Wimpole Timings study.

Introduction Studies show that changes to dental incentive structures and treatment timings impact behaviour among UK general dental practitioners (GDP). Since 1980, the British Dental Association (BDA) has conducted panel inquiries to understand the time taken to complete dental treatments, the most recent of these being the 1999 Heathrow Timings study.Aims Given significant changes to the UK general dental service (GDS) since 1999, this research aims to gain a refreshed understanding of the time involved to complete clinical treatments in the UK and gain insight into working hours.Materials and methods This study adopted a mixed-method research design, adapted from the BDA's Heathrow Timings study. Averages for 34 adult and 12 children's treatments were found using an online survey and group discussion with 15 GDPs.Results Overall, GDPs worked 35.23 hours per week, at an hourly rate of £39.94. Comparison to the Heathrow study in 1999 shows an increase in time to deliver multiple treatments, including clinical examinations, root canals, extractions, composite fillings, porcelain veneers, acrylic full dentures and children's extractions.Conclusion Overall, this study provides a current and updated insight into dental treatment times performed by GDPs in the UK and highlights a decrease in working hours and real-term earnings of GDPs over the past 20 years.

Case report: Effectiveness of low-dose methotrexate monotherapy in post-essential thrombocythemia myelofibrosis.

JAK/STAT pathway signalling is associated with both chronic inflammatory conditions such as psoriasis and haematological malignancies such as the myeloproliferative neoplasms (MPNs). Here we describe a 73yo female patient with a history of chronic plaque psoriasis, post-essential thrombocythemia myelofibrosis (MF) and a quality of life substantially impacted by both conditions. We report that 15 mg oral Methotrexate (MTX) weekly as a monotherapy is well tolerated, provides a substantial clinical improvement for both conditions and significantly improves quality of life. We suggest that the recently identified mechanism of action of MTX as a JAK inhibitor is likely to explain this efficacy and suggest that repurposing MTX for MPNs may represent a clinical- and cost-effective therapeutic option.

Student debt of UK dental students and recent graduates.

Introduction Studies conducted in 2013 estimated the total average debt of UK dental students in their final year. Student tuition fees in the UK have increased over time and maintenance grants abolished. With the current landscape changing, it's important to understand the effect on dental students and the current total debt upon graduation.Aims Quantify the level of debt among dental students graduating in 2021/2022 and the two years prior, understand the impact of debt, and investigate socioeconomic differences.Materials and methods An online survey with final year UK dental students and recent graduates was conducted, resulting in 103 valid responses. The survey design was adapted from a validated British Dental Association (BDA) survey conducted in 2013.Results The mean total debt among respondents was £52,922.12, a substantial increase compared to the BDA data reported in 2013, with commercial and informal loans doubling from 2013 to 2022. Three-in-five (60.2%) experienced financial difficulties during their studies. Significant differences were found among socioeconomic groups.Conclusion Findings from this study show that dental student debt continues to grow, having detrimental impacts on students and their studies, specifically those from lower income households. Interventions should focus on addressing these issues.

Contract reform - the BDA's view.

The imposition of the 2006 Units of Dental Activity contract remains a significant source of anger for the dental profession, which is perhaps only surpassed by the fact that, 16 years on, a reformed contract is yet to be delivered. After many years of piloting and prototyping and a more than year-long process to deliver marginal changes, the profession and patients clearly now need ambitious and urgent reform.This does not mean that there are simple answers - the redesign of any healthcare system is profoundly complex - but these complexities must be approached with a concerted and determined effort to bring about change as rapidly as possible.

Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD.

CONTEXT: The genetic basis of human sex development is slowly being elucidated, and >40 different genetic causes of differences (or disorders) of sex development (DSDs) have now been reported. However, reaching a specific diagnosis using traditional approaches can be difficult, especially in adults where limited biochemical data may be available. OBJECTIVE: We used a targeted next-generation sequencing approach to analyze known and candidate genes for DSDs in individuals with no specific molecular diagnosis. PARTICIPANTS AND DESIGN: We studied 52 adult 46,XY women attending a single-center adult service, who were part of a larger cohort of 400 individuals. Classic conditions such as17ß-hydroxysteroid dehydrogenase deficiency type 3, 5α-reductase deficiency type 2, and androgen insensitivity syndrome were excluded. The study cohort had broad working diagnoses of complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25), a group that included partial gonadal dysgenesis and those with a broad "partial androgen insensitivity syndrome" label. Targeted sequencing of 180 genes was undertaken. RESULTS: Overall, a likely genetic cause was found in 16 of 52 (30.8%) individuals (22.2% CGD, 40.0% pvDSD). Pathogenic variants were found in sex-determining region Y (SRY; n = 3), doublesex and mab-3-related transcription factor 1 (DMRT1; n = 1), NR5A1/steroidogenic factor-1 (SF-1) (n = 1), and desert hedgehog (DHH; n = 1) in the CGD group, and in NR5A1 (n = 5), DHH (n = 1), and DEAH-box helicase 37 (DHX37; n = 4) in the pvDSD group. CONCLUSIONS: Reaching a specific diagnosis can have clinical implications and provides insight into the role of these proteins in sex development. Next-generation sequencing approaches are invaluable, especially in adult populations or where diagnostic biochemistry is not possible.

Dermal suture only versus layered closure: A randomized, split wound comparative effectiveness trial.

BACKGROUND: Layered closure of cutaneous wounds is a commonly used surgical practice. However, there are studies that suggest the additional layer of epidermal sutures might not be necessary. OBJECTIVE: To compare scar outcomes between the single-layer deep-dermal suture technique and the conventional layered suture technique for primary closure of cutaneous wounds. METHODS: A total of 49 patients were enrolled in a prospective, randomized, evaluator-blinded, split scar study to compare the conventional bilayered closure technique with the single-layer deep-dermal suturing technique for primary closure of wounds. The primary outcome measure was mean sum Patient and Observer Scar Assessment Scale (POSAS) score at 3 and 12 months. RESULTS: At the 3-month follow-up, there was a statistically significant difference in the mean total POSAS scores for both the blinded observer and patients, indicating a preference for the side with the standard layered closure. However, at the 12-month follow-up, this difference was lost, with the exception of scar color, which was significantly more noticeable on the wound side closed with only dermal sutures. LIMITATION: Single-center study. CONCLUSION: Three months after surgery, the layered closure technique resulted in a slightly better scar outcome than the single-layered closure containing only dermal sutures. At 12-months' follow-up, this difference diminished, with scars for both sides appearing similar.

Early Home Activities and Oral Language Skills in Middle Childhood: A Quantile Analysis.

Oral language development is a key outcome of elementary school, and it is important to identify factors that predict it most effectively. Commonly researchers use ordinary least squares regression with conclusions restricted to average performance conditional on relevant covariates. Quantile regression offers a more sophisticated alternative. Using data of 17,687 children from the United Kingdom's Millennium Cohort Study, we compared ordinary least squares and quantile models with language development (verbal similarities) at 11 years as the outcome. Gender had more of an effect at the top of the distribution, whereas poverty, early language, and reading to the child had a greater effect at the bottom. The picture for TV watching was more mixed. The results are discussed in terms of the provision of universal and targeted interventions.

Characterization of the microbial community structure and the physicochemical properties of produced water and seawater from the Hibernia oil production platform.

Hibernia is Canada's largest offshore oil platform. Produced water is the major waste byproduct discharged into the ocean. In order to evaluate different potential disposal methods, a comprehensive study was performed to determine the impact from the discharge. Microorganisms are typically the first organisms to respond to changes in their environment. The objectives were to characterize the microbial communities and the chemical composition in the produced water and to characterize changes in the seawater bacterial community around the platform. The results from chemical, physicochemical, and microbial analyses revealed that the discharge did not have a detectable effect on the surrounding seawater. The seawater bacterial community was relatively stable, spatially. Unique microorganisms like Thermoanaerobacter were found in the produced water. Thermoanaerobacter-specific q-PCR and nested-PCR primers were designed, and both methods demonstrated that Thermoanaerobacter was present in seawater up to 1000 m from the platform. These methods could be used to track the dispersion of produced water into the surrounding ocean.

Comparative toxicity of four chemically dispersed and undispersed crude oils to rainbow trout embryos.

The chronic toxicity of crude oil to fish embryos depends on the chemical constituents of the test oil and on factors that control the exposure of embryos to those constituents. The partitioning of chemicals from oil to water depends on the surface area of oil exposed to water and thus on the susceptibility of oil to be dispersed into droplets. The chronic toxicity of four different crude oils to embryos of rainbow trout (Oncorhynchus mykiss) was measured by exposure to the water-accommodated fraction (WAF; no droplet formation) and to the chemically enhanced WAF (CEWAF) of each oil. When effects were compared with the amount of WAF or CEWAF added to test solutions, chemical dispersion increased toxicity dramatically, by >35 to >300-fold, with the smallest difference measured for the lightest and least viscous oil. When effects were compared with measured concentrations of oil in test solutions, there were no differences in toxicity between WAF and CEWAF treatments, indicating that chemical dispersion promoted droplet formation and the partitioning of hydrocarbons from oil to water. On a dilution basis, the differences in toxicity among the four oils were correlated with the concentrations in oil of polynuclear aromatic hydrocarbons (PAH), particularly those with three to five rings, and with their viscosity, an index of dispersibility. However, when PAH concentrations were measured in solution, toxicity did not vary substantially among the four oils, suggesting that the PAH of each oil had equivalent toxicities and that differences in toxicity represented differences in dispersability.

Induction of DNA damage signaling genes in benzidine-treated HepG2 cells.

We examined genotoxicity and DNA damage response in HepG2 cells following exposure to benzidine. Using the Comet assay, we showed that benzidine (50-200 µM) induces DNA damage in HepG2 cells. DNA damage signaling pathway-based PCR arrays were used to investigate expression changes in genes involved in cell-cycle arrest, apoptosis, and DNA repair and showed upregulation of 23 genes and downregulation of one gene in benzidine-treated cells. Induction of G2/M arrest and apoptosis was confirmed at the protein level. Real-time PCR and Western blots were used to demonstrate the expression of select DNA repair-associated genes from the PCR array. Upregulation of the p53 protein in benzidine-treated cells suggests the induction of the p53 DNA damage signaling pathway. Collectively, DNA damage response genes induced by benzidine indicate recruitment complex molecular machinery involved in DNA repair, cell-cycle arrest, and potentially, activation of the apoptosis.

Toxicity of dispersed weathered crude oil to early life stages of Atlantic herring (Clupea harengus).

Reports of the chronic toxicity of dispersed crude oil to early life stages of fish perpetuate uncertainty about dispersant use. However, realistic exposures to dispersed oil in the water column are thought to be much briefer than exposures associated with chronic toxicity testing. To address this issue, the toxicity of dispersed weathered oil to early life stages of Atlantic herring (Clupea harengus) was tested for short exposure durations, ranging from 1 to 144 h. Toxicity was a function of concentration and duration of exposure, as well as of the life stage exposed. Medium South American crude oil dispersed with Corexit 9500 caused blue sac disease in embryos, but not in free-swimming embryos. The age of embryos was negatively correlated with their sensitivity to oil; those freshly fertilized were most sensitive. Sensitivity increased after hatch, with free-swimming embryos showing signs of narcosis. Gametes were also tested; dispersed oil dramatically impaired fertilization success. For exposures of less than 24 h, gametes and free-swimming embryos were the most sensitive life stages. For those of more than 24 h, young embryos (<1 d old) were most sensitive. The results are presented as statistical models that could assist decisions about dispersant use in the vicinity of fish spawning habitats.

Mutation-specific control of BCR-ABL T315I positive leukemia with a recombinant yeast-based therapeutic vaccine in a murine model.

Chromosomal translocations generating the BCR-ABL oncogene cause chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia. The BCR-ABL(T315I) mutation confers drug resistance to FDA-approved targeted therapeutics imatinib mesylate, dasatinib, and nilotinib. We tested the ability of a recombinant yeast-based vaccine expressing the T315I-mutated BCR-ABL antigen to stimulate an anti-BCR-ABL(T315I) immune response. The yeast-based immunotherapy significantly reduced or eliminated BCR-ABL(T315I) leukemia cells from the peripheral blood of immunized animals and extended leukemia-free survival in a murine model of BCR-ABL(+) leukemia compared to animals receiving sham injection or yeast expressing ovalbumin. With immunization, leukemic cells harboring BCR-ABL(T315I) were selectively eliminated after challenge with a mixed population of BCR-ABL and BCR-ABL(T315I) leukemias. In summary, yeast-based immunotherapy represents a novel approach against the emergence of cancer drug resistance by the pre-emptive targeted ablation of tumor escape mutants.

A case of stiff-person syndrome, type 1 diabetes, celiac disease and dermatitis herpetiformis.

Antibodies against glutamic acid decarboxylase (GAD) are involved in the pathophysiology of stiff-person syndrome (SPS) and type 1 diabetes. GAD catalyses the conversion of glutamate to gamma-aminobutyric acid (GABA). GABA acts as a neurotransmitter between neurones, while in pancreatic beta cells it plays an integral role in normal insulin secretion, hence the clinical presentation of muscular spasms in SPS and insulin deficiency in diabetes. Despite this apparent major overlap in pathophysiology, SPS only rarely occurs in individuals with type 1 diabetes. We report the case of a 41-year-old man presenting with a simultaneous diagnosis of both these conditions. His case is unusual in that it is the first reported case in the literature of these conditions occurring in someone with celiac disease (CD) and dermatitis herpetiformis. We discuss why SPS and type 1 diabetes co-exist in only a minority of cases and speculate on the underlying mechanism of the association with CD and dermatitis herpetiformis in our patient.

Central pontine myelinolysis complicating treatment of the hyperglycaemic hyperosmolar state.

Central pontine myelinolysis (CPM) is well recognized to occur in a variety of clinical settings, but particularly following rapid correction of severe hyponatraemia. The development of CPM as a result of rapid shifts in plasma osmolality during the treatment of the hyperglycaemic hyperosmolar state (HHS) has hitherto been described in only one case. We report a second case in which this complication occurred in association with treatment of the HHS. The patient was a 49-year-old woman who presented to another hospital with drowsiness and a plasma glucose of 106 mmol/L. Her admission plasma sodium was 135 mmol/L. She received treatment with intravenous insulin and 0.9% normal saline, and there was a rapid drop in plasma glucose by 60 mmol/L within 6 h, which was associated with a rebound rise of plasma sodium to 159 mmol/L. Her plasma glucose and sodium were later stabilized. When the patient was transferred to our hospital a few days later, she was noted to have flaccid quadraparesis and pseudobulbar palsy. A magnetic resonance imaging scan revealed a pontine lesion consistent with CPM. She made a gradual recovery over several months with intensive rehabilitation and eventually returned to near normal functional capacity. This is the second case report in the literature of CPM complicating the management of HHS and highlights the importance of the judicious and measured correction of hyperglycaemia and the appropriate management of fluid replacement and electrolyte balance when treating this condition.