Motor skill competence and moderate- and vigorous-intensity physical activity: a linear and non-linear cross-sectional analysis of eight pooled trials.

BACKGROUND: Few studies have examined the relationship between motor skill competence and device-measured physical activity in large samples and none have used non-linear modelling. This study assessed the linear and non-linear associations between motor skill competence and physical activity in children using pooled data from eight studies. METHODS: Cross-sectional ActiGraph accelerometer and motor skills competence data from 988 children (50.8% boys) aged 3-11 years were included. Total, object control and locomotor skill competence were assessed using the Test of Gross Motor Skill Development. Linear mixed models were fitted to examine linear associations between motor skill competence and physical activity. Then, restricted cubic splines models were used to assess potential non-linear relationships. Interactions by sex and age were assessed. RESULTS: There was evidence of positive linear associations between total skill, and object control and locomotor skills, with moderate- and vigorous-intensity physical activity; however, the associations with total skill competence and object control better fitted a non-linear model. Non-linear models indicated associations were positive but relatively weak in the low to mid ranges of TGMD/object control scores but at high ranges (~ > 70 out of 100/ and ~ 35 out of 50) the association strength increased for both moderate- and vigorous-intensity physical activity. There were sex interactions for locomotor skills only, specifically for vigorous activity with boys having a stronger positive association than girls. CONCLUSIONS: There appears to be a threshold for object control skill proficiency that children need to reach to enhance their physical activity levels which provides support for a motor skill "proficiency barrier". This provides a tangible benchmark for children to achieve in motor competence programs.

How Do Physical Activity and Sedentary Behaviour Affect Motor Competence in Children with Autism Spectrum Disorder Compared to Typically Developing Children: A Pilot Study.

Older children with Autism Spectrum Disorder (ASD) have high levels of motor impairment, however we are unsure if similar patterns exist in young children. This study aimed to investigate motor competence in four-to-seven-year-old children with (n = 17) and without (n = 17) ASD. A series of ANOVAS indicated children with ASD performed significantly poorer on all measures of motor competence, except MABC-2 manual dexterity and ball skills subscales. Results indicate that moderate-to-vigorous physical activity (PA) and sedentary behaviour (SB) may influence motor competence, regardless of diagnosis. Establishing appropriate levels of engagement in moderate-to-vigorous PA and SB during early school years is important for the development of all children and may be an important early intervention avenue for motor impairment in children with ASD.

Molecular analysis of surface glycoprotein multigene family TrGP expressed on the plasma membrane of Trypanosoma rangeli epimastigotes forms.

Trypanosoma rangeli, a non-pathogenic hemoflagelate that in Central and South America infects humans, shares with Trypanosoma cruzi reservoirs and triatomine vectors, as well as geographical distribution. Recently, we have described in T. rangeli a truncated gene copy belonging to the group II of the trans-sialidase superfamily (TrGP). This superfamily, collectively known in T. cruzi as gp85/TS, includes members that are involved in host cell invasion and infectivity. To confirm the presence of this superfamily in the genome of T. rangeli and obtain a better knowledge of its characteristics, we designed a PCR and RT-PCR cloning strategy to allow sequence analysis of both genomic and transcribed copies. We identified two full-length copies of TrGP, some pseudogenes, and N- and C-terminal sequences of several genes. We also analyzed the expression and cellular localization of these proteins in epimastigote forms of a Venezuelan T. rangeli isolate using polyclonal antibodies made against a recombinant peptide from the N-terminal region of a TrGP member. We confirmed that TrGP is a multigenic family that shares many features with T. cruzi gp85/TS, including the telomeric location of some of its members, and by immunofluorescence analysis that its location is at the surface of the parasite.

Haplotype diversity in human mitochondrial DNA hypervariable regions I-III in the city of Caracas (Venezuela).

In order to expand the database of variable DNA for forensic identification purposes in Venezuela, we analyzed the sequence polymorphisms of mitochondrial DNA (mtDNA) hypervariable regions (HVR) I-III from 100 unrelated individuals from the city of Caracas, using PCR amplification and fluorescent-based capillary electrophoresis sequencing method. Dominant haplogroups corresponded to Native Americans followed by African ones. The inclusion of HVR III although useful for sub-haplogroup assignation, added little to the discrimination capacity of our database.

Current perceptions of Canadian autologous blood donors.

BACKGROUND AND OBJECTIVES: We determined the perceptions and motivations of autologous donors to establish their regard for this process and the new blood system established in 1999 in Canada. MATERIALS AND METHODS: Patients were surveyed before and after orthopaedic, cardiac, urological or gynecological procedures. RESULTS: Patients (n = 100; 57 men and 43 women) ranged in age from 19 to 83 years. Most had finished high school, and 21 had a university degree. Eighty-four had undergone previous surgery and 27 a previous transfusion. Fifty-one had been blood donors and 17 had been autologous donors. Specialists suggested donation to 78 of the patients. Seventy-two participated because they knew that their blood would be there. Three had a mistrust of the blood provider. Sixty-six believed that there is still a risk of receiving contaminated blood. Sixty-nine thought any risk was > or = 1 in 100,000; however, 16 thought the risk was < 1 in 1000. Postsurgery, 83 were happy to have donated their blood and 77 would do it again. Many felt that it improved their outcome. Most felt an increased sense of safety. Eighty-three patients were confident that the Canadian blood system had improved, but 17 were unsure. CONCLUSIONS: Concern about the safety of the allogeneic blood supply still drives the wish to autodonate. The process gives patients a sense of control and security. A large proportion of people felt that the Canadian blood system had improved, as determined by this 2003 study.

Perceptions and motivations of Canadian autologous blood donors.

Preoperative autologous blood donation in Canada has increased in the last decade due to concerns about allogeneic blood safety. As economic policies necessitate the validation of autologous blood donation, it is important to assess potential changes. This study examines the motivations and perceptions of patients participating in a Canadian autologous blood donation programme. The study was conducted at the Ottawa Hospital, Civic Campus. Questionnaires were developed and then administered to 100 consecutive adult autologous blood donors. The questionnaires assessed patient demographics, motivation for participation and perceptions about blood safety. Autologous donation was presented to 82% of patients as an option by their physicians. However, 59% of all patients felt that they were motivated to donate by their own fears. Patients (87%) also felt that directed blood donation should be offered due to their perception that directed donation is safer. Three-quarters of patients would be willing to pay for autologous donation. Patients are concerned about the safety of allogeneic blood and they are motivated to seek other alternatives despite the fact that allogeneic blood is very safe. These perceptions and motivations must be taken into account as health care policy changes are considered.

[Benzofurocaine analgesia in acute myocardial infarct]. / Analgeziia benzofurokainom pri ostrom infarkte miokarda.

A native non-narcotic analgetic agent benzofurcaine was used in 51 patients. It was shown that the analgetic activity of benzofurocaine had a dose-dependent character. Most effective was its use in doses of 2.1-2.7 mg/kg of body weight. It was established that the character of hemodynamic reactions due to benzofurocaine depended on the initial state of circulation. Benzofurocaine did not depress breathing. It is concluded that benzofuricaine is an effective means in moderate pain syndrome due to residual pain as well as in pain of pericardial genesis.

Potential metabolic mutagens of caffeine and various methylxanthines.

Xanthine N-carbinols, potential metabolites of caffeine and other methylxanthines, have been synthesized, characterized, and derivatized. Such intermediates, the initial metabolites arising from the cytochrome P-450 oxidation of the nitrogen-bound methyl groups, may be viewed as biological N-carbinols capable of alkylating proteins and nucleic acids. Evaluation of these compounds against Salmonella typhimurium, strain TA100, has demonstrated that, in contrast to caffeine, 7-hydroxymethyltheophylline and the 3,7-bis(hydroxymethyl)-1-methylxanthine mixture did exhibit cytotoxicity. There was no evidence of mutagenesis and it is possible that the Ames assay system is not applicable to N-carbinols.

Enantiomeric cannabinoids: stereospecificity of psychotropic activity.

The 1,1-dimethylheptyl homolog of (-)-(3R,4R)-7-hydroxy-delta-6- tetrahydrocannabinol (compound II) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED50 of (II).

Method for testing the sterility of total nutrient admixtures.

A test for determining the sterility of a total nutrient admixture (TNA) containing equal quantities of 10% fat emulsion (Liposyn II), 8.5% amino acids injection, and 50% dextrose injection using the USP membrane filtration procedure was developed and evaluated. Membrane filter selection was determined by analysis of flow rates, membrane fluid compatibility, bubble point stability, and rinse fluid requirements. Microbial challenges employing five organisms (Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) and both soybean casein digest and fluid thioglycollate media were used to confirm the ability of the test to detect low-level microbial contamination. A polyvinylidene fluoride membrane was determined to be the most appropriate of the membrane types studied because of its superior flow rate and membrane-fluid compatibility. Bubble point testing revealed no detrimental effects on the membrane. The potential problem of haziness caused by retention of the TNA by the membrane with subsequent release in the culture media (which could result in false-positive growth determinations) was diminished by using a sterile 0.1% peptone solution rinse and careful observation techniques. Performance of the sterility test by six hospital pharmacists required an average of 14.2 minutes. Sterility testing of alternate TNAs compounded with Intralipid and Nutralipid was not feasible because of prolonged filtration times. The basic USP membrane filtration procedure for large-volume injections can be used by hospital pharmacists for testing the sterility of TNAs. When fat emulsions are used in compounding, sterility-testing procedures specific to the emulsion product used should be developed and evaluated.

Stereochemical requirements for cannabimimetic activity.

The SAR of cannabimimetic activity in the cannabinoid series are reviewed with emphasis on the stereochemical requirements. Some new results are presented. The most important are that a, in humans, (-)-(1S)-delta-3-THC is much more active than (+)-(1R)-delta-3-THC; and b, with the 7-OH-delta-6-THC DMH enantiomers (32) and (33), the activity in several animal species resides completely in the (-)-(3R, 4R) enantiomer (32), the difference between the two enantiomers being up to several thousand times. The (3R,4R)-enantiomer (32) is much more active than delta-1- or delta-6-THC in animal tests, the exact level of activity depending on the test employed. The cannabimimetically inactive (+)-(3S,4S) enantiomer (33) was shown to be a potent analgetic in several animal tests. Thus, a complete dissociation between the cannabimimetic and the analgetic effects in a cannabinoid has been achieved, apparently for the first time.

Structure-anticonvulsant activity relationships of cannabidiol analogs.

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.

Cannabimimetic activity (delta 1-THC cue) of cannabidiol monomethyl ether and two stereoisomeric hexahydrocannabinols in rats and pigeons.

Animals (rats and pigeons) trained to discriminate between the presence and absence of the effects of delta 1-tetrahydrocannabinol (delta 1-THC; 3 and 0.56 mg/kg, respectively) were tested for generalization with graded doses of delta 1-THC as well as with two 7-hydroxyhexahydrocannabinol epimers which differ in the stereochemistry at the C-1 position only, and a cannabidiol (CBD)-like compound, cannabidiol monomethyl ether (CBDM). delta 1-THC produced dose/time related effects in both rats and pigeons. Both 7-hydroxyhexahydrocannabinols generalized with delta 1-THC in both species. Greater cannabimimetic activity was observed when the substituent at the C-1 position was equatorial (as in compound NL-105) than when the substituent was axial (compound NL-106) (for chemical structures see Fig. 1, below). Thus in the absence of other substituents the planarity at the C-1 position determines cannabimimetic activity. CBDM induced only vehicle appropriate responding at the doses of 3 and 10 mg/kg in both species; 30% delta 1-THC appropriate responding occurred with 17.5 mg/kg (only tested in pigeons), a dose which also appeared to excert rate depressant effects. Thus, like CBD, CBDM has a low degree of cannabimimetic activity.

Specific impairment of ADP-induced platelet aggregation by cannabinoids.

The structure-activity relationship of the inhibition of ADP-induced platelet aggregation by cannabinoids was studied. A marked specificity was revealed: derivatives in which the two asymmetric centers have a configuration opposite to that of the natural cannabinoids and have a dimethylheptyl (DMH) side-chain were most inhibitory. It is concluded that the mode of inhibition includes a specific interaction of the cannabinoids with some membrane proteins, possibly including the receptor for ADP.

Conformation, dynamics, and structural transitions of the TATA box region of self-complementary d[(C-G)n-T-A-T-A-(C-G)n] duplexes in solution.

Structural and kinetic features of the TATA box located in the center of the alternating self-complementary d(C-G-C-G-T-A-T-A-C-G-C-G) duplex (TATA 12-mer) and d(C-G-C-G-C-G-T-A-T-A-C-G-C-G-C-G) duplex (TATA 16-mer) have been probed by high-resolution proton and phosphorus NMR spectroscopy in aqueous solution. The imino exchangeable Watson-Crick protons and the nonexchangeable base protons in the TATA box of the TATA 12-mer and TATA 16-mer duplexes have been assigned from intra and inter base pair nuclear Overhauser effect (NOE) measurements. Imino proton line-width and hydrogen exchange saturation recovery measurements demonstrate that the dA X dT base pairs in the TATA box located in the center of the TATA 12-mer and TATA 16-mer duplexes are kinetically more labile than flanking dG X dC base pairs. The proton and phosphorus NMR parameters of the TATA 12-mer monitor a cooperative premelting transition in the TATA box prior to the onset of the melting transition to unstacked strands. Phosphorus NMR studies have been unable to detect any indication of a right-handed B DNA to a left-handed Z DNA transition for the TATA 12-mer duplex in saturated NaCl solution. By contrast, we do detect the onset of the B to Z transition for the TATA 16-mer in saturated NaCl solution. Proton and phosphorus NMR studies demonstrate formation of a loop conformation with chain reversal at the TATA segment for the TATA 12-mer and TATA 16-mer duplexes on lowering the DNA and counterion concentration. The imino protons (10-11 ppm) and phosphorus resonances (3.5-4.0 ppm; 4.5-5.0 ppm) of the loop segment fall in spectral windows well resolved from the corresponding markers in fully paired segments so tha it should be possible to identify loops in longer DNA helixes. The equilibrium between the loop and fully paired duplex conformations of the TATA 12-mer and TATA 16-mer is shifted toward the latter on addition of moderate salt.

Activity of novel aminocannabinoids in baboons.

The axial and equatorial isomers of 7-(methylamino)hexahydrocannabinol (1 and 2) and 7-(dimethylamino)hexahydrocannabinol (3 and 4) were prepared by reductive amination of the corresponding cannabinoid aldehydes. The amines caused some tranquility in baboons but did not evoke the typical cannabimimetic syndrome caused by psychoactive cannabinoids. However the axial amines (1 and 3) but not the equatorial ones (2 and 4) caused bouts of scratching and yawning. The latter is a rare pharmacological effect hitherto not observed with other cannabinoids.

Anticonvulsant effects of the (-) and (+)isomers of cannabidiol and their dimethylheptyl homologs.

The anticonvulsant actions of the (-) and (+)isomers of cannabidiol and dimethylheptyl-cannabidiol were studied with the maximal electroconvulsive shock model in mice. The ratio of the times for hindlimb extension and fore limb flexion was recorded as an anticonvulsant index. All the cannabinoids were anticonvulsant. They also potentiated pentobarbitone sleeping time. The (+)isomer was more active than the (-)isomer. Possible mechanisms of actions on receptors or membranes are discussed.

Stereochemical requirements for cannabinoid activity.

Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ only in that the chemical groupings in one of them at C-1, C-2 are situated at C-1, C-6 in the other (but retain their stereochemistry) have almost equivalent psychotropic activity.