The effects of assisted cycling therapy (ACT) and voluntary cycling on reaction time and measures of executive function in adolescents with Down syndrome.

BACKGROUND: Reports of positive effects of aerobic exercise on cognitive function in persons with Down syndrome are extremely limited. However, a novel exercise intervention, termed assisted cycling therapy (ACT), has resulted in acutely improved cognitive planning ability and reaction times as well as improved cognitive planning after 8 weeks of ACT in adolescents and young adults with Down syndrome. Here, we report the effects of 8 weeks of ACT on reaction time, set-shifting, inhibition and language fluency in adolescents with Down syndrome. METHODS: Adolescents with Down syndrome (age: ~18 years) were randomly assigned to 8 weeks of ACT (n = 17) or voluntary cycling (VC: n = 16), and a convenience sample (n = 11) was assigned to be an inactive comparison group (NC: n = 11). During ACT, the cycling cadence of the participants was augmented to an average cadence that was 80% faster than the voluntary cadence of the VC group. The increase in cadence was achieved with an electric motor in the stationary bicycle. Reaction time, set-shifting, inhibition and language fluency were assessed before and after 8 weeks of intervention. RESULTS: Power output and heart rates of the ACT and VC groups were almost identical, but the ACT cadence was significantly faster. The ACT group, but not the VC or NC groups, showed significantly improved reactions times (Hedges' g = -0.42) and inhibitory control (g = 0.18). Only the VC group showed improved set-shifting ability (g = 0.57). The ACT and VC groups displayed improved semantic language fluency (g = 0.25, g = 0.22, respectively). DISCUSSIONS: These and previous results support the hypothesis of increased neuroplasticity and prefrontal cortex function following ACT and, to a smaller extent, following VC. Both ACT and VC appear to be associated with cortical benefits, but based on current and previous results, ACT seems to maximize the benefits.

Reversal of handedness effects on bimanual coordination in adults with Down syndrome.

BACKGROUND: Research on unimanual tasks suggested that motor asymmetries between hands may be reduced in people with Down syndrome. Our study examined handedness (as assessed by hand performance) and perceptual-motor integration effects on bimanual coordination. METHODS: Adults with Down syndrome (13 non-right-handed, 22 right-handed), along with comparison groups of adults (16 non-right-handed, 21 right-handed) and children (15 non-right-handed, 22 right-handed) without Down syndrome, drummed with auditory, verbal and visual instructions. RESULTS: In contrast to handedness effects in the children and adults without Down syndrome, right-handed participants with Down syndrome led more with the left hand, and had lower coordination stability than non-right-handed participants with Down syndrome. CONCLUSIONS: The reversed handedness effect during bimanual coordination suggests a complex relationship between handedness and task requirements in adults with Down syndrome.

Therapeutic potential of egg yolk antibodies for treating Clostridium difficile infection.

Herein we present evidence for the therapeutic potential of colonization factor (CF)-specific egg yolk antibodies (IgY) for potentially treating acute and recurring Clostridium difficile infection (CDI) in humans. The study involved cloning, expressing as 6×His-tagged proteins in Escherichia coli, and Ni-affinity purifying three previously identified CFs (FliC, FliD and Cwp84) from C. difficile. The recombinant CF antigens were then used to immunize Leghorn chickens and CF-specific IgY antibodies were prepared from their eggs. The specificity and titre of the resulting C. difficile CF-specific IgY antibodies were assessed by ELISA and Western immunoblotting techniques. The antibodies were also screened for their ability to inhibit C. difficile adherence to human colon-derived T84 cells, and, based on these findings, one of them (FliD-specific IgY) was evaluated for its potential to prevent C. difficile-mediated morbidity and mortality in Syrian hamsters. The results revealed that purified FliD-specific IgY significantly protected hamsters from C. difficile strain 630 infection relative to control animals treated with carbonate buffer alone or IgY produced from unimmunized chicken eggs. The results suggest that egg yolk preparations obtained from chickens immunized with recombinant C. difficile CFs may represent another safe and cost-effective treatment option in humans suffering from acute or recurring CDI.

Persons with and without Down syndrome use similar strategies when using visual instructions for bimanual drumming.

BACKGROUND: Previous research suggested that persons with Down syndrome (DS) used a different strategy to drum than typical adults. METHODS: The present study examined continuous bimanual drumming strategies in response to different instructions in 10 persons with DS, 10 mental age-matched and 10 chronological age-matched groups. The drumming task required participants to hit two drums with the drumsticks at the same time following verbal (e.g. 'up' and 'down'), visual (e.g. video of both drumsticks moving up and down together) or auditory (e.g. sound of both drums being hit, then cymbal being hit) instructions for 10 s. Sensors placed on the wrists of each participant and the end of each drumstick provided data that allowed the assessment of individual drumming strategies. RESULTS: In general, when persons with DS were following the visual instructions their drumming movements were shorter, straighter and less variable as compared with their movements in the auditory and verbal conditions. CONCLUSIONS: Whether movement paths were straight or curved, the strategy was to move the drumstick and wrist together as one unit.

The use of (symmetry) group theory as a predictive tool for studying bimanual coordination.

Symmetry groups-rules that connect different configurations of a given set of components-represent a compact means of coding for effects, a feature that is desirable in both model- and theory-building. The present study was designed to compare the effects of spatial orientation differences with the various other asymmetries (e.g., timing differences, handedness preferences, the direction of attention) that are accommodated by current models of bimanual coordination. The authors used symmetry groups to predict specific patterns of results. In 2 experiments, participants (N = 13, Experiment 1; N = 9, Experiment 2) coordinated the movements of differently oriented (1 downward and 1 upward) pendulum pairs at a low (0.62 Hz) or high (0.82 Hz) movement frequency to establish an in-phase or antiphase pattern. Consistent with previous results (P. G. Amazeen, E. L. Amazeen, & M. T. Turvey, 1998a), the downward-oriented pendulum tended to lead slightly. In contrast to the effects of other bimanual asymmetries, the downward-oriented pendulum lead was amplified at low frequencies. Although the results contradicted the predictions of existing models of bimanual coordination, they were consistent with predictions from symmetry group theory. In the discussion, the authors focus on the application of symmetry groups to both bimanual coordination and other phenomena with more complex symmetric structures.

Glycan mimicry as a basis for novel anti-infective drugs.

The idea of using carbohydrate-based drugs to prevent attachment of microbial pathogens to host tissues has been around for about three decades. This concept evolved from the observation that many pathogenic microbes bind to complex carbohydrate sequences on the surface of host cells. It stands to reason, therefore, that analogs of the carbohydrate sequences pathogens bind to could be used to competitively inhibit these interactions, thereby preventing microbial damage to the host. This article will summarize some of the recent advances in developing such carbohydrate-based anti-infective drugs.

Immunoprophylactic potential of cloned Shiga toxin 2 B subunit.

The Shiga toxins Stx1 and Stx2 contribute to the development of enterohemorrhagic O157:H7 Escherichia coli-mediated colitis and hemolytic-uremic syndrome in humans. The Stx2 B subunit, which binds to globotriaosylceramide (GB3) receptors on target cells, was cloned. This involved replacing the Stx2 B subunit leader peptide nucleotide sequences with those from the Stx1 B subunit. The construct was expressed in the TOPP3 E. coli strain. The Stx2 B subunits from this strain assembled into a pentamer and bound to a GB3 receptor analogue. The cloned Stx2 B subunit was not cytotoxic to Vero cells or apoptogenic in Burkitt's lymphoma cells. Although their immune response to the Stx2 B subunit was variable, rabbits that developed Stx2 B subunit-specific antibodies, as determined by immunoblot and in vitro cytotoxicity neutralization assays, survived a challenge with Stx2 holotoxin. This is thought to be the first demonstration of the immunoprophylactic potential of the Stx2 B subunit.

Outcomes of an educational activity with Victorian GPs aimed at improving knowledge and practices in relation to sexually transmissible diseases.

OBJECTIVE: To measure the effect of a simple educational strategy for general practitioners (GPs) on their knowledge and self-reported practice in relation to sexually transmissible disease (STD) management. METHOD: In 1995, we surveyed 520 Victorian GPs; 444 (85%) responded. A sub-sample of 242 was sent an educational package in relation to STD management that required them to reflect on their performance in the survey in relation to that of the sample as a whole. Two months after they had received the package, a brief follow-up questionnaire, using a selection of questions from the first survey, was sent to these GPs. RESULTS: Practitioners showed statistically significant improvements in knowledge and self-reported practice for four of the six outcomes that were examined. CONCLUSION: A relatively simple educational package for GPs had a high participation rate and resulted in improvements in knowledge and self-reported practice that could contribute to increased STD case finding in the general practice setting. IMPLICATIONS: The key to enabling GPs to make a greater contribution to improved STD control is to encourage them to be more active in diagnosing and treating asymptomatic disease. For asymptomatic patients, sexual history-taking and selective screening are important skills but there are barriers to their implementation in the general practice setting. A key objective of GP educational programs in relation to STDs is to increase their likelihood of taking a sexual history and the significant increase in this measure for the whole sample was encouraging.

Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands.

The diseases caused by Shiga and cholera toxins account for the loss of millions of lives each year. Both belong to the clinically significant subset of bacterial AB5 toxins consisting of an enzymatically active A subunit that gains entry to susceptible mammalian cells after oligosaccharide recognition by the B5 homopentamer. Therapies might target the obligatory oligosaccharide-toxin recognition event, but the low intrinsic affinity of carbohydrate-protein interactions hampers the development of low-molecular-weight inhibitors. The toxins circumvent low affinity by binding simultaneously to five or more cell-surface carbohydrates. Here we demonstrate the use of the crystal structure of the B5 subunit of Escherichia coli O157:H7 Shiga-like toxin I (SLT-I) in complex with an analogue of its carbohydrate receptor to design an oligovalent, water-soluble carbohydrate ligand (named STARFISH), with subnanomolar inhibitory activity. The in vitro inhibitory activity is 1-10-million-fold higher than that of univalent ligands and is by far the highest molar activity of any inhibitor yet reported for Shiga-like toxins I and II. Crystallography of the STARFISH/Shiga-like toxin I complex explains this activity. Two trisaccharide receptors at the tips of each of five spacer arms simultaneously engage all five B subunits of two toxin molecules.

Attitudes to taking a sexual history in general practice in Victoria, Australia.

OBJECTIVE: To examine general practitioners' (GPs') attitudes towards taking a sexual history. METHODS: Questions on sexual history taking were included in a random survey on the STD knowledge, attitudes, and practices of 600 GPs practising in Victoria, Australia. RESULTS: Most GPs commonly asked patients about safe sex (79%), number of sex partners (63%), and injecting drug use (60%) while fewer asked about recent overseas travel (50%) and sex with sex workers (31%). GPs who performed sexual health consultations daily or weekly identified barriers to sexual history taking to be of less concern than those who performed such consultations infrequently. Most GPs (92%) would take a sexual history from a man presenting as the sexual contact of an infected partner, but less than a third would do so for a patient routinely requesting the contraceptive pill (28%), a Papanicolaou (Pap) smear (30%), or advice about immunisation before overseas travel (30%). Female GPs were significantly more likely than male GPs to take a sexual history in those clinical situations involving a female patient and also to perceive these patients as experiencing less embarrassment. CONCLUSIONS: This study highlights both the lack of opportunistic sexual history taking and the main barriers to sexual history taking in general practice in Victoria, Australia. The importance of educating both patients and GPs about sexual history taking are discussed.

Maximising response rates in a survey of general practitioners. Lessons from a Victorian survey on sexually transmissible diseases.

OBJECTIVE: To describe factors that influence participation by general practitioners (GPs) in survey research, and in particular to examine the effectiveness of telephone prompts made by a GP researcher compared with non-medical researchers in a survey of GPs on sexually transmissible diseases (STDs). DESIGN AND SETTING: A questionnaire survey of knowledge, attitudes, behaviour and practice (KABP) in relation to STDs was distributed to 520 Victorian GPs randomly selected from the Australian Medical Publishing Company's (AMPCo) database of Australian medical practitioners. MAIN OUTCOME MEASURES: Number of GPs able to be contacted by telephone and cumulative and overall response rates to the questionnaire. RESULTS: The overall response rate was 85%. Although the GP researcher was able to make contact by telephone in a higher proportion of cases (80%) than the non-GP researchers combined (69%, p < 0.01) response rates were not significantly different (83% versus 87%). CONCLUSIONS: Telephone prompts to encourage GP response in survey research need not be made by a medical practitioner. Other important factors in relation to response rate that should be considered by researchers are GP involvement in the developing and piloting of the survey instrument, incentives and provision of detailed feedback of the results of the survey.

Managing people with HIV/AIDS--the involvement of Victorian general practitioners.

OBJECTIVE: To examine aspects of knowledge, attitudes, behaviour and practice (KABP) of Victorian general practitioners (GPs) in relation to human immunodeficiency virus (HIV), as part of a larger KABP study relating to GPs and sexually transmissible diseases (STDs). METHOD: Questionnaire survey of 520 randomly selected GPs. RESULTS: A response rate of 85% was obtained. Most respondents were aware of the major risk factors for HIV infection and most GPs obtained consent before HIV testing. More than 22% of respondents had ordered an HIV test that was positive and 39% had been involved with the management of HIV positive patients (asymptomatic, symptomatic or both). The gender of the practitioner (male), greater frequency of STD diagnosis and greater level of ease in treating homosexual men were all significantly associated with having ordered an HIV test that was positive and with ongoing management of asymptomatic and symptomatic HIV positive patients, whereas practitioner age, frequency of advising on safe sex and providing contraceptive advice were not. CONCLUSION: Thirty-nine per cent of Victorian GPs are now managing HIV positive patients, representing a 17% increase since 1989. We found that GP knowledge of HIV transmission and infection control was generally good although information on knowledge and practice beyond initial diagnosis was not sought. Given the evidence of a significant association between practitioner experience in HIV/AIDS management and survival of their patients, there is a need for further research into the educational and support needs of Australian GPs in relation to this increasingly complex area of clinical practice.

Sexually transmissible diseases--knowledge and practices of general practitioners in Victoria, Australia.

OBJECTIVE: To examine knowledge and practices in relation to sexually transmissible diseases (STDs) of general practitioners (GPs) in Victoria, Australia. METHOD: A questionnaire was distributed to 520 Victorian GPs randomly selected from the Australian Medical Publishing Company (AMPCo) database of Australian medical practitioners. RESULTS: A response rate of 85% was obtained. While sexual health consultations were common for Victorian GPs, STD caseloads were generally low. Knowledge of clinical features of symptomatic STDs and of important STD epidemiology was generally good although there was a lower awareness of the asymptomatic nature of the most prevalent STDs in Victoria. Diagnostic tests were generally selected appropriately although many GPs did not perform the gold standard combination of tests required for adequate differential diagnosis. Level of STD STD knowledge was related to frequency of advising about safe sex, diagnosing STDs, and younger practitioner age. Attendance at any of a number of postgraduate courses of relevance to the management of STDs was not related to better STD knowledge overall. CONCLUSIONS: Prevention and detection of STDs in general practice involve risk assessment and screening of asymptomatic patients as well as effective treatment of symptomatic patients and their contacts. Results presented here suggest that GPs have good knowledge and use appropriate investigations for patients presenting with symptoms of an STD. The low levels of awareness of the asymptomatic nature of many STDs and other particular aspects of STD knowledge and practice should be addressed in undergraduate and postgraduate medical education programmes.

Contact tracing and sexually transmitted disease among aboriginal men on the Anangu Pitjantjatjara lands.

Sexually transmitted diseases (STDs) are a major health problem for Pitjantjatjara Aboriginal people, causing considerable morbidity and being implicated in the potential rapid transmission of human immunodeficiency virus (HIV) infection. This paper presents data in relation to STD contact tracing on the Anangu Pitjantjatjara lands. In-depth interviews were conducted with Aboriginal men and non-Aboriginal clinic staff to ascertain their attitudes to and perceptions of contact tracing. The interviews with Aboriginal men also sought more general information in relation to health-seeking behaviour and knowledge of STDs. While contact tracing has proven an effective method of case detection on the Anangu Pitjantjatjara lands (most named contacts are able to be located and a high proportion are found to be infected), the data suggest that important constraining issues are the reluctance of Aboriginal men to consult with particular health workers because of moiety group considerations, concerns about confidentiality, and the low level of knowledge of STDs, particularly of largely asymptomatic infections such as chlamydia, syphilis and HIV.

Role of a brush border membrane fatty acid binding protein in oleic acid uptake into rat and rabbit jejunal brush border membrane.

Oleic acid uptake was studied using adult rat and rabbit jejunal brush border membrane vesicles. The intestinal uptake of oleic acid is influenced by the activity of an amiloride-inhibitable brush border membrane Na+/H+ exchanger, NHE3: opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. This study was undertaken to test the hypothesis that a portion of oleic acid uptake is facilitated by a fatty acid binding protein in the brush border membrane (FABPPM) of adult rat jejunum. There was a reduction in the uptake of oleic acid when brush border membrane vesicles were incubated with a rat liver plasma membrane fatty acid binding protein antibody (anti-FABPPM-Ab) in the absence, but not in the presence, of opposing Na+/H+ gradients. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, as well as by a process which involves the activation of the brush border membrane Na+/H+ exchanger, and a membrane fatty acid binding protein.

Oleic acid uptake into rat and rabbit jejunal brush border membrane.

Oleic acid uptake was studied using adult rabbit and rat jejunal brush border membrane vesicles. There was a reduction of oleic acid uptake following trypsin-treatment. Opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. The addition of mucin further increased the enhanced uptake of oleic acid observed in the presence of opposing Na+/H+ gradients. Amiloride, an inhibitor of the Na+/H+ exchanger, reduced by about 40% the uptake of oleic acid into sheets of rat jejunum, and this inhibitory effect was observed over a range of rates of stirring of the bulk phase. In rabbit jejunal brush border membrane vesicles, amiloride reduced oleic acid uptake in the presence but not in the absence of opposing Na+/H+ gradients, with a Ki of approx. 36 microM. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, influenced by a process which involves the activation of the brush border membrane Na+/H+ exchanger.

Epidemic gonococcal conjunctivitis in central Australia.

OBJECTIVES: To describe an epidemic of gonococcal conjunctivitis in central Australian Aboriginal children, the responsible phenotypes of Neisseria gonorrhoeae, factors facilitating spread and treatment efficacy. DESIGN: Prospective study of patients with laboratory confirmed or clinical gonococcal conjunctivitis diagnosed from January to July 1991. SETTING: The Alice Springs and Barkly Tablelands Health Districts of the Northern Territory, the Anangu Pitjantjatjara Lands of South Australia and the Ngaanyatjarra Homelands of Western Australia. METHODS: Cases were identified from surveillance data and laboratory notifications, and by active case finding. A community survey explored risk factors. MAIN OUTCOME MEASURES: Age-specific attack rates, auxotype/serovar characterisation of isolates, and clinical response to single dose treatment. RESULTS: We identified 432 cases. The highest attack rate was in the 0-4 year age group (86 per 1000), and the risk of conjunctivitis decreased with age. The odds ratio of secondary infection in household compared with community contacts was 14.5 (P < 0.002; 95% CI, 1.8-120.0). Disease was less common in children with clean faces and hands. The outbreak occurred after unseasonable rains and large community gatherings. Isolates were predominantly IA serovars, less common among central Australian serovars. CONCLUSIONS: The trigger for nonsexually transmitted gonococcal conjunctivitis epidemics remains obscure. Age is a significant risk factor and social and ecological factors may also contribute. Active case finding within affected households and treatment with a suitable penicillin is effective in stopping transmission.

Feeding an isocaloric omega-3 fatty acid diet reduces the brush border membrane vesicle uptake of glucose in streptozotocin-diabetic rats.

Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modified further by manipulation of the type of fatty acids in the triglycerides in the diet. Jejunal brush border membrane vesicles were used to examine the uptake of D-glucose into the jejunum of non-diabetic control and streptozotocin-diabetic rats fed for two weeks in isocaloric semisynthetic diet enriched with saturated fat (beef tallow) or polyunsaturated omega-3 fatty acids (fish oil). The time-course of uptake of 100 microM glucose demonstrated an overshoot which peaked at approximately 30 seconds and declined thereafter to an equilibrium plateau. In concentration studies, glucose uptake was greater into brush border membrane vesicles of diabetic as compared with control rats. The maximal transport rate (Vmax) was increased approximately 9-fold in diabetics as compared with control rats fed beef tallow (p < 0.05), and was increased approximately 6-fold in diabetic rats fed fish oil. In diabetic rats, feeding fish oil reduced the value of the Vmax by approximately 50% as compared with diabetic rats fed beef tallow. Thus, the enhanced glucose uptake into BBM vesicles of streptozotocin-diabetic rats can be partially corrected by feeding an isocaloric semisynthetic diet enriched with polyunsaturated omega-3 fish oils.