A5103123779- Childhood Cancer Survivors' Quality of Life
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Diabetes and associated disorders
- Diabetes Management and Research
- Genetic Neurodegenerative Diseases
- Acute Lymphoblastic Leukemia research
- Pancreatic function and diabetes
- Growth Hormone and Insulin-like Growth Factors
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Muscle Physiology and Disorders
- Sarcoma Diagnosis and Treatment
- Testicular diseases and treatments
- Obesity, Physical Activity, Diet
- Hematopoietic Stem Cell Transplantation
- Bone health and treatments
- Nutrition and Health in Aging
- Bone and Joint Diseases
- Ethics and Legal Issues in Pediatric Healthcare
- Neuroblastoma Research and Treatments
- Hypothalamic control of reproductive hormones
- Obesity and Health Practices
- Neuroendocrine Tumor Research Advances
- Neonatal Respiratory Health Research
Evelina London Children's Healthcare
2024
Guy's and St Thomas' NHS Foundation Trust
2022
St George’s University Hospitals NHS Foundation Trust
2016-2020
Bristol Royal Hospital for Children
2009-2018
University Hospitals Bristol NHS Foundation Trust
2015-2018
University of Bristol
2015-2018
Cincinnati Children's Hospital Medical Center
2015-2018
St George's Hospital
2015-2017
University of Southern California
2016-2017
St George's Hospital
2015
Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease characterized by skeletal muscle wasting, weakness, and myotonia. DM1 caused the accumulation of CUG repeats, which alter biological activities RNA-binding proteins, including CUG-binding protein (CUGBP1). CUGBP1 an important translational regulator that activated cyclin D3-dependent kinase 4 (CDK4). Here we show mutant repeats suppress Cdk4 signaling increasing stability activity glycogen synthase 3β (GSK3β). Using mouse...
Immunotherapy targeting the autoimmune process in type 1 diabetes (T1D) can delay loss of β-cells but needs to have minimal adverse effects be an adjunct insulin management T1D. Ustekinumab binds shared p40 subunit interleukin (IL)-12 and IL-23, development T helper cells 17 (T
Background Survivors of childhood acute lymphoblastic leukaemia (ALL) treated with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have a high cardiometabolic risk despite lacking overt clinical obesity. This study characterised composition using different methodologies explored associations reduced insulin sensitivities in group ALL survivors with/without HSCT/TBI. Procedure HSCT/TBI (n = 20,10 M) were compared Chemotherapy‐only 31), an obese non‐leukaemic...
Impaired glucose tolerance (IGT) and diabetes mellitus (DM) occur more frequently after bone marrow transplantation total body irradiation (BMT/TBI), but the mechanism is unclear. This study investigates insulin sensitivity, β-cell reserve pancreatic volume in adult survivors of childhood acute lymphoblastic leukaemia (ALL).Survivors (aged 16-26 years) ALL treated with BMT/TBI (10-14·4 Gy) Group 1 (n = 20, 10 m) were compared a chemotherapy-only 2 28, 11 m). Participants underwent...
Significance Inherited multisystemic diseases, myotonic dystrophies type 1 (DM1) and 2 (DM2), are caused by long CUG CCUG RNA repeats. The mutant repeats should be degraded after intron excision; however, this accumulates in cells, leading to pathology. Although RNAs may with synthetic oligonucleotides, the identification of a cause increased stability would help improve efficiency their degradation. We found that reduction helicase p68 skeletal muscle biopsies DM1 DM2 patients contributes...
Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor (CUGBP1/CELF1) and muscleblind protein. Mutant repeats elevate CUGBP1 alter activity via glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal in DM1 mice [human skeletal actin mRNA,...
Myotonic dystrophy type 2 (DM2) is a neuromuscular disease caused by an expansion of intronic CCTG repeats in the CNBP gene, which encodes protein regulating translation and transcription. To better understand role cellular nucleic acid binding (CNBP) DM2 pathology, we examined skeletal muscle new model Cnbp knockout (KO) mice. This study showed that loss disturbs myofibrillar sarcomeric organization at birth. Surviving homozygous KO mice develop atrophy young age. The phenotype heterozygous...
Myotonic dystrophy type 1 (DM1), an incurable, neuromuscular disease, is caused by the expansion of CTG repeats within 3' UTR DMPK on chromosome 19q. In DM1 patients, mutant transcripts deregulate RNA metabolism altering CUG RNA-binding proteins. Several approaches have been proposed for therapy focused specific degradation or correction proteins, affected repeats. One such protein (CUGBP1). The ability CUGBP1 to increase inhibit translation depends phosphorylation at Ser302, which mediated...
Background: Thyroid nodules are common and most benign. Previous data from our laboratory others has suggested that gene profiling can accurately distinguish between benign malignant thyroid provide new leads in the study of tumorigenesis. Current preoperative techniques do not permit distinction neoplastic hyperplastic follicular neoplasms. These studies were undertaken to determine whether tumors could be subcategorized by molecular profiling. Methods: Molecular profiles 8 adenomas...
Background To compare the impact of cognitive behavioural therapy (CBT) with non-directive supportive counselling (NDC) on glycaemic control and psychological well-being in adolescents type 1 diabetes mellitus (T1DM). Materials Methods Participants aged 11 to 16 years T1DM (duration ≥1 year) from 4 UK-based paediatric centres were randomised receive either 6 weekly sessions 1-to-1 CBT (n = 43) or NDC 42), 2 further at 12 months. Follow-up continued for months postintervention. Outcome...
Childhood cancer survivors treated with haematopoietic stem cell transplantation (HSCT) and total body irradiation are at an increased risk of developing diabetes early in life due to insulin resistance β-cell dysfunction, but the optimal screening method is unknown. The National Institute for Health Care Excellence guidelines community recommend using fasting glucose ≥ 7 mmol/l and/or HbA1c 48 mmol/mol (6.5%) diagnosis and, 5.5-6.9 or 42-47 (6-6.5%) indicate high risk. This study aimed...
ABCC8 gene mutations with different inheritance patterns have been well described to cause transient and permanent forms of neonatal diabetes onset hyperglycemia commonly before the age 6 months, rare cases between 12 months. However, recent analyses also demonstrated in patients monogenic (maturity young, MODY), milder clinical phenotypes later hyperglycemia. We report two siblings mellitus due a novel homozygous p.(Phe1068Ile) (c.3202T>A) missense mutation gene, but significantly...
Two Caucasian girls, both of normal weight and body mass indices, were diagnosed with type A insulin resistance (IR) in childhood. Case 1 presented premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, asymptomatic diabetes. Subsequent investigation revealed raised adiponectin (15.3 mg/L) heterozygous p.Pro1205Leu mutation the INSR gene encoding receptor. She experienced postprandial hypoglycaemia on metformin; acarbose was trialled discontinued...
Accurate histological diagnosis and classification of germ cell tumours (GCTs) is key to informing successful therapeutic surveillance strategy. The modern approach for yolk sac tumour (YST) highly curative. Because YST takes on a large morphological spectrum, it can be confused other GCT subtypes as well somatic carcinomas, particularly when presents in an extragonadal or metastatic setting. Currently available immunohistochemical markers are limited by suboptimal sensitivity specificity....
The probability of physical abuse (PA) is high in children with occult rib fractures. Other causes include non‐intentional trauma, post surgery and cardiopulmonary resuscitation. Bone fragility increases the risk fractures, namely metabolic bone disease prematurity (MBDP), osteogenesis imperfecta, rickets rare diseases. ‘Occult fractures have a abuse’ This case series describes 61 under two years age associations clinical radiological features aetiology. There were 20 cases PA, 11 surgical...
Objective Familial hypercholesterolaemia (FH) elevates low-density lipoprotein cholesterol (LDL-C) and increases cardiovascular disease (CVD) risk. This study aimed to provide evidence for the feasibility of conducting a randomised controlled trial evaluate efficacy an intervention designed improve diet physical activity in families with FH. Design A parallel, randomised, waitlist-controlled, pilot trial. Setting Three outpatient lipid clinics UK. Participants Families that comprised...
<b><i>Background:</i></b> Survivors of childhood with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have an increased cardiometabolic risk without overt obesity. <b><i>Aim:</i></b> To describe in HSCT/TBI survivors identify anthropometric measurements adiposity representative risks survivors. <b><i>Method:</i></b> Childhood leukaemia treated (<i>n</i> = 21, 11 males) were...
We undertook a feasibility study to reassess metabolic outcomes in young people with early onset obesity who attended hospital-based lifestyle weight-loss intervention during adolescence. Comparisons of assessments, including body mass index standard deviation scores (BMI–SDSs), blood pressure (BP), oral glucose tolerance tests (OGTTs), lipid profile, and alanine transaminase (ALT), before after treatment were made. Twenty-five subjects (10 males) median ages (interquartile range, IQR) 14.5...