Langerhans cell histiocytosis: 23 years' paediatric experience highlights severe long-term sequelae.

PURPOSE: To review the presentation and outcome of patients with Langerhans cell histiocytosis attending The Royal Hospital for Sick Children, Glasgow over a 23-year period. METHOD: Thirty-one children were diagnosed with Langerhans cell histiocytosis between January 1990 and December 2012. Retrospective information from medical records was gathered on age at diagnosis, presenting symptoms, classification of disease, treatment and long-term outcome. RESULTS: There were 17 boys and 14 girls; median age at diagnosis 2 years 9 months (interquartile range: 1 year 6 months to 4 years 4 months). Eleven were below 2 years and two were below 6 months of age at diagnosis. Eighteen (58%) children had single system disease of which four were multifocal; 13 (42%) had multisystem disease. Seventeen children improved with conservative treatment. Fourteen required steroids and dual agent chemotherapy; three required further chemotherapy. One child died. Two children had successfully treated relapses. Ten developed diabetes insipidus, seven were growth hormone deficient, two suffered from hypothyroidism and one panhypopituitarism. Median follow-up of the cohort was 8 years 10 months (interquartile range: 5 years 5 months to 12 years 7 months). CONCLUSION: Langerhans cell histiocytosis is a rare disease in infants and young children, with a variable course ranging from self-limiting to life threatening. In very young children (under 2 years of age), multisystem disease is more common, requiring intensive chemotherapy and lifelong follow-up. Lasting sequelae were identified in over a third of patients, including endocrine dysfunction, hearing difficulties, neurological and psychological problems.

Language and social/emotional problems identified at a universal developmental assessment at 30 months.

BACKGROUND: Preschool language and neurodevelopmental problems often persist and impede learning. The aims of the current study are to assess the uptake of a new universal 30 month health visitor contact and to quantify the prevalence of language delay and social/emotional difficulties. METHODS: All families of 30 month old children in four Glasgow localities were offered a visit from their health visitor. Structured data were collected relating to language, social and emotional development using three instruments; The Strengths and Difficulties Questionnaire (SDQ), the abbreviated Sure Start Language Measure and a two-item language screen. RESULTS: From an eligible population of 543 children, there was a 90% return rate of contact forms from the health visitors, and assessments were completed on 78% of eligible children. Visit completion rates did not differ significantly by socio-economic status. 3-8% of children were reported to have language delay depending on the method of assessment. 8.8% of children scored in the "abnormal" range of SDQ total difficulties scores and 31.1% had an abnormality in at least one subscale. There was substantial overlap between language delay and abnormal scores on the SDQ. CONCLUSIONS: Universal assessment of neurodevelopmental function at 30 months identified a significant proportion of children, including those previously considered at low risk, with both language and social/emotional difficulties. Further work is required to assess the precise nature of these difficulties and to assess the potential impact on services.

Prevalence of reactive attachment disorder in a deprived population.

BACKGROUND: Reactive attachment disorder (RAD) is associated with early childhood maltreatment and has unknown population prevalence beyond infancy. AIMS: To estimate RAD prevalence in a deprived population of children. METHOD: All 1646 children aged 6-8 years old in a deprived sector of an urban UK centre were screened for RAD symptoms. Parents of high and low scorers were interviewed using semi-structured interviews probing for psychopathology and individuals likely to have RAD were offered face-to-face assessment. RESULTS: Questionnaire data were available from 92.8% of teachers and 65.8% of parents. Assessments were conducted with 50% of those invited and missing data were imputed--based on the baseline data--for the rest. We calculated that there would be 23 children with definite RAD diagnoses, suggesting that the prevalence of RAD in this population was 1.40% (95% CI 0.94-2.10). CONCLUSIONS: In this deprived general population, RAD was not rare.

Agreement of accelerometer and a physical activity questionnaire in adults with intellectual disabilities.

PURPOSE: To assess the level of agreement between accelerometer and proxy-respondent questionnaire measurement of the physical activity levels of adults with intellectual disabilities. METHODS: In Glasgow, U.K., from May to September 2009, the main carer of participants with intellectual disabilities was asked to complete the International Physical Activity Questionnaire-Short Version, detailing the participants' regular physical activity levels. Participants were also invited to wear an ActiGraph GT1M accelerometer for seven consecutive days, during all waking hours. The level of agreement from the two measurements was compared using the Bland-Altman method. RESULTS: There is limited agreement between physical activity and sedentary behavior measured with accelerometer and proxy-respondent questionnaire. The 95% limits of agreement for both moderate activity and sedentary activity were -44.48 to 34.20 min per day and -8.41 to 6.79 h per day, respectively. As physical activity increased above 10 min per day, the agreement between the accelerometer and International Physical Activity Questionnaire-Short Version data decreased further. CONCLUSION: It remains uncertain whether questionnaire methods have sufficient reliability for use in surveillance of physical activity levels of adults with intellectual disabilities.

An open study of the effectiveness of a multi-component weight-loss intervention for adults with intellectual disabilities and obesity.

Adults with intellectual disabilities experience high rates of obesity. Despite this higher risk, there is little evidence on the effectiveness of weight-loss interventions for adults with intellectual disabilities and obesity. The present study examined the effectiveness of the TAKE 5 multi-component weight-loss intervention. Adults with obesity were invited using specialist intellectual disability services to participate in the study. Obesity was defined as a BMI of 30 kg/m2 or greater. TAKE 5 included a daily energy-deficit diet of 2510 kJ (600 kcal), achieved via a personalised dietary prescription. Participants' body weight, BMI, waist circumference and levels of physical activity and sedentary behaviour were measured before and after the intervention. A total of fifty-four individuals consented to participate, of which forty-seven (87 %) completed the intervention in the study period. There was a significant decrease in body weight (mean difference - 4·47 (95 % CI - 5·91, - 3·03) kg; P < 0·0001), BMI (- 1·82 (95 % CI - 2·36, - 1·29) kg/m(2); P < 0·0001), waist circumference (- 6·29 (95 % CI - 7·85, - 4·73) cm; P < 0·0001) and daily sedentary behaviour of participants (- 41·40 (95 % CI - 62·45, - 20·35) min; P = 0·00 034). Of the participants who completed the intervention, seventeen (36·2 %) lost 5 % or more of their initial body weight. Findings from the study suggest that TAKE 5 is an effective weight-loss intervention for adults with intellectual disabilities and obesity. The effectiveness of TAKE 5 should be examined further in a controlled study.

Linking international agricultural research knowledge with action for sustainable development.

We applied an innovation framework to sustainable livestock development research projects in Africa and Asia. The focus of these projects ranged from pastoral systems to poverty and ecosystems services mapping to market access by the poor to fodder and natural resource management to livestock parasite drug resistance. We found that these projects closed gaps between knowledge and action by combining different kinds of knowledge, learning, and boundary spanning approaches; by providing all partners with the same opportunities; and by building the capacity of all partners to innovate and communicate.

Practical three color live cell imaging by widefield microscopy.

Live cell fluorescence microscopy using fluorescent protein tags derived from jellyfish and coral species has been a successful tool to image proteins and dynamics in many species. Multi-colored aequorea fluorescent protein (AFP) derivatives allow investigators to observe multiple proteins simultaneously, but overlapping spectral properties sometimes require the use of sophisticated and expensive microscopes. Here, we show that the aequorea coerulescens fluorescent protein derivative, PS-CFP2 has excellent practical properties as a blue fluorophore that are distinct from green or red fluorescent proteins and can be imaged with standard filter sets on a widefield microscope. We also find that by widefield illumination in live cells, that PS-CFP2 is very photostable. When fused to proteins that form concentrated puncta in either the cytoplasm or nucleus, PSCFP2 fusions do not artifactually interact with other AFP fusion proteins, even at very high levels of over-expression. PSCFP2 is therefore a good blue fluorophore for distinct three color imaging along with eGFP and mRFP using a relatively simple and inexpensive microscope.

Biochemical activities of the absA two-component system of Streptomyces coelicolor.

The AbsA1 sensor kinase and its cognate response regulator AbsA2 are important regulators of antibiotic synthesis in Streptomyces coelicolor. While certain point mutations in absA1 reduce or eliminate the synthesis of several antibiotics, null mutations in these genes bring about enhanced antibiotic synthesis. We show here that AbsA1, which is unusual in sequence and structure, is both an AbsA2 kinase and an AbsA2 approximately P phosphatase. The half-life of AbsA2 approximately P in solution is 68.6 min, consistent with a role in maintaining a relatively stable state of transcriptional repression or activation. We find that mutations in the absA locus that enhance antibiotic synthesis impair AbsA2 kinase activity and that mutations that repress antibiotic synthesis impair AbsA2 approximately P phosphatase activity. These results support a model in which the phosphorylation state of AbsA2 is determined by the balance of the kinase and phosphatase activities of AbsA1 and where AbsA2 approximately P represses antibiotic biosynthetic genes either directly or indirectly.

An evaluation of economics and acceptability of screening for Chlamydia trachomatis infection, in women attending antenatal, abortion, colposcopy and family planning clinics in Scotland, UK.

OBJECTIVE: The aims of this study were to determine cost effectiveness of screening for Chlamydia trachomatis in hospital-based antenatal and gynaecology clinics, and community-based family planning clinics. Additionally, women's views of screening were determined in the hospital-based clinics. DESIGN: Cost effectiveness based on decision model. Model probabilities were generated for a hypothetical sample of 250 women in each age group in each setting, based on prevalence studies, published data and expert opinion. A prospective observational study was used to generate data on prevalence and acceptability. SETTING: Antenatal, gynaecology and family planning clinics in Aberdeen, Edinburgh and Glasgow. SAMPLE: Prevalence was estimated in 2817 women. Acceptability was determined in 484 women. METHODS: An economic evaluation was performed using prevalence data from this and a previous study, and using outcome data from the literature and observational work. Incremental cost effectiveness ratios were estimated for each age group and clinical setting. Sensitivity analyses were performed to determine the robustness of incremental cost effectiveness ratios to changes in the incidence of long term sequelae and costs. The prevalence of infection was determined by nucleic acid amplification of urine samples or endocervical swabs. Knowledge of C. trachomatis and women's views of screening were determined using structured questionnaires. MAIN OUTCOME MEASURES: Direct health service costs of screening, incidence and costs associated with adverse sequelae, women's views of screening and prevalence of infection. RESULTS: The estimated cost of screening 250 women in each age group in each the four sample populations (total population of 3750) is 49,367 UK pounds, while preventing 64 major sequelae. This represents a net cost of 771.36 UK pounds in preventing one major sequela. Selective screening of all women under 20 years and all patients attending abortion clinics were shown to be the most cost effective strategies. These results were relatively insensitive to changes in estimated parameters, such as uptake rate, probabilities and unit costs of all major sequelae averted. Prevalence (95% CI) of infection in the highest risk groups (those aged under 20 in both antenatal and abortion clinics) was 12.1% (8.6-16.7) and 12.7% (7.3-21.2), respectively. The majority (>95%) of women agreed with a policy of regular screening for C. trachomatis, and screening in the settings employed in this study was largely acceptable. CONCLUSIONS: A single episode of screening for C. trachomatis does not result in net cost savings. Currently recommended strategies of screening for C. trachomatis in women under 25 years of age in abortion clinics are supported by our data on prevalence and acceptability. These data also suggest that hospital-based screening strategies should be further extended to include younger women attending antenatal clinics and all women of reproductive age attending colposcopy clinics.

Parallel observation of four methods for screening women under 25 years of age for genital infection with Chlamydia trachomatis.

OBJECTIVES: To compare four methods of screening women for Chlamydia trachomatis in an obstetrics and gynaecology department. STUDY DESIGN: A total of 303 healthy women under 25 years were recruited from antenatal, induced abortion, and family planning clinics. Each underwent parallel testing of endocervical specimens by enzyme immunoassay (EIA) and ligase chain reaction (LCR), vulval swabs by LCR, and urine by LCR. Outcome measures included sensitivity, specificity, acceptability of each method, and the influence of pregnancy. RESULTS: Overall prevalence (95% CI) was 9.9% (6.8-14%). All methods had a high rate of detection (75-100%), not affected by pregnancy. Urine was most acceptable, followed by vulval swabbing. CONCLUSIONS: Opportunistic screening of women under 25 years attending obstetric and gynaecology affiliated clinics found high rates of C. trachomatis infection. Both urine and vulval swab methods were highly sensitive, acceptable, and not affected by pregnancy status. Due to pragmatic issues surrounding the urine method, screening by vulval swabs deserves wider recognition.

Chlamydia trachomatis in subfertile women undergoing uterine instrumentation. The clinician's role.

Most women attending a fertility clinic will undergo uterine instrumentation either diagnostically and/or therapeutically. This places them at potential risk of chlamydial pelvic inflammatory disease. Clinicians remain unclear about the roles of screening, serology and prophylactic antibiotics. A review of the evidence suggests that women <25 years and those older with risk factors, men with risk factors and gamete donors should have their lower genital tract screened for Chlamydia trachomatis by a sensitive test. More information is required before screening men by age can be recommended. Serology in its present form cannot be advocated as a screening tool. Those women with a past history of chlamydial morbidity or a diagnosis of tubal pathology should, in addition to screening, be covered with prophylactic antibiotics when undergoing uterine instrumentation. The partner should be screened for sexually transmitted infections. Non-selective use of prophylactic antibiotics serves only to increase the problem of antibiotic resistance and maintain the bacterial load of chlamydia in the community.

StoPK-1, a serine/threonine protein kinase from the glycopeptide antibiotic producer Streptomyces toyocaensis NRRL 15009, affects oxidative stress response.

The glycopeptide antibiotic-producing bacterium, Streptomyces toyocaensis NRRL 15009, has proteins phosphorylated on Ser, Thr, Tyr and His, implying the presence of a battery of associated kinases. We have identified the Ser/Thr protein kinase gene fragments stoPK-1, stoPK-2, stoPK-3 and stoPK-4 from S. toyocaensis NRRL 15009 by a polymerase chain reaction (PCR) strategy using oligonucleotide primers based on eukaryotic Ser/Thr and Tyr kinase sequences. One of these (stoPK-1) was subsequently cloned in its entirety from a 3.2 kb genomic BamHI fragment. stoPK-1 encodes a 642-amino-acid protein with a predicted N-terminal Ser/Thr kinase domain and a C-terminal coiled-coil region divided by a membrane-spanning region. Expression of StoPK-1 in Escherichia coli yielded a protein confined to the membrane fraction, which was found to be phosphorylated exclusively on Thr residues and could transfer phosphate to the model substrates myelin basic protein and histone H1. Both autophosphorylation and phosphoryl transfer could be inhibited by the flavanoid apigenin. Disruption of stoPK-1 with the apramycin resistance gene in the S. toyo-caensis chromosome resulted in changes in mycelial morphology and an increased sensitivity to the redox cycling agents paraquat and nitrofurantoin on glucose-containing media. Supplying stoPK-1 or the S. coelicolor homologue pkaF in trans could reverse this sensitivity, whereas a catalytically inactive mutant of stoPK-1 could not, indicating that kinase activity is essential for this phenotype. This suggests a link between this membrane-bound protein kinase in signalling pathways sensitive to oxidative stress and/or glucose metabolism. These results broaden the roles of Ser/Thr protein kinases in bacteria and underscore the diversity of signal transduction mechanisms available to respond to various stimuli.