Social Media and Website Use: The Experiences of Parents and Carers Accessing Care at the Oxford Craniofacial Unit.

Introduction: Historically, medical professionals have been the providers of specialist information about rare medical conditions. Now, increasingly, patients and the public are using the internet to access and generate information about medical diagnoses. The global nature of the internet allows patients to connect across geographical borders, and to obtain and share information that would have been previously inaccessible to them.

The role of the clinical psychologist within a cleft service.

Clinical psychologists are core members of UK cleft services. This paper outlines the variety of ways in which clinical psychologists work across the lifespan to promote the psychological wellbeing of those born with a cleft and their families. In the context of dental or orthodontic treatment, this involves a combination of early intervention and advice, psychological assessment or specialist psychological therapy for individuals experiencing dental anxiety or anxiety regarding the appearance of their teeth.

PARP1-MGMT complex underpins pathway crosstalk in O-methylguanine repair.

DNA lesions induced by alkylating agents are repaired by two canonical mechanisms, base excision repair dependent on poly(ADP) ribose polymerase 1 (PARP1) and the other mediated by O-methylguanine (OmeG)-DNA methyltransferase (MGMT) in a single-step catalysis of alkyl-group removal. OmeG is the most cytotoxic and mutagenic lesion among the methyl adducts induced by alkylating agents. Although it can accomplish the dealkylation reaction all by itself as a single protein without associating with other repair proteins, evidence is accumulating that MGMT can form complexes with repair proteins and is highly regulated by a variety of post-translational modifications, such as phosphorylation, ubiquitination, and others.

Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function.

Mitochondrial dysfunction is a key driver of diabetes and other metabolic diseases. Mitochondrial redox state is highly impactful to metabolic function but the mechanism driving this is unclear. We generated a transgenic mouse which overexpressed the redox enzyme Thioredoxin Reductase 2 (TrxR2), the rate limiting enzyme in the mitochondrial thioredoxin system.

Nanoformulation of Talazoparib Increases Maximum Tolerated Doses in Combination With Temozolomide for Treatment of Ewing Sarcoma.

The Pediatric Preclinical Testing Program previously identified the PARP inhibitor talazoparib (TLZ) as a means to potentiate temozolomide (TMZ) activity for the treatment of Ewing sarcoma. However, the combination of TLZ and TMZ has been toxic in both preclinical and clinical testing, necessitating TMZ dose reduction to ~15% of the single agent maximum tolerated dose. We have synthesized a nanoparticle formulation of talazoparib (NanoTLZ) to be administered intravenously in an effort to modulate the toxicity profile of this combination treatment.

Dual targeting of androgen receptor and mTORC1 by salinomycin in prostate cancer.

Androgen receptor (AR) and PI3K/AKT/mTORC1 are major survival signals that drive prostate cancer to a lethal disease. Reciprocal activation of these oncogenic pathways from negative cross talks contributes to low/limited success of pathway-selective inhibitors in curbing prostate cancer progression. We report that the antibiotic salinomycin, a cancer stem cell blocker, is a dual-acting AR and mTORC1 inhibitor, inhibiting PTEN-deficient castration-sensitive and castration-resistant prostate cancer in culture and xenograft tumors.

Brief Assessment of Parental Perception (BAPP): Development and validation of a new measure for assessing paediatric outcomes after bilateral cochlear implantation.

Objective: In contrast to previous clinical practice, current guidelines recommend bilateral cochlear implantation in children, resulting in a cohort of children who initially received one implant, but have subsequently had a second, contralateral implant. This study aimed to explore satisfaction and quality of life in children implanted simultaneously or sequentially.

Design: A novel measure of satisfaction and quality of life following paediatric bilateral cochlear implantation (the Brief Assessment of Parental Perception; BAPP) was developed and preliminary validation undertaken as part of a large, national project of bilateral implantation.

Normothermic ex vivo perfusion provides superior organ preservation and enables viability assessment of hearts from DCD donors.

The shortage of donors in cardiac transplantation may be alleviated by the use of allografts from donation after circulatory death (DCD) donors. We have previously shown that hearts exposed to 30 min warm ischemic time and then flushed with Celsior supplemented with agents that activate ischemic postconditioning pathways, show complete recovery on a blood-perfused ex vivo working heart apparatus. In this study, these findings were assessed in a porcine orthotopic heart transplant model.

Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions.

Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e.

Involving young people in decision making about sequential cochlear implantation.

Background: The National Institute for Health and Clinical Excellence guidelines recommended young people who currently have one cochlear implant be offered assessment for a second, sequential implant, due to the reported improvements in sound localization and speech perception in noise. The possibility and benefits of group information and counselling assessments were considered. Previous research has shown advantages of group sessions involving young people and their families and such groups which also allow young people opportunity to discuss their concerns separately to their parents/guardians are found to be 'hugely important'.

Good practice guidelines for clinical psychologists working in paediatric cochlear implant teams.

There are relatively few clinical psychologists working in paediatric cochlear implant centres in the UK and in this respect we lag behind other countries such as the USA and The Netherlands. In an effort to promote the added value our profession can offer teams, the clinical psychologists working in paediatric CI centres have put together good practice guidelines. This article outlines the rationale for putting together the guidelines, highlights the unique contribution clinical psychologists can offer, outlines the evidence base for psychological input in this clinical population, and offers a fictional case study for illustration.

Adolescents' experiences of receiving and living with sequential cochlear implants: an interpretative phenomenological analysis.

There is currently a unique opportunity to examine the experiences of young people who receive a second sequential cochlear implant (SCI), after only having had 1 cochlear implant (CI) for most of their lives. Eleven young people who had opted to receive an SCI were interviewed. Interpretative phenomenological analysis resulted in the identification of 6 master themes.

Factors associated with a difficult induction of general anaesthesia.

Background: Many children experiencing a procedure under general anaesthetic (GA), including those having surgery for cochlear implantation, display behaviours indicative of distress during induction of anaesthesia. It would be useful to ascertain which factors in the pre-operative period are related to the presence of distress at induction in order to target appropriate psychological preparation.

Methods: The families of 84 children aged 4-7 years undergoing a procedure under GA (including insertion of a cochlear implant) completed three questionnaires assessing temperament, behavioural difficulties, and pre-operative worries.

A pilot study of core stability and athletic performance: is there a relationship?

Study Design: Correlation study

Objectives: To objectively evaluate the relationship between core stability and athletic performance measures in male and female collegiate athletes.

Background: The relationship between core stability and athletic performance has yet to be quantified in the available literature. The current literature does not demonstrate whether or not core strength relates to functional performance.

Developmental expression of Toll-like receptors-2 and -4 in preterm baboon lung.

Preterm babies are susceptible to respiratory infection due to immature lung and immune system. Immune cells express Toll-like receptors (TLRs), which may be important in local host defense of preterm infants. We studied the expression of TLR2 and TLR4 in lung tissues of fetal baboons delivered at 125, 140, and 175 days of gestation (dGA; term=185+/-2 days) and preterm baboons that became naturally infected with bacterial/fungal pathogens.

Use of extracorporeal membrane oxygenation as a bridge to primary lung transplant: 3 consecutive, successful cases and a review of the literature.

Many transplant centers have considered extracorporeal membrane oxygenation (ECMO) to be a contraindication to lung transplantation, due to historically poor outcomes. However, recent advances in the technical aspects of ECMO have enabled patients to be supported with relative safety for several weeks until a donor lung becomes available. We present 3 young patients with acute (in 1 case, acute on chronic), severe respiratory failure that was refractory to conventional ventilation, who were placed on venovenous ECMO.

Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young.

Aims/hypothesis: Heterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY. Genomic deletions of the HNF1B (also known as TCF2) gene have recently been shown to account for one third of mutations causing renal cysts and diabetes syndrome. We investigated the prevalence of partial and whole gene deletions in UK patients meeting clinical criteria for GCK or HNF-1alpha/-4alpha MODY and in whom no mutation had been identified by sequence analysis.

Why don't all whales have cancer? A novel hypothesis resolving Peto's paradox.

Larger organisms have more potentially carcinogenic cells, tend to live longer and require more ontogenic cell divisions. Therefore, intuitively one might expect cancer incidence to scale with body size. Evidence from mammals, however, suggests that the cancer risk does not correlate with body size.

Does amethocaine gel influence blood results obtained from capillary sampling?

Unlabelled: In many children routine blood samples are obtained by capillary sampling, a technique that appears to cause high levels of pain and distress in the child. Topical anaesthesia might alleviate the pain associated with capillary blood sampling but would it affect the blood sample?

Aim: a preliminary study to determine whether topical local anaesthetic would affect the values of commonly performed biochemical tests

Method: 22 healthy adult volunteers were recruited; each volunteer acted as his or her own control. Ametop was applied to a socially clean digit and covered with an occlusive dressing.

Immunophenotype and functions of fetal baboon bone-marrow derived dendritic cells.

Dendritic cells (DCs) are unique antigen-presenting cells that can take up pathogens, pathogens-derived and stress-antigens and stimulate antigen-specific immune response. Here we investigated the immunobiology of fetal DCs and compared their phenotype and activation status against infectious stimuli with those of young and adult baboons. The DCs were obtained from femoral bone-marrow (BMDCs) of fetus (140 and 175 days of gestation), young (4-5 years old) and mature adult (10-35 years old) baboons.

Childhood asthma: healthcare resource utilisation in those with and without a diagnosis of the condition.

Aim: To examine healthcare utilisation and the direct financial costs in providing medical care to a population of children aged 5-15 years with respiratory complaints. Secondarily, to assess whether these costs depended upon having specific asthma diagnosis or not.

Method: A postal respiratory questionnaire was sent to the parents or guardians of all children registered with two general practices.

Enhanced cardioprotection of the rat heart during hypothermic storage with combined Na+ - H+ exchange inhibition and ATP-dependent potassium channel activation.

Background: We investigated the ability of mitochondrial adenosine triphosphate-dependent potassium-channel activation to augment the protection of Na(+)-H(+) exchanger inhibition in isolated working rat hearts after 6 hours of hypothermic storage in an extracellular-based cardioplegic solution.

Methods: We treated hearts with the potassium-channel openers diazoxide (100 micromol/liter) or BMS-180448 (10 micromol/liter) or with the Na(+)-H(+) exchanger inhibitor cariporide (10 micromol/liter). Cariporide also was administered in combination with either diazoxide or BMS-180448 in 2 other treatment groups.