Corrective responses to perturbation applied during walking in humans

Modulation of the flexor reflex response during walking in humans following stimulation at 5 points in the step cycle was studied. At heel strike, an extensor response was observed at the ankle and the knee which would allow one to stabilize and plant the ipsilateral foot fast. Later on in the stance, there was a dorsiflexor and an extensor response at the ankle and the knee, respectively, which would result in the removal of the foot from the stimulus without collapsing at the knee. During mid-swing, a flexor reflex response was observed at the ankle and the hip joint. There was a tendency for the normal stride to be longer than the perturbed stride in mid swing and early stance while it was of shorter duration in late stance and early swing.     

Evaluation of funding gastroenterology research in Canada illustrates the beneficial role of partnerships

BACKGROUND:

Funders of health research in Canada seek to determine how their funding programs impact research capacity and knowledge creation.

OBJECTIVE:

To evaluate the impact of a focused grants and award program that was cofunded by the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes, and the Canadian Association of Gastroenterology; and to measure the impact of the Program on the career paths of funded researchers and assess the outcomes of research supported through the Program.

METHODS:

A survey of the recipients of grants and awards from 2000 to 2008 was conducted in 2012. The CIHR Funding Decisions database was searched to determine subsequent funding; a bibliometric citation analysis of publications arising from the Program was performed.

RESULTS:

Of 160 grant and award recipients, 147 (92%) completed the survey. With >$17.4 million in research funding, support was provided for 131 fellowship awards, seven career transition awards, and 22 operating grants. More than three-quarters of grant and award recipients continue to work or train in a research-related position. Combined research outputs included 545 research articles, 130 review articles, 33 book chapters and 11 patents. Comparative analyses indicate that publications supported by the funding program had a greater impact than other Canadian and international comparators.

CONCLUSIONS:

Continuity in support of a long-term health research funding partnership strengthened the career development of gastroenterology researchers in Canada, and enhanced the creation and dissemination of new knowledge in the discipline.     

Expression of calcitonin gene-related peptide,substance P and protein kinase C in cultured dorsal root ganglion neurons following chronic exposure to mu,delta and kappa opiates

The mechanisms involved in morphine tolerance are poorly understood. It was reported by our group that calcitonin gene-related peptide (CGRP)-like immunoreactivity (IR) was increased in the spinal dorsal horn during morphine tolerance [Ménard et al. (1996) J. Neurosci. 16, 2342-2351]. More recently, we observed that it was possible to mimic these results in cultured dorsal root ganglion (DRG) neurons allowing for more detailed mechanistic studies [Ma et al. (2000) Neuroscience 99, 529-539]. The aim of the present series of experiments was to further validate the DRG cell culture model by establishing which subtypes of opioid receptors are involved in the induction of CGRP in cultured rat DRG neurons, and to examine the signaling pathway possibly involved in the induction of CGRP-like IR following repeated opiate treatments. Other neuropeptides known to be expressed in DRG neurons, such as substance P (SP), neuropeptide Y (NPY) and galanin, were investigated to assess specificity. Following treatment with any of the three opioid agonists (mu, DAMGO; delta, DPDPE; kappa, U50488H), the number of CGRP- and SP-IR cultured DRG neurons increased significantly, and in a concentration-dependent manner, with the effects of kappa agonist being less pronounced. NPY and galanin were not affected.Double-immunofluorescence staining showed that the three opioid receptors were co-localized with both CGRP- and SP-like IR.Protein kinase C (PKC)-like IR was found to be significantly increased following a repetitive treatment with DAMGO. Double-immunofluorescence staining showed the co-localization of PKCalpha with CGRP- and SP-IR in cultured DRG neurons. Moreover, a combined treatment with DAMGO and a PKC inhibitor (chelerythrine chloride or G? 6976) was able to block the effects of the opioid on increased CGRP-like IR. These data suggest that the three opioid receptors may be involved in the induction of CGRP and SP observed following chronic exposure to opiates, and that PKC probably plays a role in the signaling pathway leading to the up-regulation of these neuropeptides. These findings further validate the DRG cell culture as a suitable model to study intracellular pathways that govern changes seen following repeated opioid treatments possibly leading to opioid tolerance.     

Oncocytic papillary renal cell carcinoma with solid architecture: mimic of renal oncocytoma

Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117–/PR– immunophenotype (feature shared by RCC). The CD117–/PR– ORCN also displayed α-methylacyl-coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.     

Mutations affecting spindle pole body and mitotic exit network function are synthetically lethal with a deletion of the nucleoporin NUP1 in S. cerevisiae

Nuclear pore complexes (NPCs) are embedded in the nuclear envelope of eukaryotic cells and function to regulate passage of macromolecules in and out of the nucleus. Nup1 is one of 30 nucleoporins comprising the NPC of the yeast Saccharomyces cerevisiae and is located on the nucleoplasmic face of the NPC where it plays a role in mRNA export and protein transport. In order to further characterize the function of Nup1 we used a genetic approach to identify mutations that are synthetically lethal in combination with a deletion of NUP1 (nup1Δ). We have identified one such nup1 lethal mutant (nle6) as a temperature sensitive allele of nud1. NUD1 encodes a component of the yeast spindle pole body (SPB) and acts as scaffolding for the mitotic exit network (MEN). We observe that nle6/nud1 mutant cells have a normal distribution of NPCs within the nuclear envelope and exhibit normal rates of nuclear protein import at both the permissive and restrictive temperatures. nup1Δ also exhibits synthetic lethality with bub2Δ and bfa1Δ, both of which encode proteins that colocalize with Nud1 at spindle pole bodies and function in the mitotic exit network. However, we do not observe genetic interactions among nle6/nud1, bub2Δ, or bfa1Δ and mutations in the nucleoporin encoding genes NUP60 or NUP170, nor is nup1Δ synthetically lethal with the absence of components downstream in the mitotic exit network, including Lte1, Swi5, and Dbf2. Our results suggest a novel functional connection between Nup1 and proteins comprising both the spindle pole body and early mitotic exit network.     

Indoor combustion and asthma

Indoor combustion produces both gases (eg, nitrogen dioxide, carbon monoxide) and particulate matter that may affect the development or exacerbation of asthma. Sources in the home include both heating devices (eg, fireplaces, woodstoves, kerosene heaters, flued [ie, vented] or nonflued gas heaters) and gas stoves for cooking. This article highlights the recent literature examining associations between exposure to indoor combustion and asthma development and severity. Since asthma is a chronic condition affecting both children and adults, both age groups are included in this article. Overall, there is some evidence of an association between exposure to indoor combustion and asthma, particularly asthma symptoms in children. Some sources of combustion such as coal stoves have been more consistently associated with these outcomes than other sources such as woodstoves.     

Validity of the Veterans Health Administration's traumatic brain injury screen

Belanger HG, Vanderploeg RD, Soble JR, Richardson M, Groer S. Validity of the Veterans Health Administration's traumatic brain injury screen.ObjectiveTo compare the results of Veterans Affairs' (VA's) initial traumatic brain injury (TBI) Clinical Reminder Screen with the more extensive second-level Comprehensive TBI Evaluation in a national sample.DesignCriterion-standard.SettingVeterans Health Administration system of polytrauma care.ParticipantsThe data were from VA's centralized database Patient Care Services on the TBI Clinical Reminder Screen and Comprehensive TBI Evaluation results of veterans (N=48,175).InterventionsNone.Main Outcome MeasuresSensitivity, specificity, positive predictive value, and negative predictive value of the TBI Clinical Reminder Screen were calculated by using the Comprehensive TBI Evaluation findings as the comparative standard for TBI confirmation.ResultsThe TBI Clinical Reminder Screen has generally good sensitivity (.87–.90) but poor specificity (.13–.18). In addition, the TBI Clinical Reminder Screen, when compared with the Comprehensive TBI Evaluation by a clinician, has generally poor negative predictive power (.31–.49) in this sample. However, negative predictive power is good with an estimated Veterans Health Administration system-wide TBI prevalence rate of 15% (.89). Positive predictive power was acceptable (.77) in this sample. The screen performs comparably across patient demographic and symptom severity characteristics, as well as across level of polytrauma care. Systematic evaluations by clinicians primarily reveal mental health–perceived causes of ongoing symptoms.ConclusionsIn summary, VA's Clinical Reminder Screen, when evaluated against the follow-up Comprehensive TBI Evaluation, has good sensitivity but poor specificity.     

Initial developmental process of a VA semistructured clinical interview for TBI identification

Identification of a remote traumatic brain injury (TBI), particularly mild TBI, is a challenge. The acknowledged standard for determining a history of prior TBI is self-report elicited through a structured or in-depth clinical interview. In April 2007, the Veterans Health Administration (VHA) mandated that the four-section TBI Clinical Reminder screening instrument be completed on all individuals returning from deployment in the Operation Iraqi Freedom/Operation Enduring Freedom theaters of operation (VHA Directive 2007-013). If positive, a follow-up Second Level TBI Evaluation is to be completed. For validation studies of the TBI Clinical Reminder screening process and with the long-term goal of providing a structured methodology to complete the TBI history portion of the Second Level TBI Evaluation, we sought to develop a "criterion standard" semistructured clinical TBI identification interview. This tool was developed through consultation with TBI subject matter experts and built on the strengths of existing tools in the literature. This article describes the six-step developmental methodology and presents the resulting semistructured interview and accompanying manual.     

Does a third party observer affect neuropsychological test performance? It depends

This study is a meta-analysis of available literature examining the effect of an observer on cognitive task performance. Of the 210 identified relevant articles, 62 met inclusion criteria yielding a final sample with 4405 individuals (2496 observed cases, 1909 not observed). The overall effect size was significant (d=-0.24), i.e., the presence of an observer was associated with poorer performance. However results were moderated by the effect size calculation method, cognitive domain, visibility of the observer, and number of observers. Attention, learning/memory, and delayed recall tasks were most adversely impacted by the presence of an observer.