Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Among the human diseases that result from chromosomal aberrations, a de novo deletion in chromosome 11p13 is clinically associated with a syndrome characterized by Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR). Not all genes in the deleted region have been characterized biochemically or functionally. We have recently identified the first Class III cyclic nucleotide phosphodiesterase, Rv0805, from Mycobacterium tuberculosis, which biochemically and structurally belongs to the superfamily of metallophosphoesterases. We performed a large scale bioinformatic analysis to identify orthologs of the Rv0805 protein and identified many eukaryotic genes that included the human 239FB gene present in the region deleted in the WAGR syndrome. We report here the first detailed biochemical characterization of the rat 239FB protein and show that it possesses metallophosphodiesterase activity. Extensive mutational analysis identified residues that are involved in metal interaction at the binuclear metal center. Generation of a rat 239FB protein with a mutation corresponding to a single nucleotide polymorphism seen in human 239FB led to complete inactivation of the protein. A close ortholog of 239FB is found in adult tissues, and biochemical characterization of the 239AB protein demonstrated significant hydrolytic activity against 2',3'-cAMP, thus representing the first evidence for a Class III cyclic nucleotide phosphodiesterase in mammals. Highly conserved orthologs of the 239FB protein are found in Caenorhabditis elegans and Drosophila and, coupled with available evidence suggesting that 239FB is a tumor suppressor, indicate the important role this protein must play in diverse cellular events.

Tarsal tunnel syndrome: A narrative literature review

Background Tarsal tunnel syndrome is classified as a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches individually or collectively. The tunnel courses deep to fascia, the flexor retinaculum and within the abductor hallucis muscle of the foot/ankle. The condition is rare and regularly under-diagnosed leading to a range of symptoms affecting the plantar margins of the foot. There are many intervention strategies for treating tarsal tunnel syndrome with limited robust evidence to guide the clinical management of this condition. The role of conservative versus surgical interventions at various stages of the disease process remains unclear, and there is a need for a structured, step-wise approach in treating patients with this syndrome based on derived empirical evidence. This narrative review attempts to scrutinize the literature to date by clarifying initial presentation, investigations and definitive treatment for the purpose of assisting future informed clinical decision and prospective research endeavours. Process The literature searches that have been incorporated in compiling a rigorous review of this condition have included: the Cochrane Neuromuscular Group's Specialized Register (Cochrane Library 2013), the databases of EMBASE, AMED, MEDLINE, CINAHL, Physiotherapy evidence database (PEDRO), Biomed Central, Science Direct and Trip Database (1972 to the present). Reference listings of located articles were also searched and scrutinized. Authors and experts within the field of lower-limb orthopaedics were contacted to discuss applicable data. Subject-specific criteria searches utilizing the following key terms were performed across all databases: tarsal tunnel syndrome, tibial neuralgia, compression neuropathy syndromes, tibial nerve impingement, tarsal tunnel neuropathy, entrapment tibial nerve, posterior tibial neuropathy. These search strategies were modified with differing databases, adopting specific sensitivity-searching tools and functions unique to each. This search strategy identified 88 journal articles of relevance for this narrative literature review. Findings This literature review has appraised the clinical significance of tarsal tunnel syndrome, whilst assessing varied management interventions (non-surgical and surgical) for the treatment of this condition in both adults and children. According to our review, there is limited high-level robust evidence to guide and refine the clinical management of tarsal tunnel syndrome. Requirements for small-scaled randomized controlled trials in groups with homogenous aetiology are needed to analyse the effectiveness of specific treatment modalities. Conclusions It is necessary that further research endeavours be pursued for the clinical understanding, assessment and treatment of tarsal tunnel syndrome. Accordingly, a structured approach to managing patients who have been correctly diagnosed with this condition should be formulated on the basis of empirical evidence where possible.

Factors potentiating the risk of sudden infant death syndrome associated with the prone position

Background. In several studies the sudden infant death syndrome (SIDS) has been significantly associated with sleeping in the prone position. It is not known how the prone position increases the risk of SIDS. Methods. We analyzed data from a case-control study (58 infants with SIDS and 120 control infants) and a prospective cohort study (22 infants with SIDS and 213 control infants) in Tasmania. Interactions were examined in matched analyses with a multiplicative model of interaction. Results. In the case-control study, SIDS was significantly associated with sleeping in the prone position, as compared with other positions (unadjusted odds ratio, 4.5; 95 percent confidence interval, 2.1 to 9.6). The strength of this association was increased among infants who slept on natural-fiber mattresses (P = 0.05), infants who were swaddled (P = 0.09), infants who slept in heated rooms (P = 0.006), and infants who had had a recent illness (P = 0.02). These variables had no significant effect on infants who did not sleep in the prone position. A history of recent illness was significantly associated with SIDS among infants who slept prone (odds ratio, 5.7; 95 percent confidence interval, 1.8 to 19) but not among infants who slept in other positions (odds ratio, 0.83). In the cohort study, the risk of SIDS was greater among infants who slept prone on natural-fiber mattresses (odds ratio, 6.6; 95 percent confidence interval, 1.3 to 33) than among infants who slept prone on other types of mattresses (odds ratio, 1.8). Conclusions. When infants sleep prone, the elevated risk of SIDS is increased by each of four factors: the use of natural-fiber mattresses, swaddling, recent illness, and the use of heating in bedrooms.

Milk Production Responses to Oversowing a Portion of Tropical Grass Pasture with Summer Crop Legumes on Sub-tropical Dairy Farms

Northern Australian dairy farms have a large area of tropical dryland grass pasture available for use as summer pastures. Late summer-autumn in sub-tropical Australia is traditionally a difficult period in which to produce milk because of the decline in both quality and quantity of tropical grasses (Ehrlich et al. 1994). Options to improve autumn feed on dairy farms include introducing forage crops and conservation, increasing concentrate feeding and introducing legumes. Perennial tropical legumes have not been successful at this time of year because of their inability to sustain stocking rates above one cow/ha. This experiment, conducted on farms, was designed to test if annual crop legumes could be successfully oversown into tropical grass areas using minimal till methods to measure the subsequent impact on milk production on farms. Previous experiments using annual legumes in plots at Mutdapilly Research Station had demonstrated yields up to 10 t/ha can be achieved using annual tropical legumes with protein levels as high as 20% in the whole legume plant. Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.

Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis

The efficacy, adverse reactions, and long-term effects of intestinal lavage treatment with a balanced electrolyte solution (Golytely) was evaluated in patients with cystic fibrosis and distal intestinal obstruction syndrome. Twenty-two patients with cystic fibrosis (mean age 21.8 years, range 14 to 34 years, 15 boys or men) who sough medical attention because of abdominal pain and a mass in the right iliac fossa received Golytely, 5.6 ± 1.9 L (mean ± 1 SD), either orally (n = 14) or via nasogastric tube (n = 8) during 5.6 ± 2.4 hours. No serious side effects occurred. Serum electrolyte values remained within normal limits. Body weight did not change significantly. Minor adverse reactions included bloating (n = 12), nausea (n = 8), vomiting (n = 1), and chills (n = 3). All but one patient reported impressive relief of symptoms and remained pain free for an average of 3 months (range 1 to 19 months). Symptoms of abdominal pain and radiologic signs of fecal impaction assessed before and after lavage both decreased significantly (P < .0001). During follow-up (mean 15.2 months, range 4 to 26 months), 11 patients required a total of 38 (range one to nine) additional doses of Golytely. Seven patients drank the solution at home (21 treatments); only two patients chose a nasogastric tube. In ten patients with symptoms of recurrent distal intestinal obstruction syndrome prior to institution of therapy, duration of hospitalization was significantly reduced by this treatment (5.1 ± 7.6 v 2.3 ± 6.3 hospital days per annum, P < .02). It is concluded that intestinal lavage is a well-accepted, safe, and effective therapy for distal intestinal obstruction syndrome in patients with cystic fibrosis.

Behçet's syndrome involving the gastrointestinal tract: a diagnostic dilemma in childhood

Behçet's syndrome is very rare in children, especially those under 10 years of age. Clinical and radiological features are described in 4 children, including 2 under the age of 5 years, with the syndrome. As in other pediatric cases reported, the incomplete form of Behçet's syndrome was present in each case. All 4 patients had oral and genital mucosal effects, arthritis and gastrointestinal and dermatological manifestations. Ophthalmological symptoms occurred in only 1 patient. Radiologically, the 4 cases demonstrated the spectrum of gastrointestinal involvement, from minimal irregularity and thickening of the terminal ileum to gross irregularity and deformity of the terminal ileum and cecum. Because of the difficulty in differentiating Behçet's syndrome from other forms of inflammatory bowel disease it is suggested that in children with gastrointestinal involvement, 3 major criteria be present before the diagnosis of Behçet's syndrome is made.

Treatment of distal intestinal obstruction syndrome in cystic fibrosis with a balanced intestinal lavage solution

Conventional treatment of distal intestinal obstruction syndrome (DIOS) with high doses of pancreatic enzymes, mucolytic agents, and enemas is neither predictably effective nor rapid in action. In 6 cystic fibrosis patients with DIOS a balanced, non-absorbable intestinal lavage solution produced clinical and radiological improvement and striking improvement in DIOS scores. It is suggested that a balanced intestinal lavage solution should be considered as an alternative treatment for DIOS in patients with cystic fibrosis.

Feeding sorghum ergot (Claviceps africana) to sows before farrowing inhibits milk production

Objective: To assess the impact of feeding different amounts of sorghum ergot to sows before farrowing. Design: Fifty-one pregnant sows from a continually farrowing piggery were sequentially inducted into the experiment each week in groups of four to seven, as they approached within 14 days of farrowing. Diets containing sorghum ergot sclerotia within the range of 0 (control) up to 1.5% w/w (1.5% ergot provided 7 mg alkaloids/kg, including 6 mg dihydroergosine/kg) were randomly allocated and individually fed to sows. Ergot concentrations were varied with each subsequent group until an acceptable level of tolerance was achieved. Diets with ergot were replaced with control diets after farrowing. Post-farrowing milk production was assessed by direct palpation and observation of udders, and by piglet responses and growth. Blood samples were taken from sows on three days each week, for prolactin estimation. Results: Three sows fed 1.5% ergot for 6 to 10 days preceding farrowing produced no milk, and 87% of their piglets died despite supplementary feeding of natural and artificial colostrums, milk replacer, and attempts to foster them onto normally lactating sows. Ergot inclusions of 0.6% to 1.2% caused lesser problems in milk release and neo-natal piglet mortality. Of 23 sows fed either 0.3% or 0.6% ergot, lactation of only two first-litter sows were affected. Ergot caused pronounced reductions in blood prolactin, and first-litter sows had lower plasma prolactin than multiparous sows, increasing their susceptibility to ergot. Conclusion: Sorghum ergot should not exceed 0.3% (1 mg alkaloid/kg) in diets of multiparous sows fed before farrowing, and should be limited to 0.1 % for primiparous sows, or avoided completely.

Home monitoring for infants at risk of the sudden infant death syndrome

This study evaluates the effectiveness and social implications of home monitoring of 31 infants at risk of sudden infant death syndrome (SIDS). Thirteen siblings of children dying of SIDS, nine near miss SIDS infants and nine preterm infants with apnoea persisting beyond 40 weeks post conceptual age were monitored from a mean age of 15 days to a mean of 10 months. Chest movement detection monitors were used in 27 and thoracic impedance monitors in four. Genuine apnoeic episodes were reported by 21 families, and 13 infants required resuscitation. Apnoeic episodes occurred in all nine preterm infants but in only five (38%) of the siblings of SIDS (P<0.05). Troublesome false alarms were a major problem occurring with 61% of the infants and were more common with the preterm infants than the siblings of SIDS. All but two couples stated that the monitor decreased anxiety and improved their quality of life. Most parents accepted that the social restrictions imposed by the monitor were part of the caring process but four couples were highly resentful of the changes imposed on their lifestyle. The monitors used were far from ideal with malfunction occurring in 17, necessitating replacement in six, repair in six and cessation of monitoring in three. The parents became ingenious in modifying the monitors to their own individual requirements Although none of these 31 ‘at risk’ infants died the study sample was far too small to conclude whether home monitoring prevented any cases of SIDS.

Demographics, pollination syndrome and conservation status of Macrozamia platyrhachis (Zamiaceae), a geographically restricted Queensland cycad

To assess the International Union for Conservation of Nature (IUCN) status of Macrozamia platyrhachis F.M.Bailey, we surveyed this central Queensland cycad for its population abundance and health and its pollinator type and pollination syndrome (thermogenesis and volatile emissions). Plants are locally abundant within the 11 discrete populations surveyed, with an estimated population of 611 315 adult plants. Plants are highly restricted to a small area of occupancy, seed dispersal is nearly non-existent and extreme fires appear to have destroyed almost all seeds and seedlings and decimated the pollinators. Of known Macrozamia pollinators, only the thrips, Cycadothrips chadwicki Mound, were found on cones, and these were found in very low numbers. The pollination syndrome for this cycad appears to be unique, based on two cone traits. For one, thermogenesis peaks in early evening, a contrast with daytime peaks of other Cycadothrips-pollinated Macrozamia, but matches that of the Tranes weevil-pollinated Macrozamia machinii. In addition, cone volatiles include both previously unreported compounds as well as those reported exclusively on either Cycadothrips- or Tranes-pollinated species. Based on its small, fragmented area of occupancy, projected population declines and the unique pollination syndrome, we recommend that M. platyrhachis retain its current status as 'Endangered'. Habitat management plans should stipulate that controlled burns be avoided during cycad coning season and that wildfires be controlled to minimise damage to seedlings and pollinators.

Impacts of feeding system and season on milk composition and Cheddar cheese yield in a subtropical environment

Milk obtained from cows on 2 subtropical dairy feeding systems were compared for their suitability for Cheddar cheese manufacture. Cheeses were made in a small-scale cheesemaking plant capable of making 2 blocks ( about 2 kg each) of Cheddar cheese concurrently. Its repeatability was tested over 10 separate cheesemaking days with no significant differences being found between the 2 vats in cheesemaking parameters or cheese characteristics. In the feeding trial, 16 pairs of Holstein - Friesian cows were used in 2 feeding systems (M1, rain-grown tropical grass pastures and oats; and M5, a feedlot, based on maize/barley silage and lucerne hay) over 2 seasons ( spring and autumn corresponding to early and late lactation, respectively). Total dry matter, crude protein (kg/cow. day) and metabolisable energy (MJ/cow.day) intakes were 17, 2.7, and 187 for M1 and 24, 4, 260 for M5, respectively. M5 cows produced higher milk yields and milk with higher protein and casein levels than the M1 cows, but the total solids and fat levels were similar (P > 0.05) for both M1 and M5 cows. The yield and yield efficiency of cheese produced from the 2 feeding systems were also not significantly different. The results suggest that intensive tropical pasture systems can produce milk suitable for Cheddar cheese manufacture when cows are supplemented with a high energy concentrate. Season and stage of lactation had a much greater effect than feeding system on milk and cheesemaking characteristics with autumn ( late lactation) milk having higher protein and fat contents and producing higher cheese yields.

Cortical processing of speech and non-speech sounds in autism and Asperger syndrome

Autism and Asperger syndrome (AS) are neurodevelopmental disorders characterised by deficient social and communication skills, as well as restricted, repetitive patterns of behaviour. The language development in individuals with autism is significantly delayed and deficient, whereas in individuals with AS, the structural aspects of language develop quite normally. Both groups, however, have semantic-pragmatic language deficits. The present thesis investigated auditory processing in individuals with autism and AS. In particular, the discrimination of and orienting to speech and non-speech sounds was studied, as well as the abstraction of invariant sound features from speech-sound input. Altogether five studies were conducted with auditory event-related brain potentials (ERP); two studies also included a behavioural sound-identification task. In three studies, the subjects were children with autism, in one study children with AS, and in one study adults with AS. In children with autism, even the early stages of sound encoding were deficient. In addition, these children had altered sound-discrimination processes characterised by enhanced spectral but deficient temporal discrimination. The enhanced pitch discrimination may partly explain the auditory hypersensitivity common in autism, and it may compromise the filtering of relevant auditory information from irrelevant information. Indeed, it was found that when sound discrimination required abstracting invariant features from varying input, children with autism maintained their superiority in pitch processing, but lost it in vowel processing. Finally, involuntary orienting to sound changes was deficient in children with autism in particular with respect to speech sounds. This finding is in agreement with previous studies on autism suggesting deficits in orienting to socially relevant stimuli. In contrast to children with autism, the early stages of sound encoding were fairly unimpaired in children with AS. However, sound discrimination and orienting were rather similarly altered in these children as in those with autism, suggesting correspondences in the auditory phenotype in these two disorders which belong to the same continuum. Unlike children with AS, adults with AS showed enhanced processing of duration changes, suggesting developmental changes in auditory processing in this disorder.

The influence of temperature on the foaming of milk

The effect of temperature (5-85 °C) on the foaming properties of cows' milk was investigated. The foaming properties of milk as a function of temperature varied considerably depending on fat content and the processing conditions used in manufacture. Skim milk foams were most stable when formed at 45 °C. Milk fat had a detrimental effect on foam formation and stability of whole milk especially in the temperature range 15-45 °C. The detrimental effects of milk fat on foaming properties were reduced by homogenization and ultra-high-temperature (UHT) treatment. No correlation was observed between foam formation and surface tension of whole milk in the temperature range 15-45 °C. There was a pronounced difference in the bubble size distributions of whole milk and skim milk especially at half-life of the foams. Bubbles in whole milk foams were smaller and showed a higher degree of rupture as a result of coalescence than those in skim milk foams.

The effects of high stocking rates on milk production from dryland and irrigated Mediterranean pastures

An experiment using herds of similar to 20 cows (farmlets) assessed the effects of high stocking rates on production and profitability of feeding systems based on dryland and irrigated perennial ryegrass-based pastures in a Mediterranean environment in South Australia over 4 years. A target level of milk production of 7000 L/cow.year was set, based on predicted intakes of 2.7 t DM/cow.year as concentrates, pasture intakes from 1.5 to 2.7 t/cow.year and purchased fodder. In years 1 and 2, up to 1.5 t DM/cow.year of purchased fodder was used and in years 3 and 4 the amounts were increased if necessary to enable levels of milk production per cow to be maintained at target levels. Cows in dryland farmlets calved in March to May inclusive and were stocked at 2.5, 2.9, 3.3, 3.6 and 4.1 cows/ha, while those in irrigated farmlets calved in August to October inclusive and were stocked at 4.1, 5.2, 6.3 and 7.4 cows/ha. In the first 2 years, when inputs of purchased fodder were limited, milk production per cow was reduced with higher stocking rates (P < 0.01), but in years 3 and 4 there were no differences. Mean production was 7149 kg/cow.year in years 1 and 2, and 8162 kg/cow.year in years 3 and 4. Production per hectare was very closely related to stocking rate in all years (P < 0.01), increasing from 18 to 34 t milk/ha.year for dryland farmlets (1300 to 2200 kg milk solids/ha) and from 30 to 60 t milk/ha.year for irrigated farmlets (2200 to 4100 kg milk solids/ha). Almost all of these increases were attributed to the increases in grain and purchased fodder inputs associated with the increases in stocking rate. Net pasture accumulation rates and pasture harvest were generally not altered with stocking rate, though as stocking rate increased there was a change to more of the pasture being grazed and less conserved in both dryland and irrigated farmlets. Total pasture harvest averaged similar to 8 and 14 t DM/ha.year for dryland and irrigated pastures, respectively. An exception was at the highest stocking rate under irrigation, where pugging during winter was associated with a 14% reduction in annual pasture growth. There were several indications that these high stocking rates may not be sustainable without substantial changes in management practice. There were large and positive nutrient balances and associated increases in soil mineral content (P < 0.01), especially for phosphorus and nitrate nitrogen, with both stocking rate and succeeding years. Levels under irrigation were considerably higher (up to 90 and 240 mg/kg of soil for nitrate nitrogen and phosphorus, respectively) than under dryland pastures (60 and 140 mg/kg, respectively). Soil organic carbon levels did not change with stocking rate, indicating a high level of utilisation of forage grown. Weed ingress was also high (to 22% DM) in all treatments and especially in heavily stocked irrigated pastures during winter. It was concluded the higher stocking rates used exceeded those that are feasible for Mediterranean pastures in this environment and upper levels of stocking are suggested to be 2.5 cows/ha for dryland pastures and 5.2 cows/ha for irrigated pastures. To sustain these suggested stocking rates will require further development of management practices to avoid large increases in soil minerals and weed invasion of pastures.