Modelling learning in Caenorhabditis elegans chemosensory and locomotive circuitry for T-maze navigation.

Recently, a new type of Caenorhabditis elegans associative learning was reported, where nematodes learn to reach a target arm in an empty T-maze, after they have successfully located reward (food) in the same side arm of a similar, baited, training maze. Here, we present a simplified mathematical model of C. elegans chemosensory and locomotive circuitry that replicates C. elegans navigation in a T-maze and predicts the underlying mechanisms generating maze learning. Based on known neural circuitry, the model circuit responds to food-released chemical cues by modulating motor neuron activity that drives simulated locomotion. We show that, through modulation of interneuron activity, such a circuit can mediate maze learning by acquiring a turning bias, even after a single training session. Simulated nematode maze navigation during training conditions in food-baited mazes and during testing conditions in empty mazes is validated by comparing simulated behaviour with new experimental video data, extracted through the implementation of a custom-made maze tracking algorithm. Our work provides a mathematical framework for investigating the neural mechanisms underlying this novel learning behaviour in C. elegans. Model results predict neuronal components involved in maze and spatial learning and identify target neurons and potential neural mechanisms for future experimental investigations into this learning behaviour.

Norovirus in the hospital setting: virus introduction and spread within the hospital environment.

Norovirus (NoV) strains were collected over a four-month period during 2009-2010 from hospitalised patients with symptoms of gastroenteritis. These were characterised in order to estimate how many strains were introduced into the hospital from the community. In addition, environmental swabbing was performed after clinical cleaning of bays or wards accommodating infected patients. This was performed in order to assess the efficiency of cleaning and identify any NoV contamination in the environment. A total of eight distinct genetic clusters of NoV GII-4 genotype were identified during the four-month period, with some wards experiencing multiple outbreaks with different GII-4 strains during the season. NoV was detected from 31.4% of environmental swabs post cleaning. Notes trolleys, computer keyboards, soap and alcohol dispensers, blood pressure equipment, pulse oximeters and tympanic thermometers were identified as NoV reservoirs but contamination was also found on surfaces around the bedside environment, and furniture, fixtures and fittings associated with toilets and shower rooms. The combination of detailed virus characterisation and environmental swabbing is a powerful tool for infection control audits to determine the size and scope of an outbreak and to monitor the efficiency of clinical cleaning.

Early versus delayed treatment of extension type-3 supracondylar fractures of the humerus in children.

We examined differences in the rate of open reduction, operating time, length of hospital stay and outcome between two groups of children with displaced supracondylar fractures of the humerus who underwent surgery either within 12 hours of the injury or later. There were 77 children with type-3 supracondylar fractures. Of these, in 43 the fracture was reduced and pinned within 12 hours and in 34 more than 12 hours after injury. Both groups were similar in regard to gender, age and length of follow-up. Bivariate and logistical regression analysis showed no statistical difference between the groups. The number of peri-operative complications was low and did not affect the outcome regardless of the timing of treatment. Our study confirmed that the treatment of uncomplicated displaced supracondylar fractures of the humerus can be early or delayed. In these circumstances operations at night can be avoided.

The development of an innovative education curriculum for 11-16 yr old children with type 1 diabetes mellitus (T1DM).

BACKGROUND: Evidence-based, structured education is recommended for all people with diabetes; tailored to meet their personal needs and learning styles. Adult courses exist in the UK but are of limited value for children. The aim of this study was to adapt the adult Dose Adjustment For Normal Eating (DAFNE) course to design a skills training course, for children aged 11-16 yr, focusing on self-management skills within an intensive insulin regime. To ensure that the course format meets the developmental, intellectual and social needs of children and adolescents and is delivered using educationally sound techniques. METHODS: Relevant professionals and potential users of the course were involved in curriculum design and content in the following ways: (i) The views of 95 pediatric diabetes specialist nurses were sought through a postal survey; (ii) Focus group discussions were conducted with children with type 1 diabetes mellitus (T1DM) and their families to contribute to content and design; and (iii) Secondary school teachers worked with experienced pediatric diabetes staff advising on educational content and teaching format. RESULTS: The developed curriculum uses a progressive modular-based structure to improve self-management in a variety of medical and social situations. It has clear learning objectives and is based on the format of UK schools curricula. Additional support is provided through dedicated parent sessions, involvement of friends and the provision of a school resource pack. CONCLUSION: Collaborative working between health professionals, school teachers and families has resulted in an age-appropriate curriculum, which employs validated educational techniques. This will be refined following pilot courses before formal evaluation in a multicentre randomized controlled trial.

Osteotomy for congenital elevation of the scapula (Sprengel's deformity).

We report 12 consecutive cases of vertical scapular osteotomy to correct Sprengel's deformity, performed during a 16-year period, with a mean follow-up of 10.4 years. The mean increase in abduction of the shoulder was 53 degrees . The cosmetic appearance improved by a mean of 1.5 levels on the Cavendish scale. Neither function nor cosmesis deteriorated with time. We recommend the procedure for correction of moderate deformities with a functional deficit.

PAK4 kinase is essential for embryonic viability and for proper neuronal development.

The serine/threonine kinase PAK4 is a target for the Rho GTPase Cdc42 and has been shown to regulate cell morphology and cytoskeletal organization in mammalian cells. To examine the physiological and developmental functions of PAK4, we have disrupted the PAK4 gene in mice. The absence of PAK4 led to lethality by embryonic day 11.5, a result most likely due to a defect in the fetal heart. Striking abnormalities were also evident in the nervous systems of PAK4-deficient embryos. These embryos had dramatic defects in neuronal development and axonal outgrowth. In particular, spinal cord motor neurons and interneurons failed to differentiate and migrate to their proper positions. This is probably related to the role for PAK4 in the regulation of cytoskeletal organization and cell and/or extracellular matrix adhesion. PAK4-null embryos also had defects in proper folding of the caudal portion of the neural tube, suggesting an important role for PAK4 in neural tube development.

The changing epidemiology of acute and subacute haematogenous osteomyelitis in children.

We have reviewed the incidence of bacteriologically or radiologically confirmed acute haematogenous osteomyelitis in children under 13 years of age resident in the area of the Greater Glasgow Health Board between 1990 and 1997. In this period there was a fall of 44% in the incidence of both acute and subacute osteomyelitis, mainly involving the acute form (p = 0.005). This mirrors the decline of just over 50% previously reported in the same population between 1970 and 1990. Using multiple regression analysis a decline in incidence of 0.185 cases per 100,000 population per year was calculated for the 28-year period (p < 0.001). Staphylococcus was the most commonly isolated pathogen (70%). Only 20% of patients required surgery and there was a low rate of complications (10%). In general, patients with a subacute presentation followed a benign course and there were no complications or long-term sequelae in this group. Haematogenous osteomyelitis in children in this area is becoming a rare disease with an annual incidence of 2.9 new cases per 100,000 population per year.

Leg lengthening for short stature in Turner's syndrome.

We describe ten patients with Turner's syndrome (karyotype 45, XO) who had leg lengthening for short stature. A high incidence of postoperative complications was encountered and many patients required intramedullary fixation as a salvage procedure. We discuss the reasons for this and highlight the differences between our findings and those of a similar series recently reported. In view of the considerable difficulties encountered, we do not recommend leg lengthening in Turner's syndrome.

Telecommunication interventions for caregivers of elders with dementia.

Caregiver Interventions via Telecommunications (CIT) is designed for family caregivers of elders with dementia. Building on Riegel's dialectical theory of human development, the authors argue that psychotherapeutic interventions, made highly accessible by telecommunication technology, assist caregivers to achieve positive developmental outcomes. Specific components of CIT are described, and an outline for a structured protocol is provided. Advantages, disadvantages, and future directions of telecommunications therapy are discussed.

The orthopaedic implications of peripheral limb ischaemia in infants and children.

Peripheral limb ischaemia is rare in children. We have treated only 12 infants and children with this condition in the past 15 years at the Royal Hospital for Sick Children in Glasgow. There were nine neonates and three older children. Most were suffering from life-threatening illnesses or severe infection. Two were born with ischaemic arms with no apparent cause. We have analysed the factors leading to ischaemia, the outcome of the initial treatment and the later orthopaedic problems. Two required amputation of both legs, one of an arm, two of feet and one of toes. Two had skin grafts. All surgery was performed after demarcation was well established and delayed closure was used after amputation. Five children developed limb-length discrepancy or an angular deformity. To date two have required additional corrective surgery.

Cloning, sequencing, and expression of clustered genes encoding beta-hydroxybutyryl-coenzyme A (CoA) dehydrogenase, crotonase, and butyryl-CoA dehydrogenase from Clostridium acetobutylicum ATCC 824.

The enzymes beta-hydroxybutyryl-coenzyme A (CoA) dehydrogenase (BHBD), crotonase, and butyryl-CoA dehydrogenase (BCD) from Clostridium acetobutylicum are responsible for the formation of butyryl-CoA from acetoacetyl-CoA. These enzymes are essential to both acid formation and solvent formation by clostridia. Clustered genes encoding BHBD, crotonase, BCD, and putative electron transfer flavoprotein alpha and beta subunits have been cloned and sequenced. The nucleotide sequence of the crt gene indicates that it encodes crotonase, a protein with 261 amino acid residues and a calculated molecular mass of 28.2 kDa; the hbd gene encodes BHBD, with 282 residues and a molecular mass of 30.5 kDa. Three open reading frames (bcd, etfB, and etfA) are located between crt and hbd. The nucleotide sequence of bcd indicates that it encodes BCD, which consists of 379 amino acid residues and has high levels of homology with various acyl-CoA dehydrogenases. Open reading frames etfB and etfA, located downstream of bcd, encode 27.2- and 36.1-kDa proteins, respectively, and show homology with the fixAB genes and the alpha and beta subunits of the electron transfer flavoprotein. These findings suggest that BCD in clostridia might interact with the electron transfer flavoprotein in its redox function. Primer extension analysis identified a promoter consensus sequence upstream of the crt gene, suggesting that the clustered genes are transcribed as a transcriptional unit and form a BCS (butyryl-CoA synthesis) operon. A DNA fragment containing the entire BCS operon was subcloned into an Escherichia coli-C. acetobutylicum shuttle vector. Enzyme activity assays showed that crotonase and BHBD were highly overproduced in cell extracts from E. coli harboring the subclone. In C. acetobutylicum harboring the subclone, the activities of the enzymes crotonase, BHBD, and BCD were elevated.

Children's proximal phalangeal neck fractures with 180 degrees rotational deformity.

Five patients under 4 years of age with 180 degrees rotational deformity of a proximal phalangeal neck fracture are described. All cases resulted from a direct shear force to the bone coupled with a sharp withdrawal reaction of the hand. All of the children were successfully treated with open reduction and internal fixation but only after fruitless attempts at closed manipulation and an initial lack of recognition of the severity of the fracture. Each child achieved a full functional recovery of the finger with clinical and radiological union at 4 weeks.

Symptomatic cortical irregularities of the distal femur simulating malignancy.

We reviewed the records and radiographs of seven children who presented with knee pain, local tenderness over the medial femoral condyle, and radiological irregularity of the distal medial metaphysis of the femur suggestive of malignancy. In the five patients who had biopsies, histological changes were consistent with musculotendinous avulsion, and the dissection of ten cadavers confirmed the site to be the insertion of part of the adductor magnus. The recognition of this lesion and knowledge of its benign nature may avoid unnecessary anxiety and needless biopsy.