A national anti-doping education programme reduces doping susceptibility in British athletes.

The World Anti-Doping Agency's International Standard for Education instructs that national and international sport organisations evaluate their education programmes. We addressed this directive by examining the effectiveness of a national anti-doping programme. Athletes (N = 302, 41% female) completed measures of doping susceptibility, intention to use dietary supplements, Spirit of Sport and moral values, anti-doping knowledge and practice, and whistleblowing, prior-to and three-months after attending an anti-doping education programme. At three-month follow-up, athletes reported decreased doping susceptibility and intention to use dietary supplements coupled with increased importance of values, anti-doping knowledge, anti-doping practice and whistleblowing. Within-participant, moderated-mediation analyses revealed that programme-related changes in doping susceptibility were indirectly related to changes in intention to use dietary supplements, and, that this indirect relationship was moderated by moral values. These findings confirm the effectiveness of a national anti-doping education programme and highlight the contribution of dietary supplement use and personal values to changes in doping susceptibility.

Negative pressure wound therapy for initial management of giant omphalocele.

BACKGROUND: Current treatment of giant omphalocele includes "paint and wait" or placement of mesh or silo. These methods are associated with high complication rates. We propose negative pressure wound therapy as an alternative. METHODS: Patients born between 2009 and 2014 with giant omphalocele were included. Outcomes analyzed were duration of therapy, time to full enteral feeds, treatment related complications, wound surface area over time, type, and time to definitive closure. RESULTS: Eight patients were reviewed. The median duration of therapy was 68 days. Median time to full enteral feeds was 19 days. There were no treatment discontinuations or complications including sac ruptures, wound infections, or fistulas. Wound contraction stopped at 2 months or around 7 cm(2). All surviving patients underwent definitive closure. CONCLUSIONS: Negative pressure wound therapy is a safe and effective treatment for giant omphalocele that allows feeding, has a low complication rate, and is completed in 2 months.

Induced mild systemic inflammation is associated with impaired ability to improve cognitive task performance by practice.

Elevated inflammatory levels are linked to poorer cognition, but experimental confirmation is lacking. This report examined associations between cognitive performance and inflammation induced by exercise and vaccination. Thirty-six (exercise N = 18, vaccination N = 18) healthy males completed a paced auditory serial addition test (PASAT), which is a multifaceted measure of cognitive function. The task was completed in placebo and elevated inflammation states. Improvements in PASAT performance were related to inflammation. In the exercise study, IL-6 during the first PASAT negatively correlated with PASAT improvement (p = .022). In the vaccination study, increases in C-reactive protein between PASATs correlated with reduced PASAT improvement (p < .001). Inflammation was linked to reduced improvements in cognitive performance. Further research should identify the specific cognitive functions affects and the underlying mechanisms.

Vaccine-induced inflammation attenuates the vascular responses to mental stress.

Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male participants completed two stress sessions: an inflammation condition having received a typhoid vaccination and a control (non-inflamed) condition. Tumor necrosis factor-alpha and interleukin-6 (p's<.001) increased following vaccination, confirming modest increases in inflammation. Mental stress increased blood flow, blood pressure, heart rate, and cardiac output in both conditions (all p's<.001), but the blood flow response to stress was attenuated having received the vaccination compared to the control condition (p's<.05). These results further implicate the interaction between inflammation and the vasculature as a mechanism through which stress may trigger myocardial infarction.

The time course of the inflammatory response to the Salmonella typhi vaccination.

The Salmonella typhi vaccination induces transient increases in inflammatory-responsive cytokines and molecules. For instance, it causes small, mild increases in interleukin-6 (IL-6) within a few hours and C-reactive protein (CRP) within 24h. No study has charted either the time course of the inflammatory response to this vaccine or any associated changes in mood, physical symptoms, and cardiac function. In a blinded crossover experimental design, eight participants received the S. typhi vaccine (vaccination condition) and a saline (control condition) injection on two separate days, at least one week apart. Blood samples and mood ratings were collected at 0, 4, 5, 6, 7, 8 and 24h post-injection, physical symptoms and pain were assessed at 4-8 and 24h post-injection, and cardiovascular function was recorded until 8h post-injection. Repeated measures analyses of variance and polynomial trend analyses compared the timecourse of the response patterns between the two conditions. Whereas there were no temporal changes in the control condition, the vaccination increased granulocytes, IL-6, TNF-α, and CRP (all p's<.05). Specifically, the granulocytes, IL-6 and TNF-α peaked after 6-8h while CRP peaked after 24h. This vaccine-induced mild inflammatory response was not accompanied by any changes in mood or cardiovascular activity. We also found that participants tended to report more pain in the injected limb in the vaccination condition (p<.07). In sum, our study charted the timecourse of key inflammatory-responsive markers following S. typhi vaccination and identified the timing of their modest peaks. It is worth noting that changes in these markers were not accompanied by any notable changes in mood or cardiovascular activity, and thus the S. typhi vaccination is a suitable method to induce increases in inflammatory-responsive markers, without altering mood or cardiovascular parameters.

Cortical and autonomic responses to noxious stimulation during anesthesia in cardiac surgery patients are moderated by preanesthetic blood pressure levels.

Evidence has revealed that elevated blood pressure is associated with reduced sensitivity to noxious stimulation. The current study investigated the association between resting blood pressure and nociception during anesthesia in 32 patients undergoing cardiac surgery. Pain-related middle latency cortical somatosensory evoked potentials (MLCEPs) elicited by noxious 50 mA median nerve stimulation were used to assess intraoperative nociception and algesia. Noxious stimulation elicited MLCEPs in 18 (56%) patients. Resting blood pressure was significantly higher in patients without MLCEP than those with MLCEP. Moreover, systolic blood pressure responses to intraoperative electrical stimulation of median nerve were blunted in the group without MLCEP compared to those with MLCEP. The current findings extend the hypertensive hypoalgesia phenomenon to the operating theatre.

Adenoviral-mediated Cre expression effectively suppresses GlyT1 binding in the thalamic area of GlyT1 conditional knock-out mice.

To properly understand the function of genes of neurological interest, in vivo manipulation in the adult is essential, particularly when the target gene is involved in brain development. Moreover, since the physiological effects of target protein may be region-specific, targeting a distinct brain region could be required to dissect these effects in specific brain locations. Infection of somatic tissues of transgenic mice bearing loxP-flanked gene sequences with a viral vector expressing Cre recombinase provides a means of allowing flexible spatio-temporal control of target gene expression. Viral vector-mediated Cre expression could be used to mediate localized gene modulation in a specific brain region. In the present study this technology was applied to the glycine transporter type-1 (GlyT1) protein which is responsible for the uptake of synaptic glycine in the forebrain and has been implicated as a therapeutic target for the treatment of schizophrenia. Since GlyT1 is widely expressed in glial cells, we employed an adenoviral-based vector (Ad5) to deliver Cre protein, due to the preferentially transduction of glial cells by adenoviral vectors in rodent brain. We show significant reduced GlyT1 binding specifically in the thalamic area of conditional GlyT1 (GlyT1c) transgenic mice injected with Ad5-Cre virus, as measured by GlyT1 autoradiography. In conclusion, we demonstrated the validity of viral vector-mediated delivery of Cre to loxP targeted transgenic mice as a novel strategy to investigate target gene function in selected subregions of the adult brain, which provides a valuable technique to investigate gene function both in normal physiology and in disease models.

The effects of vaccine timing on the efficacy of an acute eccentric exercise intervention on the immune response to an influenza vaccine in young adults.

An acute bout of exercise prior to vaccination can improve the antibody and cell-mediated responses to influenza vaccination. The mechanisms underpinning this adjuvant effect remain unclear, and further investigation to determine the optimal exercise protocol is warranted. The aim of the current study was to determine whether exercise augmented the immune response to vaccination, and whether the timing of exercise relative to vaccination affected the efficacy of the intervention. One hundred and fifty-six (76 men) healthy participants were randomly assigned to a control group or one of three intervention groups who exercised immediately, 6h or 48 h prior to administration of a standard trivalent influenza vaccine. The exercise groups performed 50 repetitions of the eccentric portion of both the bicep curl and lateral raise movements at an intensity eliciting 85% of each participant's pre-determined concentric one repetition maxima. Antigen-specific serum antibody titres were measured at baseline and 28 days post-vaccination as indicators of the humoral response. All three viral strains elicited strong antibody responses; however, eccentric exercise did not further augment any antibody responses compared to the control group. Cell-mediated immunity at 28 days post-vaccination was determined by measuring the IFN-gamma response to in vitro stimulation of the blood with whole vaccine. There were no differences in cell-mediated immunity among the groups. Although these null findings were unexpected, they are consistent with previous research showing that exercise-induced immunoenhancement was only observed when the control group had relatively poor responses. In conclusion, it is likely that the robust immune responses to the vaccine observed in this study may have limited any further immune enhancement by exercise.

Effects of sex, phase of the menstrual cycle and gonadal hormones on pain in healthy humans.

Sex differences in pain have been noted; women typically report more pain than men. Gonadal hormones may influence pain reports, and, moreover, such hormones may help to explain sex differences and menstrual cycle differences in pain. This study measured venipuncture and intravenous catherization pain during the follicular and luteal phases of the menstrual cycle in regularly menstruating women. Pain was also assessed in a group of men. Pain ratings were higher in women than men. In women, pain ratings did not differ between the follicular and luteal phases. Estradiol and progesterone increased from follicular to luteal phases. Within-phase analyses revealed that pain ratings were positively correlated with estradiol and progesterone during the luteal phase. Moreover, increases in estradiol and progesterone across the menstrual cycle were positively correlated with increases in pain. These findings suggest that variations in gonadal hormones during the menstrual cycle influence the experience of pain in healthy women.

Sex differences in the interleukin-6 response to acute psychological stress.

Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory response, may mediate inflammatory disease exacerbation associated with stress. Twenty men and twenty women completed a single session, comprising baseline (20 min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken at baseline, immediately after the task, and at +30 and +60 min recovery were analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60 min recovery, and a sex difference was found in the IL-6 response, with men peaking earlier than women. These findings confirm a small delayed IL-6 increase after acute laboratory stress, and reveal sex differences in the profile of the IL-6 response.

Acute stress exposure prior to influenza vaccination enhances antibody response in women.

Animal studies have shown that an acute stressor in close temporal proximity to immune challenge can enhance the response to delayed-type hypersensitivity and antibody response to vaccination. The current study examined the effects of acute exercise or mental stress prior to influenza vaccination on the subsequent antibody response to each of the three viral strains. Sixty young healthy adults (31 men, 29 women) were randomly allocated to one of three task conditions: dynamic exercise, mental stress, or control. After an initial baseline, participants completed their allocated 45 min task and then received the influenza vaccine. Plasma cortisol and interleukin-6 were determined at the end of baseline, after the task, and after 60 min recovery. Antibody titres were measured pre-vaccination and at 4 weeks and 20 weeks post-vaccination follow-ups. For the A/Panama strain, women in both the exercise and mental stress conditions showed higher antibody titres at both 4 and 20 weeks than those in the control condition, while men responded similarly in all conditions. Interleukin-6 at +60 min recovery was found to be a significant predictor of subsequent A/Panama antibody response in women. In line with animal research, the current study provides preliminary evidence that acute stress can enhance the antibody response to vaccination in humans.

Cytolytic viruses as potential anti-cancer agents.

The resistance of cancers to conventional therapies has inspired the search for novel strategies. One such approach, namely gene therapy, is based upon the introduction of genes such as those encoding suicide proteins, tumour suppressor proteins or cytokines into tumour cells by means of a genetic vector. The efficiency with which viruses transfer their genes from one host cell to another has led to the widespread use of viruses as genetic vectors. For safety reasons, such virus vectors are generally replication-defective but, unfortunately, this has limited the efficacy of treatment by restricting the number of cells to which the therapeutic gene is delivered. For this reason, the use of replication-competent viruses has been proposed, since virus replication would be expected to lead to amplification and spread of the therapeutic genes in vivo. The replication of many viruses results in lysis of the host cells. This inherent cytotoxicity, together with the efficiency with which viruses can spread from one cell to another, has inspired the notion that replication-competent viruses could be exploited for cancer treatment. Some viruses have been shown to replicate more efficiently in transformed cells but it is unlikely that such examples will exhibit a high enough degree of tumour selectivity, and hence safety, for the treatment of patients. Our increasing knowledge of the pathogenesis of virus disease and the ability to manipulate specific regions of viral genomes have allowed the construction of viruses that are attenuated in normal cells but retain their ability to lyse tumour cells. Such manipulations have included modifying the ability of viruses to bind to, or replicate in, particular cell types, while others have involved the construction of replication-competent viruses encoding suicide proteins or cytokines. Naturally occurring or genetically engineered oncolytic viruses based upon adenovirus, herpes simplex virus, Newcastle disease virus, poliovirus, vesicular stomatitis virus, weasles virus and reovirus have been described. The results of animal studies are encouraging and a number of viruses are now being evaluated in clinical trials.