Reduced auditory steady state responses in autism spectrum disorder.

BACKGROUND: Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192-197). METHODS: Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. RESULTS: The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. LIMITATIONS: In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. CONCLUSION: Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

Oscillatory networks of high-level mental alignment: A perspective-taking MEG study.

Mentally imagining another's perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al. (2016) showed that theta-band (3-7 Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a similar paradigm, we set out to unravel the extended functional brain network in detail. Increasing the angle between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral prefrontal cortex (PFC) and right anterior cingulate cortex (ACC). Using Granger-causality, we showed that lateral PFC and ACC exert top-down influence over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling in relation to the rTPJ. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a 'hub' to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations.

The effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D: a prospective randomised trial.

AIMS: To evaluate the effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D and a long bone fracture. PATIENTS AND METHODS: Between July 2011 and August 2013, 113 adults with a long bone fracture were enrolled in a prospective randomised double-blind placebo-controlled trial. Their serum vitamin D levels were measured and a total of 100 patients were found to be vitamin D deficient (< 20 ng/ml) or insufficient (< 30 ng/mL). These were then randomised to receive a single dose of vitamin D3 orally (100 000 IU) within two weeks of injury (treatment group, n = 50) or a placebo (control group, n = 50). We recorded patient demographics, fracture location and treatment, vitamin D level, time to fracture union and complications, including vitamin D toxicity. Outcomes included union, nonunion or complication requiring an early, unplanned secondary procedure. Patients without an outcome at 15 months and no scheduled follow-up were considered lost to follow-up. The t-test and cross tabulations verified the adequacy of randomisation. An intention-to-treat analysis was carried out. RESULTS: In all, 100 (89%) patients had hypovitaminosis D. Both treatment and control groups had similar demographics and injury characteristics. The initial median vitamin D levels were 16 ng/mL (interquartile range 5 to 28) in both groups (p = 0.885). A total of 14 patients were lost to follow-up (seven from each group), two had fixation failure (one in each group) and one control group patient developed an infection. Overall, the nonunion rate was 4% (two per group). No patient showed signs of clinical toxicity from their supplement. CONCLUSIONS: Despite finding a high level of hypovitaminosis D, the rate of union was high and independent of supplementation with vitamin D3. Cite this article: Bone Joint J 2017;99-B:1520-5.

Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling.

Although atypical social behaviour remains a key characterisation of ASD, the presence of sensory and perceptual abnormalities has been given a more central role in recent classification changes. An understanding of the origins of such aberrations could thus prove a fruitful focus for ASD research. Early neurocognitive models of ASD suggested that the study of high frequency activity in the brain as a measure of cortical connectivity might provide the key to understanding the neural correlates of sensory and perceptual deviations in ASD. As our review shows, the findings from subsequent research have been inconsistent, with a lack of agreement about the nature of any high frequency disturbances in ASD brains. Based on the application of new techniques using more sophisticated measures of brain synchronisation, direction of information flow, and invoking the coupling between high and low frequency bands, we propose a framework which could reconcile apparently conflicting findings in this area and would be consistent both with emerging neurocognitive models of autism and with the heterogeneity of the condition.

Coccygectomy for patients with chronic coccydynia: a prospective, observational study of 98 patients.

AIMS: The purpose of this prospective study was to evaluate the outcomes of coccygectomy for patients with chronic coccydynia. PATIENTS AND METHODS: Between 2007 and 2011, 98 patients underwent coccygectomy for chronic coccydynia. The patients were aged > 18 years, had coccygeal pain, local tenderness and a radiological abnormality, and had failed conservative management. Outcome measures were the Short Form 36 (SF-36), the Oswestry Disability Index (ODI) and a visual analogue scale (VAS) for pain. Secondary analysis compared the pre-operative features and the outcomes of patients with successful and failed treatment, two years post-operatively. The threshold for success was based on a minimum clinically important difference (MCID) on the ODI of 20 points. All other patients, including those lost to follow-up, were classified as failures. RESULTS: There was significant improvement in all ten components of the SF-36 (p < 0.05), the ODI (23 points) and VAS (39 points) (p < 0.0001). A total of 69 patients (70.4%) met the designated MCID threshold for a successful outcome. The failure group consisted of 25 patients (25.5%) who did not reach the MCID and four (4.1%) who were lost to follow-up. Six patients (6.1%) in the failure group had ODI scores that were no better or worse than that pre-operatively. The patients in whom treatment failed had significantly worse pre-operative scores for the ODI (p = 0.04), VAS (p = 0.02) and on five of ten SF-36 components (p < 0.04). They also had a higher incidence of psychiatric disorders, pre-operative opiate use and more than three comorbidities. TAKE HOME MESSAGE: Coccygectomy for chronic coccydynia results in significant improvement in patient-reported outcomes at two years. Failure is associated with certain pre-operative characteristics such as psychiatric illness, poor quality of life features, higher levels of pain, and use of opiates.

Mate choice among yeast gametes can purge deleterious mutations.

Meiosis in Saccharomyces yeast produces four haploid gametes that usually fuse with each other, an extreme form of self-fertilization among the products of a single meiosis known as automixis. The gametes signal to each other with sex pheromone. Better-quality gametes produce stronger signals and are preferred as mates. We suggest that the function of this signalling system is to enable mate choice among the four gametes from a single meiosis and so to promote the clearance of deleterious mutations. To support this claim, we construct a mathematical model that shows that signalling during automixis (i) improves the long-term fitness of a yeast colony and (ii) lowers its mutational load. We also show that the benefit to signalling is greater with larger numbers of segregating mutations.

A composite computational model of liver glucose homeostasis. II. Exploring system behaviour.

Using a composite model of the glucose homeostasis system, consisting of seven interconnected submodels, we enumerate the possible behaviours of the model in response to variation of liver insulin sensitivity and dietary glucose variability. The model can reproduce published experimental manipulations of the glucose homeostasis system and clearly illustrates several important properties of glucose homeostasis-boundedness in model parameters of the region of efficient homeostasis, existence of an insulin sensitivity that allows effective homeostatic control and the importance of transient and oscillatory behaviour in characterizing homeostatic failure. Bifurcation analysis shows that the appearance of a stable limit cycle can be identified.

A composite computational model of liver glucose homeostasis. I. Building the composite model.

A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an 'engineering' approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.

Are alcohol containing mouthwashes safe?

Alcohol (ethanol) is a constituent of many proprietary mouthwashes. Some studies have shown that regular use of such mouthwashes can increase the risk of developing oral cancer. Recently, the evidence has been reviewed by two separate authors. The conclusions from these reviews are conflicting. In this paper, we reconsider the epidemiological evidence linking alcohol containing mouthwashes with an increased risk of oral cancer. The evidence is considered in term of sample size, strength of association, confounding variables and data collection. In addition, clinical studies comparing alcohol versus non-alcohol mouthwashes are evaluated. The evidence suggests that the alcohol component of mouthwashes affords little additional benefit to the other active ingredients in terms of plaque and gingivitis control. In view of this outcome and the hypothetical risk of oral cancer, it would seem prudent that members of the dental team advise their patients accordingly.

Is gum disease killing your patient?

There is considerable epidemiological evidence to support the concept that poor oral health, especially the extent and severity of periodontal disease, may put patients at a significant risk for a variety of systemic conditions. This association raises the question that if patients or members of the dental profession ignore oral health, is there an increased risk of morbidity and mortality? In this presentation, the relationship between periodontal disease and many systemic conditions will be explored further. In addition, if periodontal disease does increase the risk of various systemic diseases, it raises the issue as to what the impact of treating periodontal disease is in reducing the magnitude of the risk. There is increasing evidence that reducing the inflammatory component in the periodontal tissues does have potential systemic effects. This has been shown to improve hyperglycaemic control in diabetics, reduce the prevalence of adverse pregnancy outcomes and improve surrogate markers that may be of benefit in patients suffering from coronary heart disease.

The efficacy of topical hyaluronic acid in the management of oral lichen planus.

BACKGROUND: The aim of this study was to evaluate the efficacy of a topical hyaluronic acid (HA) gel preparation (0.2%) in the management of oral lichen planus (OLP). METHODS: A total of 124 patients with erosive OLP participated in a randomized, placebo-controlled, double-blind trial to evaluate the efficacy of a topical HA preparation. Outcome measures included soreness relief following immediate application, oral function and size of erosive/ulcerative area. Patients were medicated for 28 days and completed a log diary recording oral function and soreness scores. RESULTS: Application of topical HA produced a significant reduction (P < 0.05) in soreness scores when compared with placebo for up to 4 h post-application. There was no difference between treatment groups (P > 0.05) with respect to oral function. Patients treated with 0.2% HA showed a significant reduction (P < 0.05) in the size of the erosive/ulcerated area after 28 days of treatment when compared with baseline. There was no significant difference in changes in ulcerative areas between treatment groups. CONCLUSIONS: Topical HA (0.2%) does appear to be of some benefit in the management of erosive lichen planus providing efficacy for up to 4 h after administration. Very frequent applications should be considered to obtain a more significant clinical benefit. Topical HA gel may be a useful addition to the treatment option for OLP.

Postprandial metabolic increment of southern bluefin tuna Thunnus maccoyii ingesting high or low-lipid sardines Sardinops sagax.

This study examined the postprandial metabolism and swimming speed of southern bluefin tuna Thunnus maccoyii when fed sardines Sardinops sagax of either high-lipid and high-energy content or low-lipid and low-energy content. Five groups of two or three T. maccoyii (mean+/-s.e. mass=19.8+/-0.5 kg, n=14) were fed either low [2.2% lipid, 5.5 MJ kg(-1) gross energy (GE)] or high-lipid (12.9%, 9.2 MJ kg(-1) GE) S. sagax. Before feeding, T. maccoyii swam at 0.74+/-0.03 body lengths s(-1) (n=5) and their routine metabolic rate was 305+/-15 mg kg(-1) h(-1). Swimming speed and metabolic rate of T. maccoyii increased following feeding. Thunnus maccoyii swam 1.3 and 1.8 times faster during digestion of low and high-lipid S. sagax, respectively. Postprandial peak metabolic rate, duration of elevated metabolism and total postprandial metabolic increment were all greater for T. maccoyii that ingested high-lipid S. sagax. When total postprandial increment is represented as a proportion of ingested energy, there was no difference between high and low-lipid meals, equating to between 30 and 35% of ingested energy. It was estimated that increased postprandial swimming costs account for 25 and 46% of the total postprandial metabolic response for low and high-lipid S. sagax meals, respectively. Specific dynamic action (SDA) accounts for c. 20% of ingested energy regardless of S. sagax lipid level. These results confirm that the postprandial metabolic increment of T. maccoyii is greater than most other fish species. Much of the high cost of postprandial metabolic increment can be attributed to increased postprandial swimming costs. For T. maccoyii, it appears that activity and SDA are not independent, which complicates bioenergetic evaluation. High postprandial metabolic costs accentuate the great energetic requirements of T. maccoyii.

Moving with the beat: heart rate and visceral temperature of free-swimming and feeding bluefin tuna.

Owing to the inherent difficulties of studying bluefin tuna, nothing is known of the cardiovascular function of free-swimming fish. Here, we surgically implanted newly designed data loggers into the visceral cavity of juvenile southern bluefin tuna (Thunnus maccoyii) to measure changes in the heart rate (fH) and visceral temperature (TV) during a two-week feeding regime in sea pens at Port Lincoln, Australia. Fish ranged in body mass from 10 to 21 kg, and water temperature remained at 18-19 degrees C. Pre-feeding fH typically ranged from 20 to 50 beats min(-1). Each feeding bout (meal sizes 2-7% of tuna body mass) was characterized by increased levels of activity and fH (up to 130 beats min(-1)), and a decrease in TV from approximately 20 to 18 degrees C as cold sardines were consumed. The feeding bout was promptly followed by a rapid increase in TV, which signified the beginning of the heat increment of feeding (HIF). The time interval between meal consumption and the completion of HIF ranged from 10 to 24 hours and was strongly correlated with ration size. Although fH generally decreased after its peak during the feeding bout, it remained elevated during the digestive period and returned to routine levels on a similar, but slightly earlier, temporal scale to TV. These data imply a large contribution of fH to the increase in circulatory oxygen transport that is required for digestion. Furthermore, these data oppose the contention that maximum fH is exceptional in bluefin tuna compared with other fishes, and so it is likely that enhanced cardiac stroke volume and blood oxygen carrying capacity are the principal factors allowing superior rates of circulatory oxygen transport in tuna.

Thermal effects on the blood respiratory properties of southern bluefin tuna, Thunnus maccoyii.

Thermal effects on the blood respiratory properties of southern bluefin tuna (Thunnus maccoyii) at 10, 23 and 36 degrees C, and at 0.5 and 1.5% CO(2) were investigated. A reversed temperature effect occurred as the oxygen partial pressure required for 50% haemoglobin saturation (P(50)) at 0.5% CO(2) decreased from 2.9 kPa at 10 degrees C to 1.7 kPa at 23 degrees C (apparent heat of oxygenation, DeltaH degrees , =+27 kJ mol(-1)). However, oxygen binding was essentially independent of temperature at warmer temperatures (P(50)=1.7-2.0 kPa from 23-36 degrees C at 0.5% CO(2); DeltaH degrees =-6.5 kJ mol(-1)). Hill's coefficient (n(H)) ranged from 1.3 to 1.6, and there was a large effect of temperature on the Bohr factor (DeltalogP(50)/DeltapH=-1.6 at 10 degrees C and -0.9 at 36 degrees C). This is the first study of whole blood to demonstrate the thermal dependence of DeltaH degrees itself, whereby the oxygen equilibrium curve is more sensitive to temperature in the lowest thermal range examined. We suggest that the functional basis for these observations lies in the necessity to ensure a sufficient oxygen supply to all tissues, including the heart and liver, without suffering from premature or excessive oxygen unloading around the heat exchanger prior to delivery of oxygen to organs and tissues that lie efferent to the exchanger.

In vivo time-resolved autofluorescence measurements to test for glycation of human skin.

We present an evaluation of time-resolved fluorescence measurements on human skin for screening type 2 diabetes. In vivo human skin is excited with a pulse diode at 375 nm and pulse width of 700 ps. Fluorescence decays are recorded at four different emission wavelengths: 442, 460, 478, and 496 nm. Experiments are performed at various locations, including the palms, arms, legs, and cheeks of a healthy Caucasian subject to test single-subject variability. The fluorescence decays obtained are modeled using a three-exponential decay. The variations in the lifetimes and amplitudes from one location to another are minimal, except on the cheek. We compare the fluorescent decays of 38 diabetic subjects and 37 nondiabetic subjects, with different skin complexions and of ages ranging from 6 to 85 yr. The average lifetimes for nondiabetic subjects were 0.5, 2.6, and 9.2 ns with fractional amplitudes of 0.78, 0.18, and 0.03, respectively. The effects of average hemoglobin A1c (HbA1c) from the previous 4 yr and diabetes duration are evaluated. While no significant differences between the fluorescence lifetimes of nondiabetic and diabetic subjects are observed, two of the fractional amplitudes are statistically different. Additionally, none of the six fluorescence parameters correlated with diabetes duration or HbA1c. One of the lifetimes as well as two of the fractional amplitudes differ between diabetic subjects with foot ulcers and nondiabetic subjects.

Routine metabolic rate of southern bluefin tuna (Thunnus maccoyii).

Routine metabolic rate (RMR) was measured in fasting southern bluefin tuna, Thunnus maccoyii, the largest tuna species studied so far (body mass=19.6 kg (+/-1.9 SE)). Mean mass-specific RMR was 460 mg kg(-1) h(-1) (+/-34.9) at a mean water temperature of 19 degrees C. When evaluated southern bluefin tuna standard metabolic rate (SMR) is added to published values of other tuna species, there is a strong allometeric relationship with body mass (423 M(0.86), R(2)=0.97). This demonstrates that tuna interspecific SMR scale with respect to body mass similar to that of other active teleosts, but is approximately 4-fold higher. However, RMR (not SMR) is most appropriate in ram-ventilating species that are physiologically unable to achieve complete rest. Respiration was measured in a large (250,000 l) flexible polypropylene respirometer (mesocosm respirometer) that was deployed within a marine-farm sea cage for 29 days. Fasted fish were maintained within the respirometer up to 42 h while dissolved oxygen dropped by 0.056 (+/-0.004) mg l(-1) h(-1). Fish showed no obvious signs of stress. They swam at 1.1 (+/-0.1) fork lengths per second and several fed within the respirometer immediately after measurements.

Human diseases - the Newcastle experience.

The second edition of The first five years, published by the General Dental Council in 2002, identifies human diseases as a specific subject to be taught as part of the BDS curriculum. It states clearly the particular learning outcomes of such a course and then identifies a range of subjects (pathology, microbiology, medicine, surgery, pharmacology, therapeutics, accident and emergency services and medical emergencies) which should constitute the programme. Previously, many of these topics were taught and examined separately. In this article, we would like to share the Newcastle experience of developing a course in human diseases alongside the GDC guidelines.

Gingival fibroblasts grown from cyclosporin-treated patients show a reduced production of matrix metalloproteinase-1 (MMP-1) compared with normal gingival fibroblasts, and cyclosporin down-regulates the production of MMP-1 stimulated by pro-inflammatory cytokines.

BACKGROUND AND OBJECTIVE: Cyclosporin-induced gingival overgrowth arises from an alteration in collagen homeostasis and is enhanced by inflammatory changes in the gingival tissues. The aim of this study was to investigate the interaction among interleukin-1, oncostatin M, cyclosporin and nifedipine in promoting the up-regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase by gingival fibroblasts. MATERIAL AND METHODS: Fibroblast cultures (n = 5) were obtained from healthy controls and from patients with cyclosporin-induced gingival overgrowth, and cells were harvested between the fourth and ninth passages. Cells were stimulated with interleukin-1 and oncostatin M, alone or in combination, and with different concentrations of cyclosporin (0-2000 ng/mL) and nifedipine (0-200 ng/mL). MMP-1 and tissue inhibitor of metalloproteinase-1 production was determined using an enzyme-linked immunosorbent assay technique. A CyQuant cell proliferation assay was used to determine the DNA concentration in the sample. RESULTS: Fibroblasts obtained from patients with cyclosporin-induced gingival overgrowth produced significantly lower levels of MMP-1 than control fibroblasts (p < 0.001); tissue inhibitor of metalloproteinase-1 levels were significantly lower (p < 0.05), and the ratio of MMP-1 to tissue inhibitor of metalloproteinase-1 was reduced, in the conditioned medium of patients with cyclosporin-induced gingival overgrowth compared with controls. Interleukin-1 and oncostatin M produced a significant increase in the up-regulation of MMP-1, which was reversed when cyclosporin and nifedipine were added to the cell cultures (p < 0.05). CONCLUSION: Pro-inflammatory cytokines significantly up-regulate MMP-1 in cultured gingival fibroblasts. Up-regulation is attenuated by both cyclosporin and nifedipine. The interaction may account for the synergism between inflammation and cyclosporin-induced gingival overgrowth.

Changes in cardiac output during swimming and aquatic hypoxia in the air-breathing Pacific tarpon.

Pacific tarpon (Megalops cyprinoides) use a modified gas bladder as an air-breathing organ (ABO). We examined changes in cardiac output (V(b)) associated with increases in air-breathing that accompany exercise and aquatic hypoxia. Juvenile (0.49 kg) and adult (1.21 kg) tarpon were allowed to recover in a swim flume at 27 degrees C after being instrumented with a Doppler flow probe around the ventral aorta to monitor V(b) and with a fibre-optic oxygen sensor in the ABO to monitor air-breathing frequency. Under normoxic conditions and in both juveniles and adults, routine air-breathing frequency was 0.03 breaths min(-1) and V(b) was about 15 mL min(-1) kg(-1). Normoxic exercise (swimming at about 1.1 body lengths s(-1)) increased air-breathing frequency by 8-fold in both groups (reaching 0.23 breaths min(-1)) and increased V(b) by 3-fold for juveniles and 2-fold for adults. Hypoxic exposure (2 kPa O2) at rest increased air-breathing frequency 19-fold (to around 0.53 breaths min(-1)) in both groups, and while V(b) again increased 3-fold in resting juvenile fish, V(b) was unchanged in resting adult fish. Exercise in hypoxia increased air-breathing frequency 35-fold (to 0.95 breaths min(-1)) in comparison with resting normoxic fish. While juvenile fish increased V(b) nearly 2-fold with exercise in hypoxia, adult fish maintained the same V(b) irrespective of exercise state and became agitated in comparison. These results imply that air-breathing during exercise and hypoxia can benefit oxygen delivery, but to differing degrees in juvenile and adult tarpon. We discuss this difference in the context of myocardial oxygen supply.