In vitro modulation of inflammatory cytokine and IgG levels by extracts of Perna canaliculus

BACKGROUND: Inflammation is a predominant characteristic of autoimmune diseases which is characterized by the increased expression of pro-inflammatory cytokines. Soon to be published work from our laboratory has shown that ingestion of Perna canaliculus prevents the development of autoimmune diseases such as Systemic Lupus Erythematosus and rheumatoid arthritis in laboratory animals. The current paper attempts to illustrate how Perna can alleviate inflammation by modulating inflammatory cytokines, cyclooxygenase enzymes and Immunoglobulin-G (IgG) levels. METHODS: In the present study, hydrochloric acid [HCl] and Tween-20 were used to develop extracts of Perna. These extracts were assayed for protein content. Increasing concentrations of these extracts were then tested in cell culture for modulation of inflammatory cytokine, cyclooxygenase enzymes and IgG levels. Parallel tests were run using an available glycogen extract of Perna as a comparison to our in-house laboratory preparations. RESULTS: Tween-20 Perna extracts were found to be more stable and less toxic in cell culture than HCl digest of Perna. They also assayed higher in protein content that HCl extracts. Although both extracts inhibited IgG production in V2E9 hybridomas, Tween-20 extracts were more consistent in IgG suppression than HCl extracts. Overall Tween-20 extracts effectively decreased levels of TNF-α, IL-1, IL-2 and IL-6 as observed using cytokine bioassays. Twenty micrograms of Tween-20 Perna extracts induced such significant decreases in inflammatory cytokine production that when tested on sensitive cell lines, they very nearly abolished the decrease in viability induced by these cytokines. Tween-20 extracts effectively inhibited both COX-1 and COX-2 cyclooxygenase activity. As a comparison, the glycogen extract also demonstrated a similar though weaker effect on COX-1 and COX-2 enzymes. The active components of both extracts (Tween-20 and glycogen) were observed to possess molecular weights above 100 kDa. Although the anti-cytokine activity of the Tween-20 extract was destroyed by Proteinase-K treatment, the anti-COX-1 and anti-COX-2 activity of both the extracts were not sensitive to protease treatment. CONCLUSION: We have successfully demonstrated modulation in the levels of inflammatory cytokines, cyclooxygenase enzymes and immunoglobulins by our in-house laboratory preparations of Perna canaliculus, whereby suggesting an immunomodulatory role of Perna canaliculus in regulating inflammation

Assessing the Quality of Clinical Teachers: A Systematic Review of Content and Quality of Questionnaires for Assessing Clinical Teachers

BACKGROUND: Learning in a clinical environment differs from formal educational settings and provides specific challenges for clinicians who are teachers. Instruments that reflect these challenges are needed to identify the strengths and weaknesses of clinical teachers. OBJECTIVE: To systematically review the content, validity, and aims of questionnaires used to assess clinical teachers. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and ERIC from 1976 up to March 2010. REVIEW METHODS: The searches revealed 54 papers on 32 instruments. Data from these papers were documented by independent researchers, using a structured format that included content of the instrument, validation methods, aims of the instrument, and its setting. Results : Aspects covered by the instruments predominantly concerned the use of teaching strategies (included in 30 instruments), supporter role (29), role modeling (27), and feedback (26). Providing opportunities for clinical learning activities was included in 13 instruments. Most studies referred to literature on good clinical teaching, although they failed to provide a clear description of what constitutes a good clinical teacher. Instrument length varied from 1 to 58 items. Except for two instruments, all had to be completed by clerks/residents. Instruments served to provide formative feedback ( instruments) but were also used for resource allocation, promotion, and annual performance review (14 instruments). All but two studies reported on internal consistency and/or reliability; other aspects of validity were examined less frequently. CONCLUSIONS: No instrument covered all relevant aspects of clinical teaching comprehensively. Validation of the instruments was often limited to assessment of internal consistency and reliability. Available instruments for assessing clinical teachers should be used carefully, especially for consequential decisions. There is a need for more valid comprehensive instruments

A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. A single ANF is modeled as a network of two exponential integrateand-fire point-neuron models, referred to as peripheral and central axons of the ANF. The peripheral axon is excited by the cathodic charge, inhibited by the anodic charge, and exhibits longer spike latencies than the central axon; the central axon is excited by the anodic charge, inhibited by the cathodic charge, and exhibits shorter spike latencies than the peripheral axon. The model also includes subthreshold and suprathreshold adaptive feedback loops which continuously modify the membrane potential and can account for effects of facilitation, accommodation, refractoriness, and spike-rate adaptation in ANF. Although the model is parameterized using data for either single or paired pulse stimulation with monophasic rectangular pulses, it correctly predicts effects of various stimulus pulse shapes, stimulation pulse rates, and level on the neural response statistics. The model may serve as a framework to explore the effects of different stimulus parameters on psychophysical performance measured in cochlear implant listeners

Loudness Adaptation in Acoustic and Electric Hearing

The present study is aimed to evaluate and compare loudness adaptation between normal hearing and cochlear-implant subjects. Loudness adaptation for 367-s pure tones was measured in five normal-hearing subjects at three frequencies (125, 1,000, and 8,000 Hz) and three levels (30, 60, and 90 dB SPL). In addition, loudness adaptation for 367-s pulse trains was measured in five Clarion cochlear-implant subjects at three stimulation rates (100, 991, and 4,296 Hz), three levels (10, 50, and 90% of the electric dynamic range), three stimulation positions (apical, middle and basal), and two stimulation modes (monopolar and bipolar). The method of successive magnitude estimation was used to quantify loudness adaptation. Similar to the previous results, we found that loudness adaptation in normal-hearing subjects increases with decreasing level and increasing frequency. However, we also found a small but significant loudness enhancement at 90 dB SPL in acoustic hearing. Despite large individual variability, we found that loudness adaptation in cochlear-implant subjects increases with decreasing levels, but is not significantly affected by the rate, place and mode of stimulation. A phenomenological model was proposed to predict loudness adaptation as a function of stimulus frequency and level in acoustic hearing. The present results were not fully compatible with either the restricted excitation hypothesis or the neural adaptation hypothesis. Loudness adaptation may have a central component that is dependent on the peripheral excitation pattern

Future physician-scientists: could we catch them young? Factors influencing intrinsic and extrinsic motivation for research among first-year medical students

The medical field is currently facing a physician-scientist shortage. One possible solution is to direct medical students towards a research oriented career. To do so, knowledge is needed on how to motivate medical students to do research. Therefore, this study examines motivation for research and identifies factors influencing intrinsic and extrinsic motivation for research among first-year medical students.\nFirst-year medical students were surveyed at the beginning of their bachelor's program in 2016. On a 7-point Likert scale, students reported their motivation for research, self-efficacy, perceptions of research, curiosity, and need for challenge. Regression analyses were used to examine the influence of these factors on students' motivation for research.\nOut of 316 approached students, 315 participated (99.7%). On average, students scored 5.49 on intrinsic, and 5.66 on extrinsic motivation for research. All factors measured influenced intrinsic and extrinsic motivation for research significantly and positively, also after adjusting for gender and age. Cumulative regression showed that these factors explained 39.6% of the variance in intrinsic, and 14% in extrinsic motivation for research.\nAll factors play an important role in intrinsic and, to a lesser extent, extrinsic motivation for research. First-year medical students' motivation for research could be enhanced by stimulating positive self-efficacy beliefs, positive perceptions of research, and curiosity. Also, it is important to fulfil students' needs for challenge by stimulating them to actively conduct research. Thus, to catch students young and cultivate physician-scientists, students should be stimulated to engage in research from the beginning of medical training.\nINTRODUCTION\nMETHODS\nRESULTS\nDISCUSSIONMerit, Expertise and Measuremen

Pathobiology and Immunobiology of Malignant Mesothelioma - Characterization of Tumor-Infiltrating Leukocytes and Cytokine Production in a Murine Model

Malignant mesothelioma (MM) is an aggressive, uniformly fatal serosal tumour, usually associated with asbestos exposure, for which there currently is no effective treatment. In order to gain insight into the mechanism(s) whereby MM might escape immune surveillance, a murine model for MM was used (a) to characterise the tumour-infiltrating lymphocytes (TIL) and macrophages (TIM) phenotypically, (b) to examine systemic immune recognition of MM, and (c) to examine the possible influence of tumour-derived cytokines on systemic and local pathobiological manifestations of MM. A profound down-regulation of lymphocyte surface markers, known to be involved in T cell activation, was found in TIL. Likewise, although TIM were present in large numbers, their expression of MHC class II antigen and integrins was weak or absent, suggestive of altered functional activity. Significant amounts of cytokines, in particular transforming growth factor beta, interleukin-6 (IL-6), IL-1 and tumour necrosis factor were produced during the course of MM tumour development directly by the MM cells and/or indirectly in response to tumour growth. These factors may contribute both to derangement of antitumour effector mechanisms and to the clinical and pathological manifestations of the disease