well-defined energy levels and spin properties. Even more importantly, for a given isotope -- say, $^{12}$C -- all the atoms are identical. This creates a perfect uniformity that is impossible to achieve in macroscopic-size quantum systems. However, herding individual atoms is a very difficult task that requires trapping them with magnetic or optical means and cooling them down to temperatures in the nanokelvin range. On the other hand, the counterpart of single atoms -- the single defects -- may be as good as atom-based quantum systems if not better. These defects, also referred as quantum defects, possess the favorable energy, spin, and uniformity properties of single atoms and remain in their place without the help of precisely tuned lasers. While the number of usable isotopes is set, the combinations of defects and their host material are practically limitless, giving us the flexibility to create precisely designed and controlled quantum systems. Furthermore, as we tame these defects for the quantum world, we bring about transformative opportunities to the classical world in forms such as ultradense electronic devices and precise manufacturing. In this research insight, we introduce some of our recent work on precisely controlled creation and manipulation of individual defects with a scanning tunneling microscope (STM). We also discuss possible pathways for utilizing these capabilities for the development of novel systems for Quantum Information Science (QIS) applications such as quantum information processing and ultrasensitive sensors

Towards the development of teachers for the future

The purpose of this research was to examine student teachers’ views on the kind of teachers they would like to be. The participants were 51 student teachers at the primary education department of a state university. The views of these student teachers were collected from unstructured reports that they submitted following a one-semester classroom management course in the 5th semester. The qualitative data gained from the reports, specifically the attributes that the student teachers associated with themselves, were analysed in terms of classroom management according to Korthegan’s Onion Model using a qualitative content analysis method. The data demonstrate that the participants expressed their opinions mostly regarding classroom environment, behaviour and competency. The reports also present their views about the kind of teachers they would grow into and the teacher behaviour they would like to adopt. The results of the study reveal that the student teacher participants were at the levels of interventionist and interventionist/interactionist control; 2 different approaches to dynamic assessment and classroom management styles. They also used authoritative, educational, behaviour-based, and democratic approaches. The study suggests that, in order for the student teachers to express themselves about their teaching in the layers of belief, identity and mission (inner layers) of the Onion Model, they must be provided with opportunities and experiences. Keywords: classroom management; Korthegan’s Onion Model; student teachers; teacher development; teacher educatio

IMPLEMENTASI MODEL DISCOVERY LEARNING UNTUK MENINGKATKAN KEMAMPUAN LITERASI SAINS SISWA KELAS XI MAN 2 HALMAHERA UTARA

Literasi sains merupakan instrument bagi siswa guna melatih kemampuan berpikir ilmiah siswa dalam usaha mengatasi masalah dalam kehidupan sehari-hari. Penggunaan model discovery learning mampu meningkatkan kemampuan literasi sains. Kemampuan literasi sains dapat dikembangkan atau dimunculkan pada diri siswa saat proses pembelajaran dengan menggunakan berbagai model dan strategi pembelajaran yang memungkinkan untuk hal tersebut. Salah satu  model yang diharapkan dapat meningkatkan kemampuan literasi sains siswa adalah model discovery learning. Model discovery learning sesuai tujuan penggunaannya diharapkan dapat membantu siswa melatih kemampuan berbagi pengetahuan yang dimiliki dan menggunakan idenya untuk memecahkan masalah yang dipelajari. Penelitian ini dilaksanakan di Madrasah Aliyah Negeri 2 Halmahera Utara pada siswa kelas XI IPA-1 dengan jumlah siswa sebanyak 27 siswa. Jenis penelitiannya adalah penelitian deskriptif kuantitatif. Instrumen yang digunakan untuk memperoleh data kemampuan literasi sains adalah soal-soal tes yang sesuai dengan materi atau konsep yang diajarkan dan disesuaikan dengan indikator literasi sains. Analisis data dilakukan dengan analisis deskriptif dan inferensial. Berdasarkan hasil analisis data diperoleh kemampuan literasi sains siswa kelas XI  pada aspek konten meningkat sebesar 22,22 %, aspek proses atau kompetensi meningkat sebesar 29,63%,  dan aspek konteks meningkat sebesar 25,93%. Hasil analisis dengan menggunakan N-Gain untuk melihat peningkatan kemampuan literasi sains siswa menunjukkan bahwa secara rata-rata kemampuan literasi sains siswa berada pada kategori sedang yaitu sebanyak 81,48 %, kategori tinggi 11,11% dan kategori rendah 7,41 %. Dari hasil tersebut dapat dikatakan bahwa penggunaan model discovery learning dapat meningkatkan kemampuan literasi sains siswa kelas XI IPA MAN 2 Halmahera Utara. 

Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs). Methods: An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results: The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2). In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation driving 8 transcripts, which includes those involved in cancer (EYA1, Trail, HSF1, and ELK-1), smooth-to-skeletal muscle trans-differentiation, and Z01, a tight-junction protein, expression. Electrophoretic mobility shift assays confirmed that, in the mouse urinary bladder, activation of NK1R by substance P (SP) induces both NKx-2.5 and NF-kappaB translocations. Conclusion: This is the first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the unique discriminator of NK1R-modulated inflammation, it can be imagined that in the near future, new based therapies selective for controlling Nkx2.5 activity in the urinary tract may be used in the treatment in a number of bladder disorders

Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Summary of the LHC Controls and Operations Forum held at CERN on 1-2 December 1999

The LHC Controls-Operations Forum in December attempted to identify the challenges of running the LHC and the implications for controls and equipment. An outline of the forum, its objectives, summaries of the various sessions, conclusions and some recommendations are presented. It is anticipated that this information will act as input into current and future development

Measurement invariance of the kidney disease and quality of life instrument (KDQOL-SF) across Veterans and non-Veterans

<p>Abstract</p> <p>Background</p> <p>Studies have demonstrated that perceived health-related quality of life (HRQOL) of patients receiving hemodialysis is significantly impaired. Since HRQOL outcome data are often used to compare groups to determine health care effectiveness it is imperative that measures of HRQOL are valid. However, valid HRQOL comparisons between groups can only be made if instrument invariance is demonstrated. The Kidney Disease Quality of Life-Short Form (KDQOL-SF) is a widely used HRQOL measure for patients with chronic kidney disease (CKD) however, it has not been validated in the Veteran population. Therefore, the purpose of this study was to examine the measurement invariance of the KDQOL-SF across Veterans and non-Veterans with CKD.</p> <p>Methods</p> <p>Data for this study were from two large prospective observational studies of patients receiving hemodialysis: 1) Veteran End-Stage Renal Disease Study (VETERAN) (N = 314) and 2) Dialysis Outcomes and Practice Patterns Study (DOPPS) (N = 3,300). Health-related quality of life was measured with the KDQOL-SF, which consists of the SF-36 and the Kidney Disease Component Summary (KDCS). Single-group confirmatory factor analysis was used to evaluate the goodness-of-fit of the hypothesized measurement model for responses to the subscales of the KDCS and SF-36 instruments when analyzed together; and given acceptable goodness-of-fit in each group, multigroup CFA was used to compare the structure of this factor model in the two samples. Pattern of factor loadings (configural invariance), the magnitude of factor loadings (metric invariance), and the magnitude of item intercepts (scalar invariance) were assessed as well as the degree to which factors have the same variances, covariances, and means across groups (structural invariance).</p> <p>Results</p> <p>CFA demonstrated that the hypothesized two-factor model (KDCS and SF-36) fit the data of both the Veteran and DOPPS samples well, supporting configural invariance. Multigroup CFA results concerning metric and scalar invariance suggested partial strict invariance for the SF-36, but only weak invariance for the KDCS. Structural invariance was not supported.</p> <p>Conclusions</p> <p>Results suggest that Veterans may interpret the KDQOL-SF differently than non-Veterans. Further evaluation of measurement invariance of the KDQOL-SF between Veterans and non-Veterans is needed using large, randomly selected samples before comparisons between these two groups using the KDQOL-SF can be done reliably.</p