Engineering of Rieske dioxygenase variants with improved cis-dihydroxylation activity for benzoates.

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high-value compounds, due to their capacity to perform the cis-dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis-dihydroxylation of benzoates.

Effect of oxandrolone and timing of pubertal induction on final height in Turner syndrome: final analysis of the UK randomised placebo-controlled trial.

The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and delaying ethinylestradiol induction of puberty by 2 years from 12 (E12) to 14 (E14) years in growth hormone-treated girls with TS.

Testosterone therapy and cancer risk.

Objective: To determine if testosterone therapy (TT) status modifies a man's risk of cancer.

Patients And Methods: The Urology clinic hormone database was queried for all men with a serum testosterone level and charts examined to determine TT status. Patient records were linked to the Texas Cancer Registry to determine the incidence of cancer.

Dynamics of continental accretion.

Subduction zones become congested when they try to consume buoyant, exotic crust. The accretionary mountain belts (orogens) that form at these convergent plate margins have been the principal sites of lateral continental growth through Earth's history. Modern examples of accretionary margins are the North American Cordilleras and southwest Pacific subduction zones.

Increased risk of cancer among azoospermic men.

Objective: To determine whether men with azoospermia are at an elevated risk of developing cancer in the years following an infertility evaluation.

Design: Cohort study.

Setting: United States andrology clinic.

Distress signals. Asking these tough questions will help boards to head off potential crises.

To look beyond financial metrics when assessing hospital performance, trustees should ask questions in key areas.

Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial.

Objective: To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner's syndrome receiving a standard dose of growth hormone.

Design: Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals.

Torque removal force for osseointegrated implants--two experimental studies.

Objective: To introduce a rabbit-based model for testing the torque removal force (TRF) of implants and to compare the TRF of a series of titanium implants.

Methods: Two experiments were performed at the University of the Witwatersrand. In the first, a Swedish- (SSM-N) or a South African-manufactured (SSM-S) implant was implanted into the tibiae of 12 rabbits and the TRF measured at 1, 3 and 6 months.

Fetal programming of body dimensions and percentage body fat measured in prepubertal children with a 4-component model of body composition, dual-energy X-ray absorptiometry, deuterium dilution, densitometry, and skinfold thicknesses.

Background: Intrauterine programming of body composition [percentage body fat (%BF)] has been sparsely examined with multiple independent reference techniques in children. The effects on and consequences of body build (dimensions, mass, and length of body segments) are unclear.

Objective: The study examined whether percentage fat and relation of percentage fat to body mass index (BMI; in kg/m2) in prepubertal children are programmed during intrauterine development and are dependent on body build.

Increasing body weight predicts the earlier onset of insulin-dependant diabetes in childhood: testing the 'accelerator hypothesis' (2).

Aims And Methods: It has recently been hypothesized that weight gain in childhood accelerates the onset of Type 1 diabetes, as well as increasing its risk, and that Type 1 diabetes and Type 2 diabetes may be one and the same disorder of insulin resistance. An explanation is needed for the rising incidence of childhood diabetes and, to test the Accelerator Hypothesis, we examined the anthropometric measurements recorded from birth in 168 young people presenting with Type 1 diabetes between 1980 and 2002. Pre-onset as well as peri- and post-onset measurements of height and weight were available, and waist circumference was recorded at various intervals after onset.

Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing's syndrome due to primary nodular adrenocortical hyperplasia.

Background: Primary nodular adrenocortical hyperplasia (PNAH) is a well recognized, but infrequently studied cause of paediatric Cushing's syndrome (CS).

Objective: To assess presentation, diagnosis, radiological imaging, treatment and molecular analysis of patients with childhood-onset CS due to PNAH.

Patients: Four males and two females (median age 12.

An assessment of pancreatic endocrine function and insulin sensitivity in patients with transient neonatal diabetes in remission.

Aims: To examine derived indices of beta cell function, peripheral insulin sensitivity, and the pancreatic response to intravenous glucose loading in children with a previous history of transient neonatal diabetes currently in remission, repeated after a period of two or more years.

Methods: The standard intravenous glucose tolerance test (IVGTT) was used to measure the first phase insulin response (FPIR) cumulatively at one and three minutes. In addition, fasting insulin and glucose values were used to estimate insulinogenic indices (beta cell function) and QUICKI (insulin sensitivity).

Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor.

Objective: We wished to ascertain whether mutations in the TSH receptor (TSHR) gene were present in two siblings with congenital hypothyroidism with no parental consanguinity.

Design: The pituitary-thyroid axis and thyroid gland morphology were investigated in both affected siblings and their parents. The TSHR gene was analysed in each subject.

Personality functioning: the influence of stature.

Background: The Wessex Growth Study has monitored the psychological development of a large cohort of short normal and average height control participants since school entry.

Aims: To examine the effect of stature on their personality functioning now that they are aged 18-20 years.

Methods: This report contains data from 48 short normal and 66 control participants.

Diabetes care in childhood and adolescence.

The presentation of diabetes in young people has changed significantly over recent years. Not only has there been a rising incidence of Type 1 diabetes, especially in young children, but also there is an increasing recognition of Type 2 diabetes. Young people are also increasingly being diagnosed with genetic defects of B-cell function and with diabetes in association with cystic fibrosis and other chronic diseases.

Pancreatic exocrine insufficiency and type 1 diabetes mellitus.

Studies in adults suggest that some patients with type 1 diabetes mellitus have pancreatic exocrine insufficiency (PEI). The primary aim of this study was to explore the association between pancreatic exocrine function and type 1 diabetes in young people under 17 years. The secondary aim was to evaluate the relationship between PEI in patients with diabetes, their clinical symptoms and blood glucose control.