Drivers of ecological assembly in the hindgut of Atlantic Cod fed a macroalgal supplemented diet.

It is difficult to disentangle the many variables (e.g. internal or external cues and random events) that shape the microbiota in the gastrointestinal tract of any living species. Ecological assembly processes applied to microbial communities can elucidate these drivers. In our study, farmed Atlantic cod (Gadus morhua) were fed a diet of 10% macroalgae supplement (Ulva rigida [ULVA] or Ascophyllum nodosum [ASCO] or a non-supplemented control diet [CTRL]) over 12 weeks. We determined the influence of ecological assembly processes using a suite of null-modelling tools. We observed dissimilarity in the abundance of common OTUs over time, which was driven by deterministic assembly. The CTRL samples showed selection as a critical assembly process. While dispersal limitation was a driver of the gut microbiome for fish fed the macroalgae supplemented diet at Week 12 (i.e., ASCO and ULVA). Fish from the ASCO grouping diverged into ASCO_N (normal) and ASCO_LG (lower growth), where ASCO_LG individuals found the diet unpalatable. The recruitment of new taxa overtime was altered in the ASCO_LG fish, with the gut microbiome showing phylogenetic underdispersion (nepotistic species recruitment). Finally, the gut microbiome (CTRL and ULVA) showed increasing robustness to taxonomic disturbance over time and lower functional redundancy. This study advances our understanding of the ecological assembly and succession in the hindgut of juvenile Atlantic cod across dietary treatments. Understanding the processes driving ecological assembly in the gut microbiome, in fish research specifically, could allow us to manipulate the microbiome for improved health or resilience to disease for improved aquaculture welfare and production.

Measuring interoception: The phase adjustment task.

Interoception, perception of one's bodily state, has been associated with mental health and socio-emotional processes. However, several interoception tasks are of questionable validity, meaning associations between interoception and other variables require confirmation with new measures. Here we describe the novel, smartphone-based Phase Adjustment Task (PAT). Tones are presented at the participant's heart rate, but out of phase with heartbeats. Participants adjust the phase relationship between tones and heartbeats until they are synchronous. Data from 124 participants indicates variance in performance across participants which is not affected by physiological or strategic confounds. Associations between interoception and anxiety, depression and stress were not significant. Weak associations between interoception and mental health variables may be a consequence of testing a non-clinical sample. A second study revealed PAT performance to be moderately stable over one week, consistent with state effects on interoception.

Temporal changes in the gut microbiota in farmed Atlantic cod (Gadus morhua) outweigh the response to diet supplementation with macroalgae.

BACKGROUND: Aquaculture successfully meets global food demands for many fish species. However, aquaculture production of Atlantic cod (Gadus morhua) is just 2.5% of total market production. For cod farming to be a viable economic venture specific challenges on how to increase growth, health and farming productivity need to be addressed. Feed ingredients play a key role here. Macroalgae (seaweeds) have been suggested as a functional feed supplement with both health and economic benefits for terrestrial farmed animals and fish. The impact of such dietary supplements to cod gut integrity and microbiota, which contribute to overall fish robustness is unknown. The objective of this study was to supplement the diet of juvenile Atlantic cod with macroalgae and determine the impacts on fish condition and growth, gut morphology and hindgut microbiota composition (16S rRNA amplicon sequencing). Fish were fed one of three diets: control (no macroalgal inclusion), 10% inclusion of either egg wrack (Ascophyllum nodosum) or sea lettuce (Ulva rigida) macroalgae in a 12-week trial. RESULTS: The results demonstrated there was no significant difference in fish condition, gut morphology or hindgut microbiota between the U. rigida supplemented fish group and the control group at any time-point. This trend was not observed with the A. nodosum treatment. Fish within this group were further categorised as either 'Normal' or 'Lower Growth'. 'Lower Growth' individuals found the diet unpalatable resulting in reduced weight and condition factor combined with an altered gut morphology and microbiome relative to the other treatments. Excluding this group, our results show that the hindgut microbiota was largely driven by temporal pressures with the microbial communities becoming more similar over time irrespective of dietary treatment. The core microbiome at the final time-point consisted of the orders Vibrionales (Vibrio and Photobacterium), Bacteroidales (Bacteroidetes and Macellibacteroides) and Clostridiales (Lachnoclostridium). CONCLUSIONS: Our study indicates that U. rigida macroalgae can be supplemented at 10% inclusion levels in the diet of juvenile farmed Atlantic cod without any impact on fish condition or hindgut microbial community structure. We also conclude that 10% dietary inclusion of A. nodosum is not a suitable feed supplement in a farmed cod diet.

"It's the single best thing I've done in the last 10 years": a qualitative study exploring patient and dietitian experiences with, and perceptions of, a multi-component dietary weight loss program for knee osteoarthritis.

OBJECTIVE: Explore patient and dietitian experiences with a multi-component dietary weight loss program for knee osteoarthritis to understand enablers and challenges to success at 6-months. DESIGN: Qualitative study embedded within a randomised controlled trial. Semi-structured individual interviews with 24 patients with knee osteoarthritis who undertook, and five dietitians who supervised, a weight management program (involving a ketogenic very low calorie diet (VLCD), video consultations, educational resources) over 6 months. Data were thematically analysed. RESULTS: Five themes were developed: (1) ease and convenience of program facilitated adherence (structure and simplicity of the meal replacements; not feeling hungry on diet; convenience of consulting via video) (2) social and professional support crucial for success (encouragement from partner, family, and friends; guidance from, and accountability to, dietitian; anxiety around going at it alone) (3) program was engaging and motivating (determination to stick to program; rapid weight loss helped motivation) (4) holistic nature of program was important (suite of high-quality educational resources; exercise important to compliment weight loss) (5) rewarding experience and lifelong impact (improved knee pain and function; positive lifestyle change). CONCLUSIONS: Patients and dietitians described positive experiences with the weight management program, valuing its simplicity, effectiveness, and convenience. Support from dietitians and a comprehensive suite of educational resources, incorporated with an exercise program, were considered crucial for success. Findings suggest this multi-component dietary program is an acceptable weight loss method in people with knee osteoarthritis that may benefit symptoms. Strategies for supporting long-term independent weight management should be a focus of future research.

Cold adaptation and replicable microbial community development during long-term low-temperature anaerobic digestion treatment of synthetic sewage.

The development and activity of a cold-adapting microbial community was monitored during low-temperature anaerobic digestion (LtAD) treatment of wastewater. Two replicate hybrid anaerobic sludge bed-fixed-film reactors treated a synthetic sewage wastewater at 12°C, at organic loading rates of 0.25-1.0 kg chemical oxygen demand (COD) m-3 d-1, over 889 days. The inoculum was obtained from a full-scale anaerobic digestion reactor, which was operated at 37°C. Both LtAD reactors readily degraded the influent with COD removal efficiencies regularly exceeding 78% for both the total and soluble COD fractions. The biomass from both reactors was sampled temporally and tested for activity against hydrolytic and methanogenic substrates at 12°C and 37°C. Data indicated that significantly enhanced low-temperature hydrolytic and methanogenic activity developed in both systems. For example, the hydrolysis rate constant (k) at 12°C had increased 20-30-fold by comparison to the inoculum by day 500. Substrate affinity also increased for hydrolytic substrates at low temperature. Next generation sequencing demonstrated that a shift in a community structure occurred over the trial, involving a 1-log-fold change in 25 SEQS (OTU-free approach) from the inoculum. Microbial community structure changes and process performance were replicable in the LtAD reactors.

Impact of macromolecular crowding on RNA/spermine complex coacervation and oligonucleotide compartmentalization.

We report the effect of neutral macromolecular crowders poly(ethylene glycol) (PEG) (8 kDa) and Ficoll (70 kDa) on liquid-liquid phase separation in a polyuridylic acid (polyU)/spermine complex coacervate system. The addition of PEG decreased both the amount of spermine required for phase separation and the coacervation temperature (TC). We interpret these effects on phase behavior as arising due to excluded volume and preferential interactions on both the secondary structure/condensation of spermine-associated polyU molecules and on the association of soluble polyU/spermine polyelectrolyte complexes to form coacervate droplets. Examination of coacervates formed in the presence of fluorescently-labeled PEG or Ficoll crowders indicated that Ficoll is accumulated while PEG is excluded from the coacervate phase, which provides further insight into the differences in phase behavior. Crowding agents impact distribution of a biomolecular solute: partitioning of a fluorescently-labeled U15 RNA oligomer into the polyU/spermine coacervates was increased approximately two-fold by 20 wt% Ficoll 70 kDa and by more than two orders of magnitude by 20 wt% PEG 8 kDa. The volume of the coacervate phase decreased in the presence of crowder relative to a dilute buffer solution. These findings indicate that potential impacts of macromolecular crowding on phase behavior and solute partitioning should be considered in model systems for intracellular membraneless organelles.

Trends in child and adolescent obesity prevalence in economically advanced countries according to socioeconomic position: a systematic review.

Recent obesity trends in children and adolescents suggest a plateau. However, it is unclear whether such trends have been experienced across socioeconomic groups. We analysed whether recent trends in child and adolescent overweight and obesity differ by socioeconomic position (SEP) across economically advanced countries. Eligible studies reported overweight and obesity prevalence in children and/or adolescents (2-18 years), for at least two time points since 1990, stratified by SEP. Socioeconomic differences in trends in child and adolescent overweight and obesity over time were analysed. Differences in trends between SEP groups were observed across a majority of studies. Over half the studies indicated increasing prevalence among low SEP children and adolescents compared to a third of studies among children and adolescents with a high SEP. Around half the studies indicated widening socioeconomic inequalities in overweight and obesity. Since 2000 a majority of studies demonstrated no change or a decrease in prevalence among both high and low SEP groups. However around 40% of studies indicated widening of socioeconomic inequalities post-2000. While our study provides grounds for optimism, socioeconomic inequalities in overweight and obesity continue to widen. These findings highlight the need for greater consideration of different population groups when implementing obesity interventions.

Mechanisms contributing to visceral hypersensitivity: focus on splanchnic afferent nerve signaling.

BACKGROUND: Visceral hypersensitivity is a main characteristic of functional bowel disorders and is mediated by both peripheral and central factors. We investigated whether enhanced splanchnic afferent signaling in vitro is associated with visceral hypersensitivity in vivo in an acute and postinflammatory rat model of colitis. METHODS: Trinitrobenzene sulfonic acid (TNBS)-colitis was monitored individually by colonoscopy to confirm colitis and follow convalescence and endoscopic healing in each rat. Experiments were performed in controls, rats with acute colitis and in postcolitis rats. Colonic afferent mechanosensitivity was assessed in vivo by quantifying visceromotor responses (VMRs), and by making extracellular afferent recordings from splanchnic nerve bundles in vitro. Multiunit afferent activity was classified into single units identified as low threshold (LT), wide dynamic range (WDR), high threshold (HT), and mechanically insensitive afferents (MIA). KEY RESULTS: During acute TNBS-colitis, VMRs were significantly increased and splanchnic nerve recordings showed proportionally less MIA and increased WDR and HT afferents. Acute colitis gave rise to an enhanced spontaneous activity of both LT and MIA and augmented afferent mechanosensitivity in LT, WDR and HT afferents. Postcolitis, VMRs remained significantly increased, whereas splanchnic nerve recordings showed that the proportion of LT, WDR, HT and MIA had normalized to control values. However, LT and MIA continued to show increased spontaneous activity and WDR and HT remained sensitized to colorectal distension. CONCLUSIONS & INFERENCES: Visceral hypersensitivity in vivo is associated with sensitized splanchnic afferent responses both during acute colitis and in the postinflammatory phase. However, splanchnic afferent subpopulations are affected differentially at both time points.

Trends in body mass index according to educational attainment for urban Australian adults between 1980 and 2007.

BACKGROUND: We have previously demonstrated that between the years 1980 and 2000, the mean body mass index (BMI) of the urban Australian population increased, with greater increases observed with increasing BMI. The current study aimed to quantify trends over time in BMI according to level of education between 1980 and 2007. METHODS: We compared data from the 1980, 1983 and 1989 National Heart Foundation Risk Factor Prevalence Studies, 1995 National Nutrition Survey, 2000 Australian Diabetes, Obesity and Lifestyle Study and the 2007 National Health Survey. For survey comparability, analyses were restricted to urban Australian residents aged 25-64 years. BMI was calculated from measured height and weight. The education variable was dichotomised at completion of secondary school. Four age-standardised BMI indicators were compared over time by sex and education: mean BMI, mean BMI of the top 5% of the BMI distribution, prevalence of obesity (BMI⩾30 kg m(-)(2)), prevalence of class II(+) obesity (BMI⩾35 kg m(-)(2)). RESULTS: Between 1980 and 2007, the mean BMI among men increased by 2.5 and 1.7 kg m(-)(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 20 (from 12-32%) and 11 (10-21%) %-points. Among women, mean BMI increased by 2.9 and 2.4 kg m(-)(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 16 (12-28%) and 12 (7-19%) %-points. The prevalence of class II(+) obesity among men increased by 9 (1-10%) and 4 (1-5%) %-points for those with low and high education levels, and among women increased by 8 (4-12%) and 4 (2-6%) %-points. Absolute and relative differences between education groups generally increased over time. CONCLUSIONS: Educational differences in BMI have persisted among urban Australian adults since 1980 without improvement. Obesity prevention policies will need to be effective in those with greatest socio-economic disadvantage if we are to equitably and effectively address the population burden of obesity and its corollaries.

Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies.

Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery.

Translational potential of a mouse in vitro bioassay in predicting gastrointestinal adverse drug reactions in Phase I clinical trials.

BACKGROUND: Motility-related gastrointestinal (GI) adverse drug reactions (GADRs) such as diarrhea and constipation are a common and deleterious feature associated with drug development. Novel biomarkers of GI function are therefore required to aid decision making on the GI liability of compounds in development. METHODS: Fifteen compounds associated with or without clinical GADRs were used to assess the ability of an in vitro colonic motility bioassay to predict motility-related GADRs. Compounds were examined in a blinded fashion for their effects on mouse colonic peristaltic motor complexes in vitro. For each compound concentration-response relationships were determined and the results compared to clinical data. Compounds were also assessed using GI transit measurements obtained using an in vivo rat charcoal meal model. KEY RESULTS: Within a clinically relevant dosing range, the in vitro assay identified five true and three false positives, four true and three false negatives, which gave a predictive capacity of 60%. The in vivo assay detected four true and four false positives, four false and three true negatives, giving rise to a predictive capacity for this model of 47%. CONCLUSIONS & INFERENCES: Overall these results imply that both assays are poor predictors of GADRs. Further analysis would benefit from a larger compound set, but the data show a clear need for improved models for use in safety pharmacology assessment of GI motility.

Outcomes in young adulthood: are we achieving community participation and inclusion?

BACKGROUND: Despite recognition of the importance of integrated community living and support, there is evidence that parents remain the primary caregivers of young adults with intellectual disability (ID). In addition, employment rates remain low in this population. This study aimed to investigate the changes in living arrangements and participation in daytime activities over time in a community population of young people with ID. METHOD: The sample consisted of 536 participants aged 4.0-18.9 years at Wave 1, followed up at Wave 5 when aged 20.5-37.6 years. Information was collected on their living arrangements and daytime activities at both time points, along with living skills and information on community social inclusion at Wave 5. For parents still caring for their adult child with ID, information was also collected on parental ratings of their own mental and physical health, and their satisfaction with the long-term care arrangements for their adult child. RESULTS: A significant proportion of young people were still living with their parents at Wave 5. A greater proportion of those with a severe-profound degree of ID were living in residential care. Parents caring for their adult child reported high levels of mental health problems and dissatisfaction with the long-term care arrangements for their child. A small proportion of young people were in paid employment, and the majority was engaged in structured activities provided for those with an ID. Over one-third of the sample participated in a structured daytime activity for 10 or fewer hours per week, and 7% were not engaged in any structured daytime activity. CONCLUSIONS: These results suggest that adequate provision of accommodation and employment services for young adults with an ID is lacking. In many cases the responsibility of care continues to reside with parents as their children transition from childhood to adulthood. Greater attention is needed to address these issues and facilitate social inclusion and integration for young people with ID.

Pharmaceutical utilisation and costs before and after bariatric surgery.

OBJECTIVE: To determine whether pharmaceutical utilisation and costs change after bariatric surgery. SUBJECTS: Total population of Australians receiving Medicare-subsidised laparoscopic adjustable gastric banding (LAGB) in 2007 (n=9542). DESIGN: Computerised data linkage with Medicare, Australia's universal tax-funded health insurance scheme. Pharmaceuticals relating to obesity-related disease and postsurgical management were assigned to therapeutic categories and analysed. The mean annual numbers of pharmaceutical prescriptions for each category were compared over the 4-year period from the year before LAGB (2006) to 2 years after LAGB (2009) using utilisation incidence rate ratios (IRRs). RESULTS: The population was mainly female (77.7%) and age was normally distributed with the majority (60.7%) of subjects aged between 35-54 years. Utilisation rates decreased significantly after LAGB in the following therapeutic categories: diabetes (IRR 0.51, IRR 95% CI 0.50-0.53, mean annual cost differences per person $30), cardiovascular (0.81, 0.80-0.82, $29), psychiatric (0.95, 0.93-0.97, $13), rheumatic and inflammatory disorders (0.51, 0.49-0.53, $10) and asthma (0.78, 0.75-0.81, $9). In contrast, significantly greater utilisation was observed in the pain (1.28, 1.23-1.32, $12), gastrointestinal tract disorder (1.04, 1.02-1.07, $5) and anaemia/vitamins (2.34, 2.01-2.73, $4) therapeutic categories. When the defined categories were combined, a net reduction in pharmaceutical utilisation was observed, from 10.5 to 9.6 pharmaceuticals prescribed per person/year, and costs decreased from $AUD517 to $AUD435 per year in 2009 prices. CONCLUSION: Relative to the year before LAGB, overall pharmaceutical utilisation was reduced in the 2 years after the year of LAGB surgery, demonstrating that bariatric surgery can lead to reductions in pharmaceutical utilisation in the 'real world' setting. The greatest absolute cost reductions were observed in the therapies to treat diabetes and cardiovascular disease.

The hydrolysis and biogas production of complex cellulosic substrates using three anaerobic biomass sources.

In this study, the ability of various sludges to digest a diverse range of cellulose and cellulose-derived substrates was assessed at different temperatures to elucidate the factors affecting hydrolysis. For this purpose, the biogas production was monitored and the specific biogas activity (SBA) of the sludges was employed to compare the performance of three anaerobic sludges on the degradation of a variety of complex cellulose sources, across a range of temperatures. The sludge with the highest performance on complex substrates was derived from a full-scale bioreactor treating sewage at 37 °C. Hydrolysis was the rate-limiting step during the degradation of complex substrates. No activity was recorded for the synthetic cellulose compound carboxymethylcellulose (CMC) using any of the sludges tested. Increased temperature led to an increase in hydrolysis rates and thus SBA values. The non-granular nature of the mesophilic sludge played a positive role in the hydrolysis of solid substrates, while the granular sludges proved more effective on the degradation of soluble compounds.

Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves.

Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 1-2-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (70-85% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra-axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well-specified sequences of solutions containing FDA-approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca²âº-free saline containing antioxidants (especially methylene blue) that inhibit plasmalemmal sealing in sciatic nerves in vivo, ex vivo, and in rat B104 hippocampal cells in vitro. Second, a hypotonic solution of polyethylene glycol (PEG) is applied to open closely apposed (by microsutures, if cut) axonal ends to induce their membranes to flow rapidly into each other (PEG-fusion), consistent with data showing that PEG rapidly seals (PEG-seals) transected neurites of B104 cells, independently of any known endogenous sealing mechanism. Third, Ca²âº-containing isotonic saline is applied to induce sealing of any remaining plasmalemmal holes by Ca²âº-induced accumulation and fusion of vesicles. These and other data suggest that PEG-sealing is neuroprotective, and our PEG-fusion protocols that repair cut- and crush-severed rat nerves might rapidly translate to clinical procedures.

Preliminary analysis of the cost-effectiveness of the National Bowel Cancer Screening Program: demonstrating the potential value of comprehensive real world data.

BACKGROUND/AIM: The complexity and cost of treating cancer patients is escalating rapidly and increasingly difficult decisions are being made regarding which interventions provide value for money. BioGrid Australia supports collection and analysis of comprehensive treatment and outcome data across multiple sites. Here, we use preliminary data regarding the National Bowel Cancer Screening Program (NBCSP) and stage-specific treatment costs for colorectal cancer (CRC) to demonstrate the potential value of real world data for cost-effectiveness analyses (CEA). METHODS: Data regarding the impact of NBCSP on stage at diagnosis were combined with stage-specific CRC treatment costs and existing literature. An incremental CEA was undertaken from a government healthcare perspective, comparing NBCSP with no screening. The 2008 invited population (n= 681,915) was modelled in both scenarios. Effectiveness was expressed as CRC-related life years saved (LYS). Costs and benefits were discounted at 3% per annum. RESULTS: Over the lifetime and relative to no screening, NBCSP was predicted to save 1265 life years, prevent 225 CRC cases and cost an additional $48.3 million, equivalent to a cost-effectiveness ratio of $38,217 per LYS. A scenario analysis assuming full participation improved this to $23,395. CONCLUSIONS: This preliminary CEA based largely on contemporary real world data suggests population-based faecal occult blood test screening for CRC is attractive. Planned ongoing data collection will enable repeated analyses over time, using the same methodology in the same patient populations, permitting an accurate analysis of the impact of new therapies and changing practice. Similar CEA using real world data related to other disease types and interventions appears desirable.

Inter-rater reliability of the Developmental Behaviour Checklist for Adults in community accommodation settings.

BACKGROUND: With the publication of the Developmental Behaviour Checklist for Adults (DBC-A), people of all ages with intellectual disability (ID) can now be assessed using a carer-completed screening checklist of emotional and behavioural disturbance. This provides a broad assessment framework across the life span, assists the process of clinical assessment, diagnosis and management, and, through efficient screening, helps ensure that people with ID and high levels of disturbed behaviour are more likely to receive the often scarce and costly behavioural and mental health services that are available. Earlier studies have reported acceptable results of test-retest reliability studies with family members and paid carers in community settings and the results of an inter-rater reliability study completed with family members. This study reports on another aspect of DBC-A reliability, inter-rater reliability with paid carers, in two small community-based accommodation settings. METHOD: Participants were 38 pairs of paid carers employed by two non-government agencies providing residential services in small group homes to 38 adults with ID in the community. RESULTS: An intraclass correlation coefficient (ICC) of 0.69 (n = 38, 95% CI 0.54-0.86) was found between pairs of paid carers employed in small group homes. DISCUSSION: Pairs of paid carers working with adults with ID in small group homes reliably completed DBC-A checklists. An ICC result of 0.69 compares favourably with the results of an earlier inter-rater study completed with the family members of people with ID living in the community. Inter-rater reliability on the six DBC-A sub-scales was also computed and the results were satisfactory. CONCLUSIONS: The carer-completed DBC-A provides a broad and comprehensive survey of the emotional and behavioural problems of adults with ID. It has satisfactory psychometric properties, which have been further extended. The DBC-A can be used in clinical, research and service settings to assess psychopathology across the adult life span in people with ID.

The flow patterns of caudal epidural in upper lumbar spinal pathology.

Epidural steroid injections are an important therapeutic modality employed by spinal surgeons in the treatment of patients with chronic low back pain with or without lumbar radiculopathy. The caudal epidural is a commonly used and well-established technique; however, little is known about the segmental level of pathology that may be addressed by this intervention. This prospective study of over 50 patients aimed to examine the spreading pattern of this technique using epidurography. The effect of variation in Trendelenburg tilt and the eradication of lumbar lordosis on the cephalic distribution of the injectate were investigated. 52 patients with low back pain and radiculopathy underwent caudal epidural. All had 20 ml volume injected, comprised of 5 ml contrast (Ultravist™ Schering) 2 ml Triamcinolone (Adcortyl™ Squibb) and 13 ml local anaesthetic (1% lignocaine). Patients were randomised to either 0° or 30° of Trendelenburg tilt, as referenced from the lumbar spine. Patients were further randomised to presence or absence of lumbar lordosis, which was eradicated using a flexion device placed beneath the prone patient. A lateral image of each sacrum was obtained, to identify variations in sacral geometry particularly resistant to cephalic spread of injectate. The highest segment reached on fluoroscopy was recorded post injection. Fifty-two patients with a mean age of 50 years underwent caudal epidural. Thirty-one were in 0° head tilt, with 21 in 30° of head tilt. In each of these groups, 50% had their lumbar lordosis flattened prior to caudal injection. The median segmental level reached was L3, with a range from T9 to L5. Eradication of lumbar lordosis did not significantly alter cephalic spread of injectate. There was a trend for 30° tilt to extend the upper level reached by caudal injection (p=0.08). There were no adverse events in this series. Caudal epidural is a reliable and relatively safe procedure for the treatment of low back pain. Pathology at L3/4 and L4/5 and L5/S1 can be approached by this technique. Although in selected cases thoracic and high lumbar levels can be reached, this is variable. If pathology at levels above L3 needs to be addressed, we propose a 30° head tilt may improve cephalic drug delivery. The caudal route is best reserved for pathology below L3.

Purinergic contribution to small intestinal afferent hypersensitivity in a murine model of postinfectious bowel disease.

Increased sensitivity of the afferent innervation of the gastrointestinal tract reportedly underlies symptoms of discomfort and pain in functional bowel disorders. The present investigation aimed to examine whether the purinergic P2X(2) and P2X(3) receptor subunits contribute to the mechanosensitivity of small intestinal afferents in normal mice and in a murine model of postinfectious gut dysfunction. Mesenteric afferent nerve activity was recorded in a mouse jejunum preparation maintained in vitro. As has been shown previously, ramp distension of the jejunal segment evoked biphasic afferent discharge, reflecting activation of low and high threshold fibres. The average pressure-afferent response curve in mice deficient in both P2X(2) and P2X(3) subunits (n = 14) was not significantly different from that of the wild-type control preparations (n = 13). Application of pyridoxal 5-phosphate 6-azophenyl-2 ,4-disulphonic acid (PPADS) (30 micromol L(-1)), a P2X and P2Y antagonist, or 2,4,6-trinitrophenol-adenosine 5'-triphosphate (10 micromol L(-1)), an antagonist selective for homomeric P2X(3) and heteromeric P2X(2/3) receptors, had no effect on the averaged pressure-afferent response curve in wild-type animals. In Trichinella spiralis-infected mice, the magnitude of mesenteric afferent responses to jejunal distension was greater at day 21 and day 56 postinfection compared with the sham control preparations demonstrating the development of afferent hypersensitivity. PPADS had no significant effect upon mechanically evoked afferent discharge rates in sham treated preparations (n = 5), but significantly inhibited afferent sensitivity to jejunal distension in preparations from mice at day 21 (n = 6) and day 56 (n = 7) postinfection. These results suggest that purinergic mechanisms play no role in mechanosensory transduction in the normal small intestine but contribute significantly to postinfectious mechano-hypersensitivity.