A gutsy performance: the potential for supplementation of short-chain fatty acids to benefit athletic health, exercise performance, and recovery.

The gut microbiome is known to play an important role in the day-to-day physiology and health of the human host. It is, therefore, not surprising that there is interest surrounding the gut microbiome and its potential to benefit athletic health and performance. This has, in part, been driven by the consideration that gut bacterial by-products (i.e. metabolic waste) could be harnessed by the host and utilised for a beneficial outcome. The concept of harnessing bacterial metabolites as beneficial health modulators has developed the theory of leveraging short-chain fatty acids (SCFAs) as novel supplements for enhancing athletic performance. This review discusses the current literature investigating SCFA administration in cellular, animal, and human models, with the aim of linking the demonstrated physiological/biochemical mechanisms to potential exercise/athletic benefit. In addition, practical implications and factors relating to SCFA-supplementation in athletic populations are considered. The literature demonstrates a tangible rationale that SCFAs can have a positive impact on human physiology to afford benefits to the athletic population. These advantages include the capacity to improve respiratory immunity to combat elevated levels/severity of upper respiratory tract infections often reported in athletes; the blunting of pro-inflammatory and pro-fibrotic pathways to aid in exercise recovery; and the role of SCFAs as usable energy sources and metabolism modulators to fuel exercise and improve performance and/or endurance capacity. However, there is currently minimal research completed in human participants and thus further investigations into the direct benefit of SCFAs in exercise performance and/or recovery-based studies are required.

A multi-site study on the impact of an advance care planning workshop on attitudes, beliefs and behavioural intentions over a 6-month period.

BACKGROUND: This study evaluated the impact of the adapted version of the Respecting Choices® The Living Matters Advance Care Planning (ACP) facilitator training programme on trainees' attitudes on facilitation 6 months post-training. SETTING AND PARTICIPANTS: Two hundred and twenty-one healthcare professionals consisting of doctors, nurses, medical social workers from different training venues in Singapore participated in the first phase of the study (pre- and post) of which 107 participated in the second phase 6 months later (follow-up). METHODS: Participants self-rated their attitudes, beliefs and behavioural intentions through surveys at three time points in an evaluation design that utilised repeated measures one-way ANOVA (pre-, post-, follow-up). Between-group differences were also examined using independent t-test. RESULTS: At follow-up, mean scores increased significantly in understanding, confidence, and competence. Changes in effect sizes were large. Although trainees continued to think that ACP is emotionally draining for facilitators, more than before, facilitation experience was considered pleasant for themselves with the positive change significant and moderate in effect size. Those who had experience completing/initiating ACP significantly held more positive views than those who did not. CONCLUSIONS: The ACP facilitator training programme had lasting effects on enhancing the understanding, competence, and confidence of trainees. Importantly, findings showed that experience in actual facilitation within 6 months after training was important and giving trainees opportunities to facilitate is recommended.

Low birth weight associates with hippocampal gene expression.

Birth weight predicts the lifetime risk for psychopathology suggesting that the quality of fetal development influences the predisposition for mental disorders. The connectivity and synaptic network of the hippocampus are implicated in depression, schizophrenia and anxiety. We thus examined the underlying molecular adaptations in the hippocampus as a function of the fetal conditions associated with low birth weight. We used tissues from the non-human primate, Macaca fascicularis, to identify changes in hippocampal gene expression early in postnatal development associated with naturally occurring low compared with normal birth weight. Microarrays were used to analyze gene expression and DNA methylation in the hippocampus of five low- and five normal-birth weight neonates. Real-time PCR was employed to validate differentially expressed genes. Birth weight associated with altered global transcription in the hippocampus. Hierarchical clustering of gene expression profiles from 24,154 probe sets grouped all samples except one by their birth weight status. Differentially expressed genes were enriched in biological processes associated with neuronal projection, positive regulation of transcription and apoptosis. About 4% of the genes with differential expression co-varied with DNA methylation levels. The data suggest that low birth weight is closely associated with hippocampal gene expression with a small epigenetic underpinning by DNA methylation in neonates. The data also provide a potential molecular basis for the developmental origin of an enhanced risk for mental disorders.

Measuring epigenetics as the mediator of gene/environment interactions in DOHaD.

Analysis of DNA methylation data in epigenome-wide association studies provides many bioinformatics and statistical challenges. Not least of these, are the non-independence of individual DNA methylation marks from each other, from genotype and from technical sources of variation. In this review we discuss DNA methylation data from the Infinium450K array and processing methodologies to reduce technical variation. We describe recent approaches to harness the concordance of neighbouring DNA methylation values to improve power in association studies. We also describe how the non-independence of genotype and DNA methylation has been used to infer causality (in the case of Mendelian randomization approaches); suggest the mediating effect of DNA methylation in linking intergenic single nucleotide polymorphisms, identified in genome-wide association studies, to phenotype; and to uncover the widespread influence of gene and environment interactions on methylation levels.

Satisfaction with sex and erection hardness: results of the Asia-Pacific sexual health and overall wellness survey.

The Asia-Pacific Sexual Health and Overall Wellness (AP SHOW) survey assessed sexual satisfaction and health and the association with erection hardness in 13 Asia-Pacific countries/regions. Adults aged 25-74 years who had sexual intercourse > 1 time in the past 12 months answered Internet surveys or participated in street-intercept interviews. Data were weighted by demographics and country/region size. Of 3957 (men, n=2016 and women, n=1941) respondents, 41% of men and 34% of women were completely or very satisfied with sex. Satisfaction with sex was linked to satisfaction with life priorities and overall health. Few respondents (men, 38% and women, 26%) were very or completely satisfied with erection hardness. Optimal erection hardness was reported by 45% of men (48% of women regarding their partners' erections). Erection hardness was associated with increased frequency of sex and importance of and satisfaction with erection-related elements of men's sexual performance. Approximately half of respondents (men, 57% and women, 47%) were at least moderately interested in improving the sexual experience. Most Asia-Pacific respondents were less than very satisfied with sex. Satisfaction with sex was associated with satisfaction with life priorities. Erection hardness was associated with sexual satisfaction and activity, satisfaction with life priorities and overall health.

A global bioheat model with self-tuning optimal regulation of body temperature using Hebbian feedback covariance learning.

In the lower brain, body temperature is continually being regulated almost flawlessly despite huge fluctuations in ambient and physiological conditions that constantly threaten the well-being of the body. The underlying control problem defining thermal homeostasis is one of great enormity: Many systems and sub-systems are involved in temperature regulation and physiological processes are intrinsically complex and intertwined. Thus the defining control system has to take into account the complications of nonlinearities, system uncertainties, delayed feedback loops as well as internal and external disturbances. In this paper, we propose a self-tuning adaptive thermal controller based upon Hebbian feedback covariance learning where the system is to be regulated continually to best suit its environment. This hypothesis is supported in part by postulations of the presence of adaptive optimization behavior in biological systems of certain organisms which face limited resources vital for survival. We demonstrate the use of Hebbian feedback covariance learning as a possible self-adaptive controller in body temperature regulation. The model postulates an important role of Hebbian covariance adaptation as a means of reinforcement learning in the thermal controller. The passive system is based on a simplified 2-node core and shell representation of the body, where global responses are captured. Model predictions are consistent with observed thermoregulatory responses to conditions of exercise and rest, and heat and cold stress. An important implication of the model is that optimal physiological behaviors arising from self-tuning adaptive regulation in the thermal controller may be responsible for the departure from homeostasis in abnormal states, e.g., fever. This was previously unexplained using the conventional "set-point" control theory.

Sequential VATS lung volume reduction surgery: prolongation of benefits derived after the initial operation.

OBJECTIVE: Sequential lung volume reduction (LVR) is thought to provide additional and prolonged benefit compared with unilateral LVR. We tested this hypothesis by reviewing physiological, subjective and survival outcome data on patients who underwent sequential or unilateral LVR. METHODS: LVR was performed as a unilateral video-assisted thoracoscopic surgery (VATS) procedure, with bilateral reduction being undertaken in a staged manner. Pulmonary function data were collected prospectively. A telephone survey of patients and general practitioners was used to determine quality of life and survival. RESULTS: Fifty patients underwent LVR. Twenty-one patients had staged reduction of the contra-lateral lung at a median interval of 9 months. Pre-operatively, patients undergoing sequential LVR were not significantly different from patients undergoing unilateral LVR: forced expiratory volume in 1 s (FEV1) 23% predicted vs. 27% predicted, KCO 40% vs. 45%, total lung capacity (TLC) 124% vs. 121%, residual volume (RV) 217% vs. 214%, health score 34.5 vs. 30.8. After single-side LVR, both groups demonstrated equivalent and significant improvement in spirometric and subjective health scores: FEV1 +15% predicted (P<0.01), TLC -5% (P=0.03), health score +80% (P<0.01). Patients undergoing sequential reduction demonstrated no further significant improvements using either an intragroup comparison with their pre-second operation values or an intergroup comparison with the unilateral LVR patients. However, sequential LVR appeared to prolong the benefits experienced after the initial surgery by 1 year. Overall, 12 patients (24%) died during follow-up with no survival difference between the two groups (P=0.65). CONCLUSION: Sequential LVR is a safe strategy. Undertaking LVR to the second side does not further improve spirometric or subjective performance but does prolong the benefits achieved with the initial reduction.

Non-invasive cardiac assessment in beta-thalassaemia major.

Iron deposition in the heart occurs in beta-thalassaemia major and contributes to cardiac dysfunction. Eighteen patients with beta-thalassaemia major were assessed clinically and had non-invasive investigations. They were young (15.5 +/- 3.6 years). Two patients had clinical heart failure. Doppler echocardiography demonstrated higher transmitral peak flow velocity in early and late diastole compared with controls (e: p<0.05, a: p<0.01). Transtricuspid peak late diastolic flow velocity was higher in patients (p<0.005). Isovolumic relaxation time was shortened (p<0.001). Pulmonary venous flow velocity was higher in diastole than systole (S: 0.51 +/- 0.11 m/s, D: 0.62 +/- 0.08 m/s). Reversal of pulmonary venous flow during atrial systole was seen in eight patients. These diastolic filling abnormalities did not significantly change with blood transfusion. Left ventricular ejection fraction was normal in patients. Two patients had cardiomegaly on chest X-ray. In beta-thalassaemia with iron overload, there is a restrictive pattern of diastolic dysfunction. This is not altered by recent blood transfusion. Left ventricular function remains relatively intact.

The first frozen embryo donation pregnancy for hypergonadotrophic hypogonadism in Singapore--hormonal profile and obstetric outcome.

This is the first report in South East Asia of a singleton frozen embryo donation pregnancy for hypergonadotrophic hypogonadism. The hormonal profile was compared with that of a control group of normal uncomplicated singleton pregnancies in Singapore. The plasma beta hCG levels were lower compared to those of our normal uncomplicated singleton pregnancies at 2 to 3 weeks after the embryo transfer but became comparable at 4 to 5 weeks after embryo transfer. The successful vaginal delivery and the obstetric complications developed in this case are discussed.

Endocarditis of the tricuspid valve associated with congenital coronary arteriovenous fistula.

A 17 year old girl with a congenital right coronary artery to coronary sinus fistula presented with recurrent septic pulmonary embolism secondary to tricuspid valve endocarditis. The diagnosis was made on the basis of echocardiography and cardiac angiography.

Once daily felodipine monotherapy in mild to moderate hypertension.

In a single-blind study conducted at our centres, 78 hypertensive patients were enrolled with 58 completing the study according to the protocol. Mean supine and standing blood pressures were significantly reduced after treatment with felodipine, reductions being 27/21 mmHg (p < 0.0001) and 25/19 mmHg (p < 0.0001) respectively. Of 46 patients given felodipine 5 mg, 44 (95.7%) achieved target blood pressure defined as a diastolic blood pressure of < 90 mmHg, while all 12 patients on felodipine 10 mg did so. The 2 patients who did not achieve target pressure at the final visit did so on previous visits. There were no differences in pre and post-treatment laboratory variables. Treatment was discontinued in 6 patients because of headaches. No adverse events of clinical significance were reported in the 58 patients who completed the study. In conclusion, we found felodipine given once daily to be effective in the treatment of mild to moderate hypertension.

Cardiac abnormalities in systemic lupus erythematosus: prevalence and relationship to disease activity.

We conducted a prospective longitudinal study to determine the nature and prevalence of cardiac abnormalities in systemic lupus erythematosus and to study their natural history and relationship with disease activity. Forty consecutive inpatients with systemic lupus erythematosus were studied during their admission and subsequently 6 to 12 months later. On each occasion a clinical cardiovascular examination was carried out, disease activity was scored using the "Lupus Activity Criteria Count" and a Doppler echocardiographic examination was carried out. 72.5% of patients had an abnormal echocardiogram in the first study while 51.7% were abnormal during the follow-up study. Valvar disease occurred in 37.5% of patients. The mitral valve was most commonly affected. Libman-Sacks endocarditis was rare (2.5%). Pericardial effusions were seen in 36.2% of echocardiograms. The majority (76.0%) of these were associated with hypoalbuminaemia. 80.0% of patients had active disease during the first examination and 41.4% at follow-up. There was no correlation between activity of disease and prevalence of cardiac abnormalities at either examination. We conclude that cardiac disease is common in systemic lupus erythematosus. Prevalence of cardiac abnormality did not correlate with disease activity.

Regulation of noradrenaline release from rat occipital cortex tissue chops by alpha 2-adrenergic agonists.

Noradrenaline (NA) and the alpha 2-adrenergic agonists clonidine, BHT-920, and UK 14304-18 inhibit potassium-evoked release of [3H]NA from rat occipital cortex tissue chops with similar potencies. NA (10(-5) M) was most effective as up to 85% inhibition could be observed compared with 75%, 55%, and 35% for UK 14304-18, clonidine, and BHT-920, respectively, all at 10(-5) M. Potassium-evoked release was enhanced by both forskolin (10(-5) M) and 1 mM dibutyryl cyclic AMP. Pretreatment of tissue chops with 1 mM dibutyryl cyclic AMP in the presence of 3-isobutyl-1-methylxanthine partially reversed the alpha 2-adrenergic agonist inhibition of NA release. No reversal of inhibition was observed following pretreatment with 10(-5) M forskolin. The effects of clonidine, BHT-920, UK-14308-18, and NA on cyclic AMP formation stimulated by (a) forskolin, (b) isoprenaline, (c) adenosine, (d) potassium, and (e) NA were examined. Only cAMP formation stimulated by NA was inhibited by these alpha 2-adrenergic agonists. These results suggest that only a small fraction of adenylate cyclase in rat occipital cortex is coupled to alpha 2-adrenergic receptors. These results are discussed in relation to recent findings that several alpha 2-adrenergic receptor subtypes occur, not all of which are coupled to the inhibition of adenylate cyclase, and that alpha 2-adrenergic receptors inhibit NA release in rat occipital cortex by a mechanism that does not involve decreasing cyclic AMP levels.

The lack of relationship between acetylator phenotype and idiopathic systemic lupus erythematosus in a South-east Asian population: a study of Indians, Malays and Malaysian Chinese.

An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators. The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia. The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively. This did not differ significantly from the respective healthy groups (20 and 29%). The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status.

Paraquat poisoning: per vagina.

We describe a fatal case of paraquat poisoning as a result of per vaginal contact with the herbicide. Death occurred 18 days later from hepatic, renal and respiratory failure.

Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina.

Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once-daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients.

Plasma flecainide concentrations following acute myocardial infarction.

Plasma flecainide concentrations were measured in 10 patients with acute myocardial infarction. Following an oral loading dose of 300 mg plasma concentrations were highly variable and unpredictable. Subsequently, doses of 150 mg twice daily produced mean plasma flecainide concentrations consistently above 400 micrograms/1 within 48 hours. Oral flecainide is, therefore, subject to the same problems of varying oral bioavailability as other antiarrhythmic drugs tested following acute myocardial infarction and, initially, an intravenous regime remains preferable. Mild pulmonary oedema occurred in six patients and, although it responded to one dose of frusemide and did not recur, flecainide must be used with caution when significant left ventricular dysfunction is suspected.

Alteration of lymphocyte reactivities by thyroid hormones.

The effects of thyroid hormones (L-T4, L-T3 and rT3) on the proliferative response of rabbit peripheral blood lymphocytes to T-cell mitogens, PHA and Con A, and B cell specific goat anti-rabbit light chain antibodies (Anti-L) were investigated. It was observed that L-T4 potentiated the lymphocyte response to mitogens and Anti-L in a dose-dependent manner: 10(-9) M and 10(-8) M had no effect while 10(-7)-10(-5) M significantly enhanced the lymphocyte response. L-T3 (10(-11)-10(-8) M) had no effect on the lymphocyte response to PHA and Con A. At 10(-7) M, L-T3 inhibited the response to PHA but not Con A. L-T3 (10(-11)-10(-7) M) suppressed the lymphocyte response to Anti-L. The suppression was directly proportional to the L-T3 concentration. rT3 (10(-11)-10(-7) M) inhibited the proliferative response to PHA and Anti-L in a dose-related manner. Its effect on the lymphocyte response to Con A was stimulatory at 10(-11) M but inhibitory at higher concentrations (10(-8) and 10(-7) M). rT3 suppressed the enhancement by L-T4 of the lymphocyte response to the mitogens and Anti-L. The degree of suppression was proportional to its concentration. This data indicated that thyroid hormones can alter the reactivities of lymphocytes. The direction and magnitude of the alteration appear to depend on the concentration of a specific thyroid hormone encountered by the responding cells.