Perceptions of people with intellectual and developmental disabilities about COVID-19 in Spain: a cross-sectional study.

BACKGROUND: As the world battles COVID-19, there is a need to study the perceptions of people with intellectual and developmental disabilities (IDD) about the effects of the pandemic and associated lockdown on their lives. This work explores the perceptions of Spaniards with IDD during the lockdown with respect to four topics: access to information, emotional experiences, effects on living conditions and access to support. METHODS: The topics were explored using a subset of 16 closed-ended questions from an online survey. In total, 582 participants with IDD completed the survey. The frequencies and percentages of responses to the questions were calculated, and chi-square tests performed to explore the relationship between participants' sociodemographic characteristics and responses. Given that people differed in the way in which they completed the survey, the relationship between participants' responses and completion method was also analysed. RESULTS: Participants reported that the pandemic and subsequent lockdown have had a deleterious effect on their emotional well-being (around 60.0% of participants) and occupations (48.0% of students and 72.7% of workers). Although access to information and support was reportedly good overall, being under the age of 21 years and studying were associated with perceptions reflecting poorer access to information (V = .20 and V = .13, respectively) and well-being support (V = .15 and V = .13, respectively). Being supported by a third party to complete the survey was consistently related to perceptions of worse outcomes. CONCLUSIONS: The study yielded data on the perceptions of people with IDD regarding the effects that COVID-19 and the subsequent lockdown have had on their lives. Suggestions on how to overcome the difficulties reported and future lines of research are discussed.

Assessing support needs in children with intellectual disability and motor impairments: measurement invariance and group differences.

BACKGROUND: This study assessed the equivalence of the measurement of support needs between children with intellectual disability (ID) and children with intellectual and motor disabilities (IMD) and compared both groups in the different domains of support. METHOD: The Supports Intensity Scale-Children's Version was used to assess the support needs of 713 children with ID and 286 children with IMD, mainly associated with cerebral palsy. RESULTS: The results supported measurement invariance between the group of ID and IMD, which allowed to conduct comparison between them. Children with IMD scored higher on support needs than did children without IMD, suggesting that children with IMD needed more support than their peers without motor impairments. Furthermore, the ID levels interacted with motor impairments: at the highest levels of ID, groups tended to be similar in support needs, with high scores and low variability. The greatest differences were found in the domains of Home and Community activities. CONCLUSIONS: This study points to the across-condition of the construct of support needs in populations with intellectual and developmental disabilities. However, additional mobility impairments should be considered during the evaluation and planning of systems of support. In this regard, the Supports Intensity Scale-Children's Version might have limitations when discriminating between samples with high support needs.

Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D003, a mixture of very long-chain saturated fatty acids.

Previous results have demonstrated that policosanol, a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, whose main component is octacosanol, inhibited lipid peroxidation in experimental models and human beings. D003 is a defined mixture of very long-chain saturated fatty acids, also isolated and purified from sugar cane wax, whose main component is octacosanoic acid followed by traicontanoic, dotriacontanoic, and tetracontanoic acids. Since very long-chain fatty acids are structurally related to their corresponding alcohols, we investigated the effect of oral treatment with D003 (0.5, 5, 50, and 100 mg/kg) over 4 weeks in reducing the susceptibility of rat lipoprotein to oxidative modification. The combined rat lipoprotein fraction VLDL + LDL was subjected to several oxidation systems, including those containing metal ions (CuSO4), those having the capacity to generate free radicals 2,2-azobis-2-amidinopropane hydrochloride (AAPH), and a more physiological system (resident macrophages). D003 (5, 50, and 100 mg/kg) significantly inhibited copper-mediated conjugated-diene generation in a concentration-dependent manner. D003 increased lag phase by 53.1, 115.3, and 119.3%, respectively, and decreased the rate of conjugate-diene generation by 16.6, 21.5, and 19.6%, respectively. D003 also inhibited azo-compound initiated and macrophage-mediated lipid peroxidation as judged by the significant decrease in thiobarbituric acid reactive substance (TBARS) generation. In all the systems the maximum effect was attained at 50 mg/kg. There was also a parallel attenuation in the reduction of lysine amino groups and a significant reduction of carbonyl content after oxidation of lipoprotein samples. Taken together, the present results indicate that oral administration of D003 protects lipoprotein fractions against lipid peroxidation in the lipid as well in the protein moiety.

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids.

The present study was undertaken to investigate the effects of D003, a mixture of very long chain saturated fatty acids isolated and purified from sugar cane wax, on cholesterol biosynthesis in cultured fibroblasts. Cholesterol biosynthesis is regulated through feedback regulation of at least two sequentially acting enzymes, 3-hydroxy-3-methyl coenzyme A (HMG-CoA) synthase and reductase. They are up-regulated when sterol levels fall and down-regulated when sterol levels rise. The exposure of cultured fibroblasts to a lipid-depleted medium (LDM) and D003 (0.05-50 microg ml(-1)) for 12 h inhibited, in a dose-dependent manner, cholesterol biosynthesis from 14C-labelled acetate (33-68%). The addition of D003 at concentrations inhibiting cholesterol biosynthesis from labelled acetate significantly decreased incorporation of radioactivity from 3H2O into sterols, but not from 14C-mevalonate. These data indicate that D003 inhibits cholesterol biosynthesis by interfering with early steps of cholesterol biosynthetic pathway. We reasoned that D003 acts directly on HMG-CoA reductase, the main regulatory enzyme of cholesterol biosynthetic pathway. However, when enzyme activity was measured in cell extracts in the presence of various concentrations of D003 (0.5-50 microg ml(-1)), reductase activity was not inhibited. Thus, there was no evidence for a competitive or non-competitive inhibition of enzyme activity by D003. Treatment with D003 significantly suppressed (68%) the enzyme up-regulation when cells were cultured in LDM, which suggests a depression of de novo synthesis of HMG-CoA reductase and/or a stimulation of its degradation. However, since the suppressive action of D003 on cholesterol biosynthesis was observed in metabolic conditions under which synthase up-regulation was also enhanced, we cannot rule out a possible effect of D003 on HMG-CoA synthase. Thus, further studies are needed to clarify the precise mechanism of the inhibitory effect of D003 on cholesterol biosynthesis.

Antioxidant effects of D002 on the in vitro susceptibility of whole plasma in healthy volunteers.

BACKGROUND: It has been recently shown that oral administration of D002, a mixture of higher aliphatic primary alcohols isolated from beeswax, inhibits rat microsomal lipid peroxidation. This justified the present attempt to investigate whether D002 also exerts antioxidant effects in humans. METHODS: The effects of D002 on lipid peroxidation were studied in a double-blind, randomized, placebo-controlled trial conducted in 50 healthy volunteers. Unfractionated plasma samples at baseline and at 12 weeks were subjected to in vitro copper-induced lipid peroxidation and conjugated diene generation was monitored by changes of optical density. RESULTS: The oral treatment with D002 (50 mg/day) not only significantly prolonged (p <0.001) lag time before the onset of conjugated diene formation compared with that of baseline but also increased (p <0.05) lag phase when compared with placebo group. In fact, in the D002 group the lag-phase of oxidation was prolonged 1.5-fold. D002 oral treatment decreased TBARS and increased plasma total antioxidant status (TAS) (p <0.01). CONCLUSIONS: Because prooxidant states have been linked to normal senescence and some age-related diseases, the present data suggest that D002 may find a use in preventing age-related diseases as a dietary natural antioxidant supplement.

Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts.

BACKGROUND: Cholesterol biosynthesis is strictly controlled by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. METHODS: Transfer of cultured fibroblasts to a lipid-depleted medium (LDM) up-regulates the enzyme levels. This, in turn, is followed by an accelerated biosynthesis of cholesterol. RESULTS: Exposure of Vero fibroblasts to LDM and policosanol (0.5-50 microg/mL), a new cholesterol-lowering drug purified from sugarcane (Saccharum officinarum L.) wax, decreased in a dose-dependent manner cholesterol biosynthesis from [14C]-acetate and 3H-water, but not from [14C]-mevalonate. CONCLUSIONS: This suggests an effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis. When enzyme activity was measured in the presence of various concentrations of policosanol (0.5-50 microg/mL), reductase was not suppressed. Therefore, there was no evidence for a competitive or noncompetitive inhibition of enzyme activity. However, after treatment of intact cells with policosanol (50 microg/mL) in the presence of LDM, a suppressive effect on enzyme activity was observed, suggesting a modulatory effect of policosanol on reductase activity. The previous inhibition of enzyme up-regulation by policosanol suggests to date a depression of de novo synthesis of HMG-CoA reductase and/or stimulation of its degradation. However, the exact mechanism by which policosanol inhibits the activity of HMG-CoA reductase still remains unclear. Further studies are needed to clarify the precise mechanism of its inhibitory action on cholesterol biosynthesis.

Effects of D-002 on Lipid Peroxidation in Older Subjects.

D-002 is a mixture of higher aliphatic alcohols isolated from beeswax that inhibits rat microsomal lipid peroxidation in vitro and in vivo. This study was undertaken to investigate whether D-002 also inhibits lipid peroxidation in older subjects. The free radical theory of aging suggests that progressive defects in the protection against free radical reactions leads to progressive deleterious effects of free radicals on cells and tissues. This free radical damage has been implicated in several pathophysiological processes associated with the chronic degenerative diseases that occur with aging. Forty-eight older subjects were randomly assigned, in a double-blind fashion, to receive placebo or D-002 tablets (50 mg/day) once daily. At baseline, D-002 and placebo groups were well matched regarding several variables. D-002 significantly reduced the susceptibility of nonfractionated plasma samples to copper-mediated lipid peroxidation. It also significantly increased the length of the lag phase (P <.001) and the total antiioxidant status (P <.05) compared with baseline and placebo. In addition, D-002 significantly decreased malondialdehyde levels (expressed in terms of thiobarbituric acid reactive substances (TBARS, P <.001) compared with baseline, but not with placebo. No significant changes on lipid peroxidation parameters were observed in the placebo group. We conclude that D-002 treatment may be useful to prevent or manage certain pathophysiological conditions in the elderly.

Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro.

AIMS: The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. METHODS: The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation. RESULTS: At baseline all groups were well matched regarding all variables. After 8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in a dose-dependent manner increased the lag phase of conjugated diene generation (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from 8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found. CONCLUSIONS: The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002.

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46%) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40%) and brain (28-44%) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46 percent) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40 percent) and brain (28-44 percent) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans

Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation.

Policosanol, a new cholesterol-lowering agent, is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) wax, which prevents the onset of espontaneously and experimentally induced atherosclerotic lesions in experimental models. Because the oxidation of low-density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis, we investigate the effect of policosanol on copper oxidative susceptibility of rat lipoprotein fractions (VLDL + LDL). Rats fed normal diet were treated with policosanol (250-500 mg/kg/day) for up to 4 weeks. EDTA-free lipoprotein particles were oxidized in a cell-free system by the addition of copper ions, and conjugated dienes generation was monitored by changes of optical density at 234 nm. Thiobarbituric acid-reactive substances (TBARS) content and lysine-amino group reactivity were investigated. After administration, there was no change in cholesterol, triglycerides, and phospholipid content of lipoprotein fractions; however, policosanol significantly prolongs the lag time and reduces the propagation rate of diene generation. Also, policosanol reduces TBARS content and increases lysine reactivity in lipoprotein fractions treated with Cu2+. In conclusion, policosanol, in addition to its cholesterol-lowering effect, has other properties that enables it to reduce the potential of lipoprotein to undergo lipid peroxidation. Such effect can be considered of promissory value in the management of atherosclerosis.

Effect of policosanol on in vitro and in vivo rat liver microsomal lipid peroxidation.

Policosanol, a defined mixture of high molecular weight aliphatic alcohol isolated and purified from sugar cane (Saccharum officinarum, L) wax is a new cholesterol-lowering agent effective in experimental models, healthy volunteers, and patients with type II hypercholesterolemia. Also, policosanol prevents the onset of spontaneously- and experimentally-induced atherosclerotic lesions and cerebral ischemia in Mongolian gerbils. Free radicals are linked to many diseases including atherosclerosis and ischemia/ reoxidation cellular injury. Therefore, in this study the authors evaluate the antioxidant activity of policosanol on rat liver microsomes. The extent of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS). When policosanol was administered orally (100 and 250 mg/kg) for up to 4 weeks, a partial prevention of rat in vitro microsomal lipid peroxidation was noted. The formation of TBARS in microsomes isolated from treated rats was significantly decreased by about 50%, when peroxidation was initiated by Fe3+/ADP/ NADPH, Fe2+/ascorbate and CCl4/NADPH-generating system. Also, oral administration of policosanol in rats provides a partial inhibition of lipid peroxidation, but the mechanism supporting such effect remains to be elucidated. This beneficial effect of policosanol on membrane lipid peroxidation may be useful in protecting to some extent against free radical-associated diseases.

Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet.

The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugarcane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50 mg/kg) the increases in plasma total cholesterol and LDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125I-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t1/2) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.

Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats.

We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorporation of 3H-water in sterols were depressed by policosanol by about 20%, giving a more accurate degree of cholesterol biosynthesis inhibition in this species. Since policosanol did not inhibit labeled mevalonate incorporation into cholesterol in rat liver, we also studied the effect of policosanol on hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in microsomes treated with policosanol remained unchanged, suggesting that cholesterol synthesis is not inhibited by a direct action of policosanol on this enzyme.

Characterization of a potassium channel toxin from the Caribbean Sea anemone Stichodactyla helianthus.

A peptide toxin, ShK, that blocks voltage-dependent potassium channels was isolated from the whole body extract of the Caribbean sea anemone Stichodactyla helianthus. It competes with dendrotoxin I and alpha-dendrotoxin for binding to synaptosomal membranes of rat brain, facilities acetylcholine release at an avian neuromuscular junction and suppresses K+ currents in rat dorsal root ganglion neurones in culture. Its amino acid sequence is R1SCIDTIPKS10RCTAFQCKHS20MKYRLSFCRK30TCGTC35. There is no homology with other K+ channel-blocking peptides, except for BgK from the sea anemone Bunodosoma granulifera. ShK and BgK appear to be in a different structural class from other toxins affecting K+ channels.

Effects of policosanol chronically administered in male monkeys (Macaca arctoides).

Policosanol, administered orally, has shown a cholesterol-lowering effect in different experimental models. Because lipid-lowering therapy is administered chronically, it is necessary to know the effects of these drugs after long-term administration. 18 adult male Macaca arctoides monkeys were used to study the cholesterol-lowering effects and possible toxicity produced by oral administration of policosanol (0.25, 2.5 and 25 mg/kg) for 54 wk. After 8 wk, a significant reduction of serum total cholesterol and low-density lipoprotein cholesterol was observed in policosanol-treated animals when compared with the controls; this effect persisted throughout the study. The animals' behavioural repertoire, physical condition, haematology and blood biochemistry, as well as spermiogram analysis and electrocardiography, were monitored during the study; ophthalmological and pathological anatomy examinations were performed at the end of the administration period. No drug-related toxicity was detected by any examination. The results gave further evidence of the marked and persistent cholesterol-lowering effects of policosanol that had been observed in different experimental models. There was a significant reduction of spontaneous aortic atherosclerotic lesions in treated animals compared with controls. Policosanol (0.25-25 mg/kg) administered orally for 54 wk brought about a persistent reduction in blood cholesterol levels and was very safe and well tolerated during long-term administration.

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts.

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity.

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity