Making the (Business) Case for Clinical Ethics Support in the UK

HEC Forum - This paper provides a series of reflections on making the case to senior leaders for the introduction of clinical ethics support services within a UK hospital Trust at a time when...     

Older gay men's engagement with physical activity: A scoping review

Older gay men experience an elevated prevalence of adverse health conditions that may be compounded by age-related deterioration. Some of these conditions may be ameliorated by regular adherence to physical activity (PA). However, many gay men participate in less PA than their age-matched heterosexual counterparts. With a focus on gay men aged 60 and over, the aims of this review were to examine the evidence for older gay men's engagement with PA and the research approaches used to describe this group. A systematic search of six academic databases (Academic Search Premier, Cinahl, PubMed, Sport Discus, APA PsychInfo and APA PsychArticles) generated 23 papers from 1970 to 2020 that focused on older gay men's engagement with PA. Although surveys were well represented in the literature, further studies utilising qualitative methodological frameworks have the potential to inform targeted interventional programs aimed at reducing less health disparities. The value of PA in older adults lies principally in improved performance of activities of daily living, independent living, increased longevity, decreased cognitive decline and improved mental well-being.     

M-Cell Surface β1 Integrin Expression and Invasin-Mediated Targeting of Yersinia pseudotuberculosis to Mouse Peyer’s Patch M Cells

Quantitative analysis of Yersinia pseudotuberculosis infection of murine gut loops revealed that significantly more wild-type bacteria associated with Peyer’s patch M cells than with dome enterocytes or goblet cells. An invasin-deficient mutant was significantly attenuated for M-cell invasion, while β1 integrin expression was demonstrated in the apical membranes of M cells but not enterocytes. M-cell targeting by Yersinia pseudotuberculosis in vivo may, therefore, be mediated primarily by the interaction of invasin with cell surface β1 integrins.     

Integration of multiple sensory modalities in cat cortex

Summary The results of this study show that the different receptive fields of multisensory neurons in the cortex of the cat anterior ectosylvian sulcus (AES) were in spatial register, and it is this register that determined the manner in which these neurons integrated multiple sensory stimuli. The functional properties of multisensory neurons in AES cortex bore fundamental similarities to those in other cortical and subcortical structures. These constancies in the principles of multisensory integration are likely to provide a basis for spatial coherence in information processing throughout the nervous system.     

Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey

The reduction in symptoms of Parkinson's disease produced by high-frequency stimulation (HFS) in the internal globus pallidus (GPi) has been proposed to be due to stimulus-induced inactivation of pallidal neurons and resulting disinhibition of thalamic neurons. We tested this in awake Macaca fascicularis by stimulating between pairs of electrodes inserted into GPi under electrophysiological control and recording the responses evoked in thalamic neurons. HFS produced a reduction, not an increase, in discharge frequency during the stimulus train in 77% of the responsive thalamic neurons. Only 16% of the responsive cells showed an increase in discharge during stimulation and, for some of these, stimulation at a similar intensity produced contralateral muscle contraction, a probable sign of current spread to the internal capsule. The few thalamic neurons studied during bursting had a reduction in burst frequency and duration during HFS. We conclude that high-frequency stimulation within GPi does not necessarily facilitate thalamic discharge, and it may act, instead, to interrupt abnormal patterns of thalamic discharge associated with parkinsonian symptoms.     

Fugetaxis: active movement of leukocytes away from a chemokinetic agent

Chemotaxis or active movement of leukocytes toward a stimulus has been shown to occur in response to chemokinetic agents including members of the recently identified superfamily of proteins called chemokines. Leukocyte chemotaxis is thought to play a central role in a wide range of physiological and pathological processes including the homing of immune cells to lymph nodes and the accumulation of these cells at sites of tissue injury and pathogen or antigen challenge. We have recently identified a novel biological mechanism, which we term fugetaxis (fugere, to flee from; taxis, movement) or chemorepulsion, which describes the active movement of leukocytes away from chemokinetic agents including the chemokine, stromal cell derived factor-1, and the HIV-1 envelope protein, gp120. In this article, we review the evidence that supports the observation that leukocyte fugetaxis occurs in vitro and in vivo and suggestions that this novel mechanism can be exploited to modulate the immune response. We propose that leukocyte fugetaxis plays a critical role in both physiological and pathological processes in which leukocytes are either excluded or actively repelled from specific sites in vivo including thymic emigration, the establishment of immune privileged sites and immune evasion by viruses and cancer. We believe that current data support the thesis that a greater understanding of leukocyte fugetaxis will lead to the development of novel therapeutic approaches for a wide range of human diseases.     

Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries

 Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85±18 pA (n = 11), 148±22 pA (n = 11), and 193±29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4±0.5 nM, 6.1±1.1 nM, and 8.2±1.3 nM, respectively. Neither LOS (1 μM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77±6% inhibition with LOS (n = 8) and 63±9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release. Received: 24 September 1997 / Accepted: 20 October 1997