Awareness of social care needs in people with epilepsy and intellectual disability.

BACKGROUND: Nearly a quarter of people with intellectual disability (ID) have epilepsy with large numbers experiencing drug-resistant epilepsy, and premature mortality. To mitigate epilepsy risks the environment and social care needs, particularly in professional care settings, need to be met. PURPOSE: To compare professional care groups as regards their subjective confidence and perceived responsibility when managing the need of people with ID and epilepsy. METHOD: A multi-agency expert panel developed a questionnaire with embedded case vignettes with quantitative and qualitative elements to understand training and confidence in the health and social determinants of people with ID and epilepsy. The cross-sectional survey was disseminated amongst health and social care professionals working with people with ID in the UK using an exponential non-discriminative snow-balling methodology. Group comparisons were undertaken using suitable statistical tests including Fisher's exact, Kruskal-Wallis, and Mann-Whitney. Bonferroni correction was applied to significant (p < 0.05) results. Content analysis was conducted and relevant categories and themes were identified. RESULTS: Social and health professionals (n = 54) rated their confidence to manage the needs of people with ID and epilepsy equally. Health professionals showed better awareness (p < 0.001) of the findings/recommendations of the latest evidence on premature deaths and identifying and managing epilepsy-related risks, including the relevance of nocturnal monitoring. The content analysis highlighted the need for clearer roles, improved care pathways, better epilepsy-specific knowledge, increased resources, and better multi-disciplinary work. CONCLUSIONS: A gap exists between health and social care professionals in awareness of epilepsy needs for people with ID, requiring essential training and national pathways.

DNA repair and response to sperm DNA damage in oocytes and embryos, and the potential consequences in ART: a systematic review.

Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos have adopted specific response and repair mechanisms to repair DNA damage of paternal origin. We have conducted a systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify and review the maternal mechanisms used to respond and repair sperm DNA damage during early embryonic development, how these mechanisms operate and their potential clinical implications. The literature search was conducted in Ovid MEDLINE and Embase databases until May 2021. Out of 6297 articles initially identified, 36 studies were found to be relevant through cross referencing and were fully extracted. The collective evidence in human and animal models indicate that the early embryo has the capacity to repair DNA damage within sperm by activating maternally driven mechanisms throughout embryonic development. However, this capacity is limited and likely declines with age. The link between age and decreased DNA repair capacity could explain decreased oocyte quality in older women, poor reproductive outcomes in idiopathic cases and patients who present high sperm DNA damage. Ultimately, further understanding mechanisms underlying the maternal repair of sperm DNA damage could lead to the development of targeted therapies to decrease sperm DNA damage, improved oocyte quality to combat incoming DNA insults or lead to development of methodologies to identify individual spermatozoa without DNA damage.

Dealer's Dytonia (Croupier's Cramp) - An Unusual Hazard Of Gambling.

Dystonia takes many forms and often presents acutely to emergency care. The diagnosis is often delayed because it mimics other more common conditions. This report describes a patient with a rare occupational dystonia, the typical clinical features of dystonia in general, and differentials to consider.

Male patients affected by mosaic PCDH19 mutations: five new cases.

Pathogenic variants in the PCDH19 gene are associated with epilepsy, intellectual disability (ID) and behavioural disturbances. Only heterozygous females and mosaic males are affected, likely due to a disease mechanism named cellular interference. Until now, only four affected mosaic male patients have been described in literature. Here, we report five additional male patients, of which four are older than the oldest patient reported so far. All reported patients were selected for genetic testing because of developmental delay and/or epilepsy. Custom-targeted next generation sequencing gene panels for epilepsy genes were used. Clinical data were collected from medical records. All patients were mosaic in blood for likely pathogenic variants in the PCDH19 gene. In most, clinical features were very similar to the female phenotype, with normal development before seizure onset, which occurred between 5 and 10 months of age, clustering of seizures and sensitivity to fever. Four out of five patients had mild to severe ID and behavioural problems. We reaffirm the similarity between male and female PCDH19-related phenotypes, now also in a later phase of the disorder (ages 10-14 years).

Cardiovascular risk reduction in hypertension: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers. Where are we up to?

Previously, management of hypertension has concentrated on lowering elevated blood pressure. However, the target has shifted to reducing absolute cardiovascular (CV) risk. It is estimated that two in three Australian adults have three or more CV risk factors at the same time. Moderate reductions in several risk factors can, therefore, be more effective than major reductions in one. When managing hypertension, therapy should be focused on medications with the strongest evidence for CV event reduction, substituting alternatives only when a primary choice is not appropriate. Hypertension management guidelines categorise angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) interchangeably as first-line treatments in uncomplicated hypertension. These medications have different mechanisms of action and quite different evidence bases. They are not interchangeable and their prescription should be based on clinical evidence. Despite this, currently ARB prescriptions are increasing at a higher rate than those for ACEI and other antihypertensive classes. Evidence that ACEI therapy prevents CV events and death, in patients with coronary artery disease or multiple CV risk factors, emerged from the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) trials respectively. The consistent benefit has been demonstrated in meta-analyses. The clinical trial data for ARB are less consistent, particularly regarding CV outcomes and mortality benefit. The evidence supports the use of ACEI (Class 1a) compared with ARB despite current prescribing trends.

Transoral robotic surgery alone for oropharyngeal cancer: an analysis of local control.

OBJECTIVE: To evaluate local control following transoral robotic surgery (TORS) with the da Vinci Surgical System (Intuitive Surgical Inc) as a single treatment modality for oropharyngeal squamous cell carcinoma (OSCC). DESIGN: Prospective, single-center, observational study. SETTING: Academic university health system and tertiary referral center. PATIENTS: Thirty adults with previously untreated OSCC. INTERVENTION: Transoral robotic surgery with staged neck dissection as indicated. MAIN OUTCOME MEASURES: Local control and margin status. RESULTS: Thirty patients were enrolled with previously untreated OSCC and no prior head and neck radiation therapy. Follow-up duration was at least 18 months. At the time of diagnosis, 9 tumors were T1 (30%); 16 were T2 (53%); 4 were T3 (13%); and 1 was T4a (3%). The anatomic sites of these primary tumors were tonsil in 14 (47%), tongue base in 9 (30%), glossotonsillar sulcus in 3 (10%), soft palate in 3 (10%), and oropharyngeal wall in 1 (3%). There was only 1 patient (3%) who had a positive margin after primary resection; further resection achieved a final negative margin. Perineural invasion was noted in 3 tumors (10%). No patient received postoperative adjuvant therapy. At a mean follow-up of 2.7 years (range, 1.5-5.1 years), there was 1 patient with local failure (3%). CONCLUSION: As the only modality used for treatment of pathologically low-risk OSCCs, TORS provides high local control and is associated with low surgical morbidity.

Periodontitis is associated with altered plasma fatty acids and cardiovascular risk markers.

BACKGROUND AND AIMS: In periodontitis it has been found that some perturbation exists in lipid biomarkers, such as increased serum total cholesterol and low-density lipoprotein cholesterol. Nevertheless, the relationship between fatty acids and periodontitis has been demonstrated only in a few studies and remains controversial. The aim of this investigation was to explore the effects of periodontitis on a cluster of traditional and novel cardiovascular risk factors such as plasma-lipids profile, types of plasma fatty acids, adhesion molecules and systemic inflammatory markers. METHODS AND RESULTS: At a university dental school, 56 patients all over 35 years old were enrolled and invited to participate in the study. Total plasma fatty acids, saturated, n-6 polyunsaturated and monounsaturated fatty acids, peroxidability index, soluble VCAM, TNF-alpha, cholesterol, triacylglycerols, and VLDL-c were significantly higher in the periodontitis group compared to the non-periodontitis group. CONCLUSIONS: This close association found between plasma triacylglycerols, LDL-c, saturated fatty acids, polyunsaturated fatty acids, total amount of fatty acids and coenzyme Q(10) with some periodontal data such as periodontal probing depth, recession of the gingival margin and clinical attachment level (Pearson correlation between 0.3 and 0.6), leads to the conclusion that there is an inter-relationship between periodontitis, plasma fatty acids profile and the increase in metabolic risk factors for cardiovascular diseases.

Metabolic syndrome and periodontitis: is oxidative stress a common link?

A review of pathological mechanisms that can explain the relationship between periodontitis and cardiovascular disease (CVD) is necessary to improve the management of both conditions. Metabolic syndrome is a combination of obesity, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia, and dyslipidemia. All these have been examined in recent years in terms of their relationship to periodontitis. Reviewed data indicate an association between some of them (body mass index, high-density lipoprotein-cholesterol [HDL-C], triglycerides, high blood pressure, among others) and periodontitis. Oxidative stress may act as a potential common link to explain relationships between each component of metabolic syndrome and periodontitis. Both conditions show increased serum levels of products derived from oxidative damage, with a pro-inflammatory state likely influencing each other bidirectionally. Adipocytokines might modulate the oxidant/anti-oxidant balance in this relationship.

Nifedipine and cyclosporin affect fibroblast calcium and gingiva.

It has been stated that cyclosporin and nifedipine produce gingival overgrowth. However, the specific pathogenic mechanism remains uncertain. We used an experimental rat model to test the hypothesis that changes in collagen metabolism and numbers of gingival blood vessels are not mediated by intracellular calcium concentration (ratiometric Fura-2 AM measurement) in gingival fibroblasts. In the cyclosporin group, both width (364.2 +/- 67.5 mum) and microvessel density (number of vessels/mm(2), stained with anti-CD34 antibody) (41.6 +/- 5.1) of gingiva were statistically different when compared with those in the control group (width = 184.3 +/- 35.2 mum, microvessel density = 19.6 +/- 2.4). The nifedipine group showed the highest content of collagen (proportion of total stroma occupied by collagen, stained with Picro-Mallory) (nifedipine group = 66.3 +/- 9.4, cyclosporin group = 55.2 +/- 7.9, control group = 30.1 +/- 10.2). Freshly cultured fibroblasts from the cyclosporin group exhibited higher ratiometric values of fluorescence than did both the control and nifedipine groups (p = 0.03). Our results support the hypothesis that changes in gingival collagen metabolism are not mediated by calcium intracellular oscillations.

The effects of a supervised toothbrushing programme on the caries increment of primary school children, initially aged 5-6 years.

Children in the London Boroughs of Kensington, Chelsea and Westminster have one of the highest levels of caries in England and Wales. In 1997/98, the mean dmft for 5-year-old children was 2.83 with only 45.9% of the children being caries free. The aim of this study was to determine whether teacher-supervised toothbrushing, once a day, at school, during term time, with commercial toothpaste containing 1,450 ppm fluoride, could reduce dental caries in primary school children when compared with children from the same community who did not receive this intervention. A total of 517 children (mean age 5.63 years) were recruited for the study. Class teachers were trained individually by the same dental hygienist in an appropriate toothbrushing technique for young children. Children in the intervention group brushed once a day at school. All examinations were by visual assessment only. All teeth present were assessed using the BASCD criteria. For children in the intervention group, the overall caries increment (2.60) was significantly less (10.9%; p < 0.001) than for children in the non-intervention group (2.92). Among different tooth surfaces, the difference in caries increment between the intervention group (0.78) and the non-intervention group (1.03) was greatest for the proximal surfaces (21.4%; p < 0.01). In conclusion, this study suggests that a programme of daily teacher-supervised toothbrushing with fluoride toothpaste can be effectively targeted into socially deprived communities and a significant reduction in dental caries can thereby be achieved especially among caries-susceptible children.

Sustained oral health improvement and use of toothbrushes and dentifrice by previous users of traditional materials in a rural population in Andhra Pradesh, India.

AIM: To follow-up, one year later, a double-blind, randomised study, which investigated the effect of regular brushing with dentifrices on the oral health of an economically disadvantaged rural population in Andhra Pradesh, India who were primarily users of traditional materials. SUBJECTS: 150 of the original study population. METHOD: Examination to determine whether the improvements in oral health status and oral health behaviour (use of toothbrush and dentifrice), being unsupported, had been sustained since completion of the original study. RESULTS: Data analysis showed sustained, statistically significant improvements in gingival health as measured by gingival bleeding and plaque indices (GBI and PI) comparing users and non-users of toothbrushes and dentifrice in the original study (PI: p = 0.04; GBI: p = 0.03) and sustained use of toothbrushes and dentifrice by 60% of the subjects at follow-up one year later. CONCLUSIONS: This study shows a beneficial effect on oral hygiene indices following the introduction of toothbrushes and dentifrices to a community using traditional oral hygiene materials and sustainability of use of these materials with motivation and support. It may therefore be concluded that it is feasible to achieve significant use of conventional toothbrushes and toothpastes, with consequent major and sustained improvements in plaque control and gingival health in a disadvantaged population hitherto often considered as not amenable to conventional oral hygiene for cultural or economic reasons.

Clinical evaluation of ferric oxalate in relieving dentine hypersensitivity.

Previous in vitro permeability and scanning electron microscopic (SEM) studies have demonstrated the effectiveness of the oxalate ion in dentine permeability reduction and effective tubule occlusion. The aim of this randomized double-blind, split mouth 4-week clinical study, therefore was to determine whether a 1-min application of ferric oxalate (Sensodyne Sealant) on exposed root dentine was effective in reducing dentine hypersensitivity (DH). Thirteen subjects [8F:5M, mean age 46.2 (s.d. 4.15) years] completed the study. The subjective response was evaluated by tactile, thermal and evaporative methods of assessment. Data were collected at baseline and post-application at +5 min and 4 weeks. Analysis was based on paired t-test (P=0.05) and Wilcoxon-Mann-Whitney tests. No statistically significant differences were noted between ferric oxalate and placebo preparations at +5 min and 4 weeks for any of the test stimuli. There was, however, a clear trend towards immediate reduction (+5 min) in DH reverting back to baseline values at 4 weeks with the exception of the Biomat Thermal Probe mean values, which maintained the reductions in DH compared with placebo. The results of the present study demonstrated that a 1-min application of ferric oxalate is both rapid and effective in reducing DH although its long-term effectiveness still needs to be determined.

A survey of dental hygienist numbers in Canada, the European Economic area, Japan and the United States of America in 1998.

OBJECTIVE: The aims of this study were to establish how many dental hygienists were licensed to practice in Canada, Japan, USA and the 18 member states of the European Economic Area (EEA) and to compare these with the populations and numbers of dentists practising in the countries concerned. METHOD: Data for the overall populations, numbers of 'active' dentists, of dental hygienists and of employed dental hygienists in the member states of the EEA in 1998 were taken from the responses to a Council of European Chief Dental Officers survey carried out in 2000/2001. Data for these variables for Canada, Japan and the USA in 1998 were accessed from published reports. The ratios of population: active dentist; population: dental hygienist; and active dentist: dental hygienist were calculated and compared. RESULTS: The overall populations and total number of active dentists in the 18 EEA member states and Canada plus Japan plus the USA were broadly similar in 1998 (EEA overall population 381 million with 245169 active dentists: Canada/Japan/USA overall population 421 million with 253825 active dentists). However, there were only 13295 dental hygienists in the EEA as opposed to a total of 215435 in Canada, Japan and the USA. In terms of population:dental hygienist and active dentist: dental hygienist ratios the UK was found to have proportionally far fewer dental hygienists than Canada, Japan, USA or the four Nordic members of the EEA. CONCLUSION: The survey revealed that relative to overall populations and numbers of dentists, there are far fewer dental hygienists in the EEA than in Canada, Japan and the USA and that scope for the UK to import dental hygienists from other EEA member states is probably very limited.

Keratinocyte growth factor receptor is up-regulated in cyclosporin A-induced gingival hyperplasia.

Keratinocyte growth factor stimulates the growth and activity of epithelial cells via the keratinocyte growth factor receptor. We have recently shown that the growth factor is markedly elevated in cyclosporin A-induced gingival hyperplasia tissue in vivo, but the effects of cyclosporin A on the receptor are not yet known. The present study was therefore carried out to determine whether expression of the keratinocyte growth factor receptor is up-regulated in gingival hyperplasia compared with normal gingiva. Using immunohistochemistry and the reverse-transcribed polymerase chain-reaction, we obtained results which showed that receptor antigen and gene transcript levels were both elevated in gingival hyperplasia tissue. In addition, flow cytometry and the reverse-transcribed polymerase chain-reaction showed that the receptor and mRNA were also higher in gingival epithelial cells following incubation with cyclosporin A in vitro. These findings suggest that the keratinocyte growth factor-receptor pathway of mesenchymal-epithelial interaction could play an important part in the molecular pathogenesis of gingival hyperplasia.

Non-targeted effects of radiation: bystander responses in cell and tissue models.

The standard paradigm for radiation effects in cellular systems has involved direct damage to DNA and in particular, DNA double strand breaks as the triggering lesions leading to mutation, cell death and transformation. Recently, however, a growing body of evidence has reported non-targeted effects, which are not a direct consequence of the initial lesions produced in cellular DNA. These have included bystander responses, genomic instability, gene induction, adaptive responses and low dose hypersensitivity. A common observation of these responses is that they dominate at low doses and saturate with increasing dose. Non-targeted effects may therefore have consequences for extrapolation of risk estimates to low doses if these are important in vivo. A range of experimental techniques is being used to study non-targeted responses, including microbeam approaches. Microbeams have considerable advantages in that they allow individual cells and subcellular targets to be selected within populations with precise low doses and, if required, exact dose rates. Recent advances also allow targeting of 3-D cell systems. The mechanisms underlying non-targeted responses appear to involve production of reactive oxygen species and direct cell-to-cell signalling via gap junctional intercellular communication although significant differences exist in different cell types. The triggering lesions for these responses remain unclear however. Some non-targeted responses may be inter-related, for example in the case of bystander responses and instability and may be part of a general stress response system in irradiated populations. Some non-targeted effects may also act as protective mechanisms; if they lead to the removal of potentially damaged cells from the population.

Development of an in vitro microassay for glucose quantification in submicrolitre volumes of biological fluid.

Glucose quantification in serum or plasma is traditionally based on a colourimetric enzymatic assay using commercially available assay kits. Sample volumes of blood or serum are usually in the range of a few microlitres to a few millilitres. However, for biological fluids such as gingival crevicular fluid (GCF), which can only be sampled in submicrolitre volumes, such assays have proven unsuitable. The aim of this study was to develop a reliable and reproducible assay for quantifying glucose in submicrolitre samples of GCF. The assay involved modification of a commercially available kit for glucose quantification. Test solutions of (i) serum and (ii) serum with added glucose at known concentrations (range 50-400 mg/dl) were prepared to simulate GCF and GCF enriched with glucose, respectively. Submicrolitre volumes (range 0.2 microl to 0.8 microl) of the test solutions were added to the reagent solution (200 microl) using a Hamilton syringe. The reaction was performed under standard conditions of time and temperature. The colour change was assayed spectrophotometrically at 492 nm. The results showed that this microassay is sufficiently sensitive to detect 50 mg/dl glucose in 0.2 microl of sample and indicate that the accuracy and sensitivity of this assay make it suitable for glucose quantification in submicrolitre volumes of GCF, particularly relevant to investigations of the relationship between diabetes mellitus and chronic inflammatory periodontal disease. In vivo evaluation of this novel microassay was performed using GCF samples taken from periodontally healthy and chronic periodontitis patients. Using non-parametric analysis, the results showed that the assay detected statistically significant differences in glucose concentrations between the two patient groups (p < 0.05). Higher glucose levels were detected at the periodontally diseased sites. For each patient, the GCF-glucose: blood-glucose ratio was calculated. The results show that this ratio was higher in the periodontitis group (1: 2) when compared to the healthy group (1: 9). In conclusion, the results of this investigation have shown that this microassay can quantify glucose in GCF and that GCF-glucose levels are higher at periodontitis sites.