Exercise training improves long-term memory in obese mice

Obesity has been linked to a range of pathologies, including dementia. In contrast, regular physical activity is associated with the prevention or reduced progression of neurodegeneration. Specifically, physical activity can improve memory and spatial cognition, reduce age-related cognitive decline, and preserve brain volume, but the mechanisms are not fully understood. Accordingly, we investigated whether any detrimental effects of high-fat diet (HFD)-induced obesity on cognition, motor behavior, adult hippocampal neurogenesis, and brain-derived neurotrophic factor (BDNF) could be mitigated by voluntary exercise training in male C57Bl/6 mice. HFD-induced impairment of motor function was not reversed by exercise. Importantly, voluntary wheel running improved long-term memory and increased hippocampal neurogenesis, suggesting that regular physical activity may prevent cognitive decline in obesity

Visual Experiences during Paralysis

Rationale: Paralyzed human volunteers (n = 6) participated in several studies the primary one of which required full neuromuscular paralysis while awake. After the primary experiment, while still paralyzed and awake, subjects undertook studies of humor and of attempted eye-movement. The attempted eye-movements tested a central, intentional component to one’s internal visual model and are the subject of this report. Methods: Subjects reclined in a supportive chair and were ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination, subjects were requested to focus alternately on the faces of investigators standing on the left and the right within peripheral vision. In darkness, subjects were instructed to look away from a point source of light. Subjects were to report their experiences after reversal of paralysis. Results: During attempted eye-movement in illumination, one subject had an illusion of environmental movement but four subjects perceived faces as clearly as if they were in central vision. In darkness, four subjects reported movement of the target light in the direction of attempted eye-movements and three could control the movement of the light at will. Conclusion: The hypothesis that internal visual models receive intended ocular-movement-information directly from oculomotor centers is strengthened by this evidence

Visual Experiences during Paralysis

Rationale: Paralyzed human volunteers (n = 6) participated in several studies the primary one of which required full neuromuscular paralysis while awake. After the primary experiment, while still paralyzed and awake, subjects undertook studies of humor and of attempted eye-movement. The attempted eye-movements tested a central, intentional component to one’s internal visual model and are the subject of this report. Methods: Subjects reclined in a supportive chair and were ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination, subjects were requested to focus alternately on the faces of investigators standing on the left and the right within peripheral vision. In darkness, subjects were instructed to look away from a point source of light. Subjects were to report their experiences after reversal of paralysis. Results: During attempted eye-movement in illumination, one subject had an illusion of environmental movement but four subjects perceived faces as clearly as if they were in central vision. In darkness, four subjects reported movement of the target light in the direction of attempted eye-movements and three could control the movement of the light at will. Conclusion: The hypothesis that internal visual models receive intended ocular-movement-information directly from oculomotor centers is strengthened by this evidence

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Receptor-mediated phosphoinositide metabolism in the rat cerebellar granule cell.

Cerebellar granule cells in culture have recently become a widely used neuronal preparation, because of their receptor integrity and ability to release the neurotransmitter, glutamate. The basis of this thesis was the detailed investigation of receptor-mediated phosphoinositide signalling and its role in intracellular Ca2+ in this cell type. The muscarinic activated accumulation of 3H-InsPx in this cell is the most potent reported, stimulating some 20 fold over basal and was selected as the agonist of choice for further study. Pharmacological determination of antagonist inhibition of 3H-NMS binding and 3H-InsPx production, identified the muscarinic receptor coupled to PI hydrolysis as of the M3 receptor subtype. Carbachol induced 3H-InsPx was demonstrated, at least in part, to originate from the hydrolysis of PtdInsP2, due to the capacity of the cell to produce Ins(1,4,5)P3, the intracellular Ca2+-mobilising second-messenger. The calcium mobilising properties now well established for Ins(1,4,5)P3, were confirmed in the cerebellar granule cell. 45Ca2+ release by Ins(1,4,5)P3 was stereospecific, heparin sensitive. Displacement of 32P-Ins(1,4,5)P3 confirmed the presence of Ins(1,4,5)P3 sites, that had previously gone undetected in this cell type. Fluorescent Ca2+ indicators, like fura-2, have recently been developed and enable the detailed analysis of intracellular [Ca2+] changes to be performed in intact cells, both in population and at the single cell level. Single cell studies in fura-2 loaded cerebellar granule cells, showed considerable heterogeneity in their responsiveness to carbachol. Very few cells demonstrated a classical receptor mediated Ins(1,4,5)P3-type increase in [Ca2+]i, the majority being dependent on extracellular Ca2+. Most cells exhibited a muscarinic-mediated Ca2+ entry phenomenon, that was only visible in the absence of extracellular Mg2+, suggesting some added complexity that needs further investigation. The possibility of a role of Ins(1,4,5)P3 in neurotransmitter release in this cell type is considered

Predicting prolonged dysphagia in acute stroke: The Royal Adelaide Prognostic Index for Dysphagic Stroke (RAPIDS)

The original publication can be found at www.springerlink.comDysphagia is common after stroke and is associated with increased morbidity and mortality. Predicting those who are likely to have significant prolonged dysphagia is not possible at present. This study was undertaken to validate the Royal Adelaide Prognostic Index for Dysphagic Stroke (RAPIDS) in the prediction of prolonged dysphagia following acute stroke using clinical and radiographic features. A prospective study of unselected, consecutive admissions to the Royal Adelaide Hospital acute stroke unit was undertaken. Clinical and radiographic features applicable to the RAPIDS test were calculated and the sensitivity, specificity, and likelihood ratio for predicting prolonged dysphagia were calculated with 95% confidence intervals (CI). Of 104 subjects admitted with acute stroke, 55 (53%) had dysphagia and 20 (19%) had dysphagia requiring nonoral feeding/hydration for 14 days or more or died while dysphagic prior to 14 days. The RAPIDS test had sensitivity of 90% (95% CI = 70–97%) and specificity of 92% (95% CI - 84–96%) for predicting this latter group of patients. We conclude that the RAPIDS test can be used early to identify patients likely to have prolonged dysphagia. This test could form a basis for selection of patients for trials of nonoral feeding methods.Simon Broadley, Alison Cheek, Susie Salonikis, Emma Whitham, Victoria Chong, David Cardone, Basile Alexander, James Taylor and Philip Thompso