Analysis of copper(II) using the ascorbate/oxygen system – a valuable undergraduate resource

In deionised water, ascorbic acid (AH−), through oxidation by oxygen in the presence of copper(II), was found to degrade with zero-order kinetics. The magnitude of the reaction rate varied directly with the copper(II) concentration. At a higher pH (7.4), the same reaction was found to be pseudo-first order. Once again, the magnitude of the rate increased linearly with copper(II) concentration at a micromolar level. Dissolved oxygen levels, in excess AH− and trace copper(II), displayed similar kinetics under both conditions. Monitoring of either AH− levels or dissolved oxygen concentration was found to be a useful novel undergraduate practical laboratory for trace copper(II) determination. Students can measure the kinetics for standards and their unknown copper solution and quantitate the unknown copper

Purkinje cell injury, structural plasticity and fusion in patients with Friedreich's ataxia

Purkinje cell pathology is a common finding in a range of inherited and acquired cerebellar disorders, with the degree of Purkinje cell injury dependent on the underlying aetiology. Purkinje cells have an unparalleled resistance to insult and display unique regenerative capabilities within the central nervous system. Their response to cell injury is not typical of most neurons and likely represents both degenerative, compensatory and regenerative mechanisms. Here we present a pathological study showing novel and fundamental insights into Purkinje cell injury, remodelling and repair in Friedreich’s ataxia; the most common inherited ataxia. Analysing post-mortem cerebellum tissue from patients who had Friedreich's ataxia, we provide evidence of significant injury to the Purkinje cell axonal compartment with relative preservation of both the perikaryon and its extensive dendritic arborisation. Axonal remodelling of Purkinje cells was clearly elevated in the disease. For the first time in a genetic condition, we have also shown a disease-related increase in the frequency of Purkinje cell fusion and heterokaryon formation in Friedreich's ataxia cases; with evidence that underlying levels of cerebellar inflammation influence heterokaryon formation. Our results together further demonstrate the Purkinje cell’s unique plasticity and regenerative potential. Elucidating the biological mechanisms behind these phenomena could have significant clinical implications for manipulating neuronal repair in response to neurological injury

Correction to Fully Enclosed Microfluidic Paper-Based Analytical Devices

There is an error in the units of the concentrations of potassium iodide and trehalose described in the experimental details on page 1581. The correct concentrations are 0.6 M potassium iodide and 0.3 M trehalose

Fully Enclosed Microfluidic Paper-Based Analytical Devices

This article introduces fully enclosed microfluidic paper-based analytical devices (microPADs) fabricated by printing toner on the top and bottom of the devices using a laser printer. Enclosing paper-based microfluidic channels protects the channels from contamination, contains and protects reagents stored on the device, contains fluids within the channels so that microPADs can be handled and operated more easily, and reduces evaporation of solutions from the channels. These benefits extend the capabilities of microPADs for applications as low-cost point-of-care diagnostic devices

Assessment of myofascial pain syndrome among married female healthcare workers: a cross sectional comparative study in a tertiary care centre

Background: Myofascial pain syndrome (MPS) is common among females between ages 20-40 years. Psychosomatic and mechanical reasons are attributed as causative factors. Female health care workers (FHW) in hospitals with rapid patient turn over are vulnerable to develop MPS. Our aim was to ascertain the prevalence of MPS in married FHW working in various departments of the hospital and its association with poor sleep and work stress. Methods: We selected married FHWs in 20-50 years age group and divided them into two groups, medical and paramedical (those involved directly and indirectly with patient care respectively). MPS was diagnosed after detailed personal interview and clinical examination. Sleep duration was divided into less than 5 hours and more than 5hours. Presence of work-related stress and other medical parameters were also recorded. Results: A total of 150 medical and 150 paramedical FHWs were included in the study. Overall prevalence of MPS among FHWs was 42%, of which, medical group was 32% and paramedical was 52%. The paramedical group showed significantly higher prevalence of MPS (p: 0.02). Sleep was less than 5 hours in 29.3% of medical FHW and 13.3% of paramedical. This difference didn’t show any association to MPS (p=0.8). 38% FHW perceived excessive work stress, 40% were paramedical and 36% were medical. This didn’t correlate with prevalence of MPS (p=0.2) among them. Conclusions: Paramedical FHW experienced more MPS than medical and it was more of mechanical type and not due to work stress or sleep deprivation

Niemann–Pick type C disease as proof-of-concept for intelligent biomarker panel selection in neurometabolic disorders

AIM: Using Niemann-Pick type C disease (NPC) as a paradigm, we aimed to improve biomarker discovery in patients with neurometabolic disorders. METHOD: Using a multiplexed liquid chromatography tandem mass spectrometry dried bloodspot assay, we developed a selective intelligent biomarker panel to monitor known biomarkers N-palmitoyl-O-phosphocholineserine and 3β,5α,6β-trihydroxy-cholanoyl-glycine as well as compounds predicted to be affected in NPC pathology. We applied this panel to a clinically relevant paediatric patient cohort (n = 75; 35 males, 40 females; mean age 7 years 6 months, range 4 days-19 years 8 months) presenting with neurodevelopmental and/or neurodegenerative pathology, similar to that observed in NPC. RESULTS: The panel had a far superior performance compared with individual biomarkers. Namely, NPC-related established biomarkers used individually had 91% to 97% specificity but the combined panel had 100% specificity. Moreover, multivariate analysis revealed long-chain isoforms of glucosylceramide were elevated and very specific for patients with NPC. INTERPRETATION: Despite advancements in next-generation sequencing and precision medicine, neurological non-enzymatic disorders remain difficult to diagnose and lack robust biomarkers or routine functional testing for genetic variants of unknown significance. Biomarker panels may have better diagnostic accuracy than individual biomarkers in neurometabolic disorders, hence they can facilitate more prompt disease identification and implementation of emerging targeted, disease-specific therapies

Primary care provider–reported involvement in breast cancer treatment decisions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149227/1/cncr31998.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149227/2/cncr31998_am.pd

The transcription factor PPARα is overexpressed and is associated with a favourable prognosis in IDH-wildtype primary glioblastoma

© 2016 John Wiley & Sons Ltd Aims: PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma datasets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients’ clinicopathological features and other molecular markers associated with gliomagenesis. Methods and results: With protein immunoblotting techniques and reverse transcription quantitative real-time PCR, PPARα was found to be significantly overexpressed in glioblastoma compared with control brain tissue (P = 0.032 and P = 0.005). PPARA gene expression was found to be enriched in the classical glioblastoma subtype within The Cancer Genome Atlas (TCGA) dataset. Although not associated with overall survival when assessed by immunohistochemistry, cross-validation with the TCGA dataset and multivariate analyses identified PPARA gene expression as an independent prognostic marker for overall survival (P = 0.042). Finally, hierarchical clustering revealed novel, significant associations between high PPARA expression and a putative set of glioblastoma molecular mediators including EMX2, AQP4, and NTRK2. Conclusions: PPARα is overexpressed in primary glioblastoma and high PPARA expression functions as an independent prognostic marker in the glioblastoma TCGA dataset. Further studies are required to explore genetic associations with high PPARA expression and to analyse the predictive role of PPARα expression in glioblastoma models in response to PPARα agonists

The rheumatoid synovial environment alters fatty acid metabolism in human monocytes and enhances CCL20 secretion

Objectives: Fatty acid oxidation (FAO) and glycolysis have been implicated in immune regulation and activation of macrophages. However, investigation of human monocyte intracellular metabolism in the context of the hypoxic and inflammatory rheumatoid arthritis (RA) synovium is lacking. We hypothesized that exposure of monocytes to the hypoxic and inflammatory RA environment would have a profound impact on their metabolic state, and potential to contribute to disease pathology. Methods: Human monocytes were isolated from buffy coats and exposed to hypoxia. Metabolic profiling of monocytes was carried out by LC-MS metabolomics. Inflammatory mediator release after LPS or RA-synovial fluid (RA-SF) stimulation was analysed by ELISA. FAO was inhibited by etomoxir or enhanced with exogenous carnitine supplementation. Transcriptomics of RA blood monocytes and RA-SF macrophages was carried out by microarray. Results: Hypoxia exacerbated monocyte-derived CCL20 and IL-1β release in response to LPS, and increased glycolytic intermediates at the expense of carnitines. Modulation of carnitine identified a novel role for FAO in the production of CCL20 in response to LPS. Transcriptional analysis of RA blood monocytes and RA-SF macrophages revealed that fatty acid metabolism was altered and CCL20 increased when monocytes enter the synovial environment. In vitro analysis of monocytes showed that RA-SF increases carnitine abundance and CCL20 production in hypoxia, which was exacerbated by exogenous carnitine. Conclusion: This work has revealed a novel inflammatory mechanism in RA that links FAO to CCL20 production in human monocytes, which could subsequently contribute to RA disease pathogenesis by promoting the recruitment of Th17 cells and osteoclastogenesis

The Lantern Vol. 37, No. 1, Fall 1970

• Circumstance • Advice • For What You Do For Me • Blink • Love • Love II • Magic • To Be a Child • A Year Later • A Poem in February • The Crystal Brick Road • Ephemera • Life • Whiskers • Thoughts On Being Sick • A Non-Poem • A Gruk Anthology • Moon • A Thought • Dwarf in an Existential Dawn • Corridors To My Mind • Sadness • The Enzyme Song • Creatures of Sandhttps://digitalcommons.ursinus.edu/lantern/1098/thumbnail.jp