Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33 % less likely to die from ALS compared to those inactive: HR = 0.67 (95 % CI 0.42-1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased-not increased like in case-control studies-risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity.Peer reviewe

Effects of polycyclic aromatic hydrocarbons on proliferation, collagen secretion and viability of arterial smooth muscle cells in culture

Previous reports have suggested a role for polycyclic aromatic hydrocarbons in the pathogenesis of atherosclerosis. Therefore, the effects of benzpyren (BP) and dimethylbenzanthracene (DMBA) on the arterial smooth muscle cell (SMC) in culture were studied. DMBA increased the proliferation of bovine and rabbit SMC but not of human embryonal fibroblasts or human SMC. BP did not significantly influence the cell number of bovine SMC. The secretion of newly synthesized collagen was always decreased when SMC were exposed to BP or DMBA. When BP or DMBA were added to SMC in plasma with high lipid levels compared to low levels, a decrease in total cellular DNA was seen together with a relatively higher collagen secretion. The same effects were noted when SMC had been preincubated with platelet factors compared to serum free medium, i.e. diminished cellular DNA and increased collagen secretion after BP or DMBA exposure. Cell death, measured as release of prelabelled 3H-thymidine from cell layers, was increased after exposure to BP 10 micrograms/ml while DMBA 0.05-0.1 microgram/ml led to a significantly lesser cell death compared to controls in serum free media. It was also shown that SMC exposed to DMBA might release mitogenic factors to conditioned media. It is concluded that, depending on the mode of administration, the polycyclic aromatic hydrocarbons BP and DMBA may induce different effects on arterial SMC in vitro as increased or decreased toxicity and collagen secretion, and increased proliferation and that these effects might be of importance in the pathogenesis of atherosclerosis

Differences in cardiac disease prevalence and in blood variables between major and minor stroke patients

In 310 patients with carotid territory stroke, we investigated whether a history of cardiac disease was more frequent among those with major stroke (n = 169) than among those with minor stroke (n = 141), and whether the two groups differed in values for blood variables directly or indirectly associated with stroke, each variable being adjusted for age and sex. A history of angina pectoris was more frequent in the major stroke than in the minor stroke group, 16% vs. 9% (p < 0.042; odds ratio, 2.2); and among female patients, a history of atrial fibrillation was more common in those with major stroke than in those with minor stroke, 35% vs. 13% (p < 0.033; odds ratio, 2.8). ESR (erythrocyte sedimentation rate) values were higher in the major than in the minor stroke group, 21 +/- 21 (mean +/- SD) vs. 15 +/- 14 mm/h (p < 0.028), as were WBC (white blood cell) counts, 9.4 +/- 3.2 vs. 7.9 +/- 2.3 x 109/l, p < 0.001. WBC counts were also higher in stroke survivors than in non-survivors, 9.6 +/- 3 vs. 8.3 +/- 3 x 109/l (p < 0.0027), as were serum creatinine values, 115 +/- 59 vs. 95 +/- 21 mumol/l (p < 0.0094). The differences between major and minor stroke patients may reflect differences in the degree of atherosclerosis and thrombogenicity

Interactions between cultured bovine arterial endothelial and smooth muscle cells; further studies on the effects of injury and modification of the consequences of injury

The hypothesis that cells of the arterial wall might modify the consequences of arterial injury was tested. Bovine aortic endothelial cells (EC) or smooth muscle cells (SMC) were exposed to the two toxic stimuli 3,4-benzo(a)pyrene (BP) and dimethylsulfoxide-soluble particulate matter from cigarette smoke (DSP) or factors released from platelets. The modification of the injury caused by these substances on arterial cells was studied by using a conditioned medium from arterial cells or an EC-SMC co-culture model. Direct addition of BP or DSP to the EC or SMC cultures induced toxic effects on the cells. DSP caused a decreased release of prostacyclin by EC. Conditioned medium from EC and SMC modified these toxic effects, which resulted in a reduced cell death and a further decreased cell proliferation, while conditioned medium from SMC increased the release of prostacyclin by EC injured by DSP. In EC-SMC co-culture the same modifications were obtained. The modification of cell injury was not linked to cell proliferation but instead the results suggested that the effects were mediated by multiple substances released from arterial cells. It is concluded that interactions between different cells in the arterial wall, in the non-injured as well as in the injured state, could be modified by endogeneous substances. This might be of relevance for atherogenesis

Interactions between cultured bovine arterial endothelial and smooth muscle cells : effects of injury on the release of growth stimulating and growth inhibiting substances

Dimethylsulfoxide-soluble particles (DSP) from cigarette smoke and ultraviolet light caused a low degree (cell death less than 30%) and high degree (cell death 60-90%) injury to bovine arterial endothelial cells and smooth muscle cells in culture. Conditioned medium from low degree injured endothelial cells and smooth muscle cells generally inhibited DNA synthesis in new smooth muscle cells or endothelial cells while high degree injury increased DNA synthesis in new cells. Specifically, the growth stimulating activity from endothelial cells was decreased after low degree injury but increased after high degree. UV light released more growth stimulating substances from smooth muscle cells after both low and high degree injury. The release of growth inhibiting substances was dependent on both cell kind and degree of injury. In co-culture low and high degree DSP injury to endothelial cells inhibited smooth muscle cell proliferation, which was in contrast to the effect of conditioned medium from high degree injured endothelial cells. Conditioned medium from endothelial cells treated with LDL and glucose inhibited DNA synthesis in smooth muscle cells. It is concluded that injury to endothelial cells or smooth muscle cells will modify the release of growth inhibiting and growth stimulating activity and that this release will depend on cell kind as well as degree and kind of the injurious stimulus

Interactions between cultured bovine arterial endothelial and smooth muscle cells; studies on the release of prostacyclin by endothelial cells

The release of prostacyclin by endothelial cells (EC) in culture was studied after exposure to two toxic stimuli (UV light or dimethylsulfoxide-soluble smoke particles (DSP)) or to medium conditioned by smooth muscle cells (SMC), basically or after injury to the SMC. An activity stimulating the release of prostacyclin was found together with growth inhibiting activity from arterial SMC, but dissociated from growth stimulating activity. The prostacyclin stimulating activity was increased when SMC were exposed to UV light, while DSP caused a decrease. EC directly exposed to UV light or DSP generally released more prostacyclin than controls. One exception was very low concentrations of DSP. UV light induced a burst of release in contrast to DSP where a continuous release after a two hours lag period was seen. It is concluded that EC will increase the release of prostacyclin in response to injury but the release pattern will depend on the kind and doses of the stimulus. SMC release prostacyclin stimulating activity for EC, which can be modified by exposure to toxic stimuli. The results might have applications for atherogenesis

Interactions between cultured bovine arterial endothelial and smooth muscle cells; effects of modulated low density lipoproteins on cell proliferation and prostacyclin release

We exposed bovine aortic endothelial cells in culture to native LDL (n-LDL) and LDL modulated by dimethylsulfoxide (DMSO-LDL), dimethylsulfoxide-soluble particles from cigarette smoke (DSP-LDL) or Cu2+ (Cu(2+)-LDL) to explore the hypothesis that these LDL-forms might influence interactions between endothelial and smooth muscle cells. It was shown that 3H-thymidine incorporation into endothelial cells was decreased by DMSO-LDL, DSP-LDL and Cu(2+)-LDL compared to n-LDL, while it was higher by DSP-LDL compared to its control i.e. DMSO-LDL. These effects could be transferred by conditioned medium to smooth muscle cell cultures. DSP-LDL or Cu(2+)-LDL decreased total cellular protein of endothelial cells. Initial (15 min) prostacyclin release from endothelial cells was increased by all LDL preparations compared to medium without LDL, most pronounced for Cu(2+)-LDL. If n-LDL was control, only Cu(2+)-LDL significantly increased the release of prostacyclin during 15 min and during 24 h. The release of prostacyclin assayed after 24 h was depressed by DSP-LDL compared to DMSO-LDL. This study demonstrated that interactions between endothelial and smooth muscle cells could be influenced by LDL treated by dimethylsulfoxide-soluble particles from cigarette smoke or by Cu2+, and their effects were not similar. DSP-LDL, in contrast to Cu(2+)-LDL, significantly decreased the release of prostacyclin by endothelial cells after 24 h incubations and via endothelial cell conditioned medium stimulated smooth muscle cell proliferation judged by increased 3H-thymidine incorporation. The results might be of relevance for atherogenesis

Patient Participation and the Environment : A Scoping Review of Instruments

Patient participation and the environment are critical factors in achieving qualitative healthcare. We conducted a systematic scoping review using Arksey and O’Malley’s framework to identify instruments intended to measure patient participation. We assessed those instruments’ characteristics, which areas of the healthcare continuum they target, and whether environmental factors are considered. Instruments were considered eligible if they represented the patient perspective and measured patient participation in healthcare. The search was limited to articles written in English and published in the last 10 years. We extracted concepts (i.e., patient empowerment, patient participation, and patient-centeredness) based on the framework developed by Castro et al. and outcomes of significance regarding the review questions and specific objectives. The search was conducted in PsycINFO, CINHAL/EBSCO, and PubMed in September 2019 and July 2020. Of 4802 potential titles, 67 studies reported on a total of 45 instruments that met the inclusion criteria for this review. The concept of patient participation was represented most often in these studies. Although some considered the social environment, no instrument was found to incorporate and address the physical environment. Thirteen instruments were generic and the remaining instruments were intended for specific diagnoses or healthcare contexts. Our work is the first to study instruments from this perspective, and we conclude that there is a lack of instruments that measure aspects of the social and physical environment coherently as part of patient participation. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Increased smooth muscle cell proliferation by dimethylbenzanthracene is correlated to variations in activity of ornithine decarboxylase but not arylhydrocarbonhydroxylase

Polycyclic aromatic hydrocarbons of cigarette smoke have been suggested to be involved in atherogenesis. After being converted to epoxides by monooxidases in the arterial wall the hydrocarbons may exert toxic or mutagenic effects on the smooth muscle cells (SMC). In a previous study we found that dimethylbenzanthracene (DMBA), an inducer of arylhydrocarbonhydroxylase (AHH), increased SMC proliferation and viability. In the present work we intended to study whether these effects were mediated by AHH. Alpha-naphtoflavone (ANF), a non specific AHH inhibitor, decreased SMC proliferation. The effects of ANF were totally counteracted by serum, partially by albumin and not at all by platelet derived growth factor. AHH activity was not detectable nor basally nor after induction in SMC, and this made us conclude that the effects of DMBA and ANF on SMC proliferation were not mediated by AHH. On the other hand the activity of ornithine decarboxylase was influenced by DMBA and ANF in parallel to proliferation, suggesting the involvement of this enzyme in the described DMBA effects on SMC proliferation. This mechanism might be of relevance for the pathogenesis of atherosclerosis especially in relation to cigarette smoking