A pilot randomised control trial of the efficacy of stability-based training with visualisation for people with chronic ankle instability.

Chronic ankle instability (CAI) is associated with recurring symptoms that inhibit daily activity. Stability-based rehabilitative training is recommended for CAI. Visualisation (VIS) produces real-time feedback using motion capture and virtual reality. This pilot study aimed to determine the feasibility, adherence, safety, and efficacy of incorporating VIS into stability training for people with CAI. Efficacy was examined through effect of VIS training on dynamic stability, perception of stability, and rehabilitative experience. Individuals with CAI completed a 4-week stability-based training programme with VIS, or without visualisation (NO-VIS). Participants completed the Star Excursion Balance Test (SEBT) and Cumberland Ankle Instability Tool (CAIT) prior to, and after training. Enjoyment of training was recorded using the Physical Activity Enjoyment Scale (PACES-8). Of 17 participants (VIS = 10, NO-VIS = 7), there were 2 drop outs (VIS = 1, NO-VIS = 1). No adverse events were reported, and participant drop-out was due to injury unrelated to the study. The VIS group showed a significantly greater increase in average SEBT reach distance (d = 1.7, p = 0.02). No significant differences were reported for the CAIT or PACES-8. This study supports the feasibility and safety of stability-based training with VIS in those with CAI. The enhanced performance outcome on the SEBT suggests VIS may enhance stability-based training.

In Vitro and In Vivo Recording of Local Field Potential Oscillations in Mouse Hippocampus.

Oscillations in hippocampal local field potentials (LFP) reflect the coordinated, rhythmic activity of constituent interneuronal and principal cell populations. Quantifying changes in oscillatory patterns and power therefore provides a powerful metric through which to infer mechanisms and functions of hippocampal network activity at the mesoscopic level, bridging single-neuron studies to behavioral assays of hippocampal function. Here, complementary protocols that enable mechanistic analyses of oscillation generation in vitro (in slices and a whole hippocampal preparation) and functional analyses of hippocampal circuits in behaving mice are described. Used together, these protocols provide a comprehensive view of hippocampal phenotypes in mouse models, highlighting oscillatory biomarkers of hippocampal function and dysfunction. Curr. Protoc. Mouse Biol. 2:273-294 © 2012 by John Wiley & Sons, Inc.

Genetic variation in hepatic glucose-6-phosphatase system genes in cases of sudden infant death syndrome.

Genetic deficiencies of the hepatic glucose-6-phosphatase system, either of the enzyme (G6PC1) or of the glucose-6-phosphate transporter (G6PT1), result in fasting hypoglycaemia. Low hepatic G6PC1 activities were previously reported in a few term sudden infant death syndrome (SIDS) infants and assumed to be due to G6PC1 genetic deficiencies. In preterm infants, failures of postnatal activation of G6PC1 expression suggest disordered development as a novel cause of decreased G6PC1 activity in SIDS. G6PC1 and G6PT1 functional and mutational analysis was investigated in SIDS and non-SIDS infants. G6PC1 hepatic activity was abnormally low in 98 SIDS (preterm, n=13; term, n=85), and non-SIDS preterm infants (n=35) compared to term non-SIDS infants (n=29) and adults (n=9). Mean glycogen levels were elevated, except in term non-SIDS infants. A novel G6PT1 promoter polymorphism, 259C --> T was found; the - 259*T allele frequency was greater in term SIDS infants (n=140) than in term control infants (n=119) and preterm SIDS infants (n=30). Heterozygous and homozygous prevalence of 259C --> T was 38.6% and 7.1%, respectively, in term SIDS infants. In cell-based expression systems, the presence of - 259T in the promoter decreased basal luciferase activity by 3.2-fold compared to - 259C. Glucose-6-phosphatase latency in hepatic microsomes was elevated (indicating decreased G6PT1 function) in heterozygous and homozygous - 259T states. Delayed postnatal appearance of hepatic glucose-6-phosphatase in infants makes them vulnerable to hypoglycaemic episodes and this may occur in some SIDS infants. However, SIDS may be an association of more complex phenotypes in which several genes interact with multiple environmental factors. A UK-wide DNA Biobank of samples from all infant deaths, with an accompanying epidemiological database, should be established by pathologists to allow cumulative data to be collected from multiple genetic investigations on the same large cohort of samples, with the aim of selection of the best combination of genetic markers to predict unexpected infant death.

Thyroid hormone potentiates glucocorticoid-evoked airway Na+ transport without affecting alpha-ENaC transcription.

Glucocorticoid and thyroid hormones (T3) are important for the development of the lungs' Na+ absorbing phenotype, which is essential for the integrated functioning of the respiratory tract. Electrometric studies of H441 airway epithelial cells confirmed that dexamethasone increases apical Na+ conductance (GNa) and demonstrated that T3 facilitates this control over GNa. Assays of transcriptional activity showed that dexamethasone caused concentration-dependent activation of the human alpha-ENaC promoter (EC50 approximately 5 nM) but, despite its clear effect on GNa, T2 had no effect upon the transcriptional response to dexamethasone. The facilitation of Na+ transport may thus reflect control over events downstream to transcription.

Polymorphisms in genes involved in glucose metabolism in cases of sudden infant death syndrome.

BACKGROUND: Infants with intra-uterine growth retardation have an increased risk of Sudden Infant Death Syndrome (SIDS). Hypoglycaemia is also significantly correlated with retardation of intra-uterine growth. A number of mutations in key proteins involved in regulation of blood glucose (e.g. glucokinase) have been found to result in reduced birth weight. Heterozygous mutations in the coding region of the glucokinase gene have been shown to cause MODY (a form of early onset Type II diabetes mellitus). The aim was to screen a cohort of SIDS and control infants who were either growth retarded or appropriately grown for gestational age to determine if any mutations and/or polymorphisms were present in the glucokinase gene. METHODS: PCR, denaturing high performance liquid chromatography on an automated Transgenomic WAVE DNA fragment analysis system and DNA sequencing. RESULTS: Genomic DNA was isolated from 129 infants who were either growth retarded or appropriately grown for gestational age. We found several rare novel polymorphisms in the glucokinase gene in the infant samples. However, none of the samples contained any of the mutations in the glucokinase gene previously reported in cases of MODY. CONCLUSIONS: We have found rare novel polymorphisms in the glucokinase gene in the infant samples. In contrast in these samples, we have not found any examples of the previously reported mutations in the coding region of the glucokinase gene found in MODY. This clearly shows that while MODY babies are often small, MODY is not a common cause of either intra-uterine growth retardation or of SIDS.

Maintenance of physical activity following an individualized motivationally tailored intervention.

This study examined predictors of exercise maintenance following completion of a physical activity intervention. Sedentary adults recruited through newspaper advertisements were randomly assigned to receive either (a) a motivation-matched intervention with feedback reports that were individually tailored (IT) to psychological variables from social cognitive theory and the Transtheoretical Model via computer expert system, or (b) a standard, print-based intervention (ST). The intervention phase of the study included mailed assessments and intervention materials at baseline, 1, 3, and 6 months. An assessment-only follow-up was conducted 6 months after the end of the intervention (Month 12). Participants were assessed for current physical activity participation, motivational readiness for physical activity, a number of psychological constructs posited to influence participation in physical activity (e.g., self-efficacy), and current affect. Significantly more participants in the IT condition met or exceeded exercise participation goals at the end of the intervention period and maintained this level of physical activity through the Month 12 follow-up compared to ST participants. Prospective analyses revealed significant differences in several psychological constructs both at program entry (baseline) and the end of the intervention period between individuals who maintained their physical activity participation through Month 12 and those who did not. Results suggest that the maintenance of physical activity following the end of an active intervention program may be influenced by attitudes and behaviors acquired along with increased participation in physical activity, as well as by preexisting characteristics that individuals bring into treatment.

Interactive communication strategies: implications for population-based physical-activity promotion.

Physical inactivity is a recognized independent risk factor for the development of cardiovascular disease. However, a large proportion of the U.S. population does not participate in regular physical activity, and research has shown that without intervention, most people remain sedentary. Thus, an urgent need exists for developing effective interventions to promote physical-activity adoption and maintenance. Additionally, it is important that these interventions can be disseminated to the large population of sedentary individuals. To be disseminable, physical-activity interventions must move beyond reliance on strictly face-to-face modes and begin to more fully use newer technologies, such as the Internet. This article summarizes the progress made in promoting physical activity with interactive communications. We also delineate areas for future research.

Physical activity behavior change: issues in adoption and maintenance.

The many benefits of participation in regular moderate- or vigorous-intensity physical activity are well established, yet more than 60% of the population is sedentary or insufficiently active. Published studies have revealed that behavior modification and cognitive-behavior modification can be successfully used to assist patients, healthy adults, and youth in the adoption of physically active lifestyles. However, few studies with adults and youth have examined the maintenance of physical activity behavior beyond 6 months of adoption of this behavior. Maintenance of physical activity is critically important because ongoing participation in the behavior is necessary to sustain health benefits. Knowledge of effective intervention strategies for long-term maintenance of physical activity is at an early stage. The authors provide a summary of what is known about the maintenance of physical activity behavior in adults and youth and how physical activity behavior relates to other health behaviors such as smoking, as well as recommendations for research on physical activity behavior change and maintenance.

Serrate1-induced notch signalling regulates the decision between immunity and tolerance made by peripheral CD4(+) T cells.

Signals derived from antigen-presenting cells (APC) influence the functional differentiation of CD4(+) T cells. We report here that Serrate1 (Jagged1), a ligand for the Notch1 receptor, may contribute to the differentiation of peripheral CD4(+) T cells into either helper or regulatory cells. Our findings demonstrate that antigen presented by murine APC overexpressing human Serrate1 induces naive peripheral CD4(+) T cells to become regulatory cells. These cells can inhibit primary and secondary immune responses, and transfer antigen-specific tolerance to recipient mice. Our results show that Notch signalling may help explain 'linked' suppression in peripheral tolerance, whereby tolerance induced to one epitope encompasses all epitopes on that antigen during the course of an immune response.

Body image evaluations in obese females with binge eating disorder.

Dimensions of body image in a sample of obese women diagnosed with binge eating disorder (BED; N=42) were compared with a sample of obese women without BED (non-BED; N=42), matched on age and BMI. Additionally, the relationship between BED, body image and several dimensions of treatment response was examined. Results indicated BED women were more likely to negatively evaluate their global physical appearance and have less satisfaction with specific areas of the body than were non-BED women, even after controlling for depression scores. While BED women were significantly more likely to endorse depressive symptoms, depression scores were negatively correlated with body satisfaction in non-BED women only. BED women did not fare worse in formal weight-loss treatment, as measured by length of time in treatment, group-therapy attendance, or BMI at posttreatment. The role of body image in women with BED seeking weight-loss treatment is discussed relevant to the context of potential impact of BED and negative body image on active weight-loss treatment and maintenance.

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known. OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects. METHODS: Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study. Medical history, physical examination, laboratory studies, and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period. RESULTS: No severe adverse effects were observed related to the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients. CONCLUSION: Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.

Tissue damage in cattle infected with Theileria annulata accompanied by metastasis of cytokine-producing, schizont-infected mononuclear phagocytes.

The distribution of schizont-infected cells in six calves undergoing acute, lethal sporozoite-induced infections with Theileria annulata was examined, the calves being killed in the early, middle or late stages of disease. A combination of histological and immunocytochemical techniques showed that schizont-infected cells became disseminated rapidly through the lymphoid tissues from the prescapular lymph node draining the site of inoculation to distant lymph nodes (e.g., precrural, mesenteric and mediastinal) and to the spleen and thymus. The parasitized cells also spread rapidly into non-lymphoid organs, being found in the liver, kidney, lung, abomasum, adrenal glands and pituitary gland by day 7, in the brain by day 12 and in the heart by day 14 after infection. As infection progressed, the schizonts differentiated into merozoites. By the late stages of disease, the cells containing merozoites greatly out-numbered schizont-infected cells. The parasitized mononuclear cells were labelled by antibodies to bovine interferon-alpha1 and tumour necrosis factor-alpha and, during the later stages of the disease, contained erythrocytes parasitized by piroplasms. The results suggested that the parasitized mononuclear cells themselves played a role in the development of clinical disease and in tissue damage. These findings provide new evidence that tropical theileriosis can no longer be viewed as a lymphoproliferative disease resulting from the uncontrolled multiplication and metastasis of lymphoid cells infected with T. annulata schizonts, but is caused by a parasite that lives in, and is disseminated by, cytokine-secreting, proliferating mononuclear phagocytes.

How are we doing with physical activity?

An estimated 60% of U.S. adults are inactive or underactive, and nearly half of America's youth (aged 12 to 21 years) are not vigorously active on a regular basis. Downstream interventions provide individual strategies that effectively increase short-term participation in physical activity by 10% to 25%. Downstream and midstream approaches tailored to individual preferences have greater success. Packaging and disseminating physical activity programs for community, worksite, and health care settings are not as far along as for other areas, although inactivity prevalence is about twice that of smoking, and both risk factors have substantial morbidity and mortality. Less is known about effectiveness of upstream approaches, which have potential for the greatest public health impact. Suggestions include continued promotion of moderate-intensity physical activity, greater dissemination of successful programs, and investigation of physical environment influences.

Physical activity interventions using mass media, print media, and information technology.

INTRODUCTION: Media-based physical activity interventions include a variety of print, graphic, audiovisual, and broadcast media programs intended to influence behavior change. New information technology allows print to be delivered in personalized, interactive formats that may enhance efficacy. Media-based interventions have been shaped by conceptual models from health education, Social Cognitive Theory, the Transtheoretical Model, and Social Marketing frameworks. METHODS: We reviewed 28 studies of media-based interventions of which seven were mass media campaigns at the state or national level and the remaining 21 were delivered through health care, the workplace, or in the community. RESULTS: Recall of mass-media messages generally was high, but mass-media campaigns had very little impact on physical activity behavior. Interventions using print and/or telephone were effective in changing behavior in the short term. Studies in which there were more contacts and interventions tailored to the target audience were most effective. CONCLUSION: A key issue for research on media-based physical activity interventions is reaching socially disadvantaged groups for whom access, particularly to new forms of communication technology, may be limited. There is a clear need for controlled trials comparing different forms and intensities of media-based physical activity interventions. Controlled studies of personalized print, interactive computer-mediated programs, and web-based formats for program delivery also are needed. The integration of media-based methods into public and private sector service delivery has much potential for innovation.

Induction of tolerance via the respiratory mucosa.

Immunological tolerance is defined as a state of specific non-responsiveness to a particular antigen induced by previous exposure to that same antigen. The mucosal surfaces comprise the upper and lower respiratory tracts, the gastrointestinal tract and the urogenitary tract, and are a major site of antigenic challenge. The immune system associated with the mucosa has the extraordinary potential to discriminate between antigens that are harmless (e.g. inhaled and dietary antigens) and those that are associated with pathogens. Normally soluble proteins delivered through the mucosal surfaces do not elicit a strong systemic immune response but instead induce a transient local immune response that is replaced by long-term peripheral unresponsiveness this is termed mucosal tolerance. The phenomenon of oral tolerance is well established and considerable attention has focussed on defining the underlying mechanisms. However, only comparatively recently was the induction of tolerance via the respiratory mucosa described, and it is this form of mucosal tolerance which forms the basis of this review.

Nitric oxide causes the macroschizonts of Theileria annulata to disappear and host cells to become apoptotic.

The proliferation of Theileria annulata macroschizont-infected cell lines in vitro was significantly inhibited by nitric oxide (NO) generated by S-nitroso-N-acetyl-DL-penicillamine (SNAP). Incubation with SNAP caused the macroschizonts to disappear and host cells to become apoptotic. SNAP-derived NO also significantly inhibited the incorporation of tritiated thymidine by cultures of cells in which the schizonts had been induced to differentiate into merozoites by maintenance at 41 degrees C instead of 37 degrees C, the temperature used for culturing macroschizont-infected cells. These results point to NO as the mediator of macrophage anti-T. annulata activity and provide new evidence that the protective immune mechanisms which allow cattle to recover from primary infection and resist challenge may be attributed principally to the products of activated macrophages. These findings indicate that effective inactivated vaccines against T. annulata should include antigens able to stimulate the type of CD4+ T cell response which elicits macrophage activation and NO synthesis.

Efficacy of an individualized, motivationally-tailored physical activity intervention.

This study compared the efficacy of two low-cost interventions for physical activity adoption. Sedentary (N = 194) adults recruited through newspaper advertisements were randomized to receive either a motivationally-matched, individually-tailored intervention (IT) or a standard self-help intervention (ST). Assessments and interventions were delivered by repeated mailings at baseline, one, three, and six months. Participants were assessed regarding current physical activity behavior, motivational readiness to adopt regular physical activity, and psychological constructs associated with physical activity participation (e.g. self-efficacy, decisional balance). Repeated measures analyses of variance (ANOVAs) revealed significant increases in physical activity participation between baseline and six months for both groups with a significantly greater increase among IT participants. The IT group outperformed the ST group on all primary outcome measures: (a) minutes of physical activity per week, (b) reaching Centers for Disease Control and American College of Sports Medicine (CDC/ACSM) recommended minimum physical activity criteria, and (c) achieving the Action stage of motivational readiness for physical activity adoption. Both groups showed significant improvement between baseline and six months on the psychological constructs associated with physical activity adoption (e.g. self-efficacy), with no significant differences observed between the treatment groups. Utilizing computer expert systems and self-help manuals to provide individually-tailored, motivationally-matched interventions appears to be an effective, low-cost approach for enhancing physical activity participation in the community.