Direct activation of transient receptor potential V1 by nickel ions

TRPV1 is a member of the transient receptor potential (TRP) family of cation channels. It is expressed in sensory neurons of the dorsal root and trigeminal ganglia as well as in a wide range of non-neuronal tissues. The channel proteins serve as polymodal receptors for various potentially harmful stimuli to prevent tissue damage by mediating unpleasant or painful sensations. Using Ca imaging and voltage-clamp recordings, we found that low millimolar doses of Ni²⁺ (NiSO₄) are able to induce non-specific cation currents in a capsaicin-sensitive population of cultured mouse trigeminal ganglion neurons. In addition, we show that NiSO₄ elicits intracellular Ca²⁺ transients and membrane currents in HEK293 and CHO cells heterologously expressing rat TRPV1. The use of voltage ramps from ?100 to +100 mV revealed a strong outward rectification of these currents. Application of NiSO₄ to the cytoplasmic face of inside-out membrane patches did not induce any currents. However, delivering NiSO₄ to the extracellular face during outside-out recordings, we observed a significant increase in open probability paralleled by a decrease in channel conductance. When combined with other TRPV1 agonists, NiSO₄ produces a bimodal effect on TRPV1 activity, depending on the strength and concentration of the second stimulus. Outwardly directed currents induced by low doses of capsaicin and nearly neutral pH values (～pH?=?7.0–6.5) were augmented by low doses of NiSO₄. In contrast, responses to stronger stimuli were reduced by NiSO₄. Moreover, we were able to identify amino acids involved in the effect of NiSO₄ on TRPV1.     

Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia

A pilot study previously demonstrated that thrice-weekly, fractionated-dose intravenous rituximab (RTX) limits CD20 loss from chronic lymphocytic leukemia (CLL) B cells, thereby enhancing immunotherapeutic targeting. Here, we investigated the feasibility of giving 20 mg rituximab subcutaneously thrice weekly for up to 12 weeks in 4 previously treated CLL patients. Subcutaneous rituximab was well-tolerated with minimal injection site reactions; a variable degree of efficacy was observed, likely influenced by the size of the patients’ B cell/CD20 burden. Subcutaneous RTX largely preserved CD20 expression on leukemic cells but the most effective therapeutic dosing regimen needs to be established (ClinicalTrials.gov Identifier: NCT00366418).     

A Cloud With a Silver Lining: Helping Students Learn About Professionalism

Problem: Educators face many challenges in teaching professionalism. Despite attempts to define professionalism, it remains abstract for students and often not fully appreciated until they are in clinic. Without a way to make it personally relevant, students will likely be less motivated to learn. Intervention: We used student-generated word clouds to facilitate reflection and discussions, thereby helping students make their perceptions of professionalism more explicit. Group discussion was followed by a 5-minute written reflection. Word clouds created in Semesters 1 and 7 enabled students to compare perceptions at two points in the curriculum. Context: The George Washington University Doctor of Physical Therapy Program is a 3-year, 8-semester, 109-credit postgraduate program that includes 34 weeks of clinical practice. Reflection is foundational to the curriculum, and students reflect on their learning and professional growth each semester. Historically, students were introduced to professionalism in Semester 1 using explicit instructional strategies. Despite the wealth of resources, readings, and discussions, engagement remained challenging. Outcome: Student-generated word clouds created a personally relevant visual from which uniquely designed prompts were created to facilitate discussion. Having students compare word clouds across semesters enabled them to identify what, when, how, and where they learned about professionalism. Word clouds, categorized words, and 5-minute written reflections provided evidence of individual and collective changes in student perceptions. Lessons Learned: Students will engage in rich discussions on professionalism if it is personally relevant. Anonymity can foster discussion on personal characteristics and biases. Visualization of student-generated, narrative data enhanced reflection and discussion. Comparing word clouds from two points in time helped students articulate changes in their perceptions of professionalism. A 5-minute reflection can be a powerful learning tool for students and faculty. Outcomes demonstrated the value of designing interventions grounded in the educational principles.     

Representations of workers with hearing loss in Canadian newspapers: a thematic analysis

Objective: Participation in the labour force with a hearing impairment presents a number of challenges. This study describes how Canadian newspapers represent workers with hearing loss. Design: Taking a critical framing theory approach, thematic analysis was performed through coding relevant articles, abstracting and hierarchically categorising themes. Study sample: Seven English-language Canadian newspapers were searched for publications between 1995 and 2016. Twenty-six articles met our criteria: discussing paid workers with hearing loss who used English rather than sign language on the job and making reference to workers’ competence. Results: We identified a global theme, Focussing on a good worklife or focussing on a limited worklife, composed of three organising themes (1) Prominent individuals struggle, take action, and continue despite hearing loss, (2) Workers with hearing loss in the community create their best day themselves, and (3) Workers with hearing loss, as a generalised whole, are portrayed as either competent or limited. Conclusions: The dominant framing portrays individual workers as ingenious, determined, and successful. Negative framings were predominantly generalisations to these workers as a group. To generate more positive framings, professionals can build relationships with consumer groups and, when contacted by the media, direct journalists to interview workers with hearing loss.     

Landscape and children’s health: Old natures and new challenges for the preventorium

Preventoria were established in the early part of the twentieth century at fresh air sites away from cities for the purposes of rest cures for children, usually for those who were at risk of contracting tuberculosis. This paper discusses preventoria in relation to their general landscapes, and outlines the types of landscapes in which preventoria are found, namely woods and forests, ocean, rivers and lakes, and agricultural settings. The preventorium movement is placed in historical landscape context, with urban planning, national parks, and other nineteenth century trends. Fresh air was the driving force of both treatment and locations of preventoria and sanatoria. Current movements in child health to combat obesity and ‘nature-deficit-disorder’ also call for greater engagement with fresh air, and stress the therapeutic value of natural landscape.Australia’s oldest preventorium is examined as a case study of preventoria and the challenges which old preventoria are facing today to re-invent themselves in predominantly rural landscapes.     

Cloning and characterization of voltage‐gated calcium channel alpha1 subunits in Xenopus laevis during development

Voltage‐gated calcium channels play a critical role in regulating the Ca²⁺ activity that mediates many aspects of neural development, including neural induction, neurotransmitter phenotype specification, and neurite outgrowth. Using Xenopus laevis embryos, we describe the spatial and temporal expression patterns during development of the 10 pore‐forming alpha1 subunits that define the channels' kinetic properties. In situ hybridization indicates that Ca_V1.2, Ca_V2.1, Ca_V2.2, and Ca_V3.2 are expressed during neurula stages throughout the neural tube. These, along with Ca_V1.3 and Ca_V2.3, beginning at early tail bud stages, and Ca_V3.1 at late tail bud stages, are detected in complex patterns within the brain and spinal cord through swimming tadpole stages. Additional expression of various alpha1 subunits was observed in the cranial ganglia, retina, olfactory epithelium, pineal gland, and heart. The unique expression patterns for the different alpha1 subunits suggests they are under precise spatial and temporal regulation and are serving specific functions during embryonic development. Developmental Dynamics 238:2891–2902, 2009. © 2009 Wiley‐Liss, Inc.