The impact of xerostomia on oral-health-related quality of life among younger adults

BACKGROUND: Recent research has suggested that chronic dry mouth affects the day-to-day lives of older people living in institutions. The condition has usually been considered to be a feature of old age, but recent work by our team produced the somewhat surprising finding that 10% of people in their early thirties are affected. This raises the issue of whether dry mouth is a trivial condition or a more substantial threat to quality of life among younger people. The objective of this study was to examine the association between xerostomia and oral-health-related quality of life among young adults while controlling for clinical oral health status and other potential confounding factors. METHODS: Cross-sectional analysis of data from a longstanding prospective observational study of a Dunedin (New Zealand) birth cohort: clinical dental examinations and questionnaires were used at age 32. The main measures were xerostomia (the subjective feeling of dry mouth, measured with a single question) and oral-health-related quality of life (OHRQoL) measured using the short-form Oral Health Impact Profile (OHIP-14). RESULTS: Of the 923 participants (48.9% female), one in ten were categorised as 'xerostomic', with no apparent gender difference. There was a strong association between xerostomia and OHRQoL (across all OHIP-14 domains) which persisted after multivariate analysis to control for clinical characteristics, gender, smoking status and personality characteristics (negative emotionality and positive emotionality). CONCLUSION: Xerostomia is not a trivial condition; it appears to have marked and consistent effects on sufferers' day-to-day lives

A study of acromegaly-associated headache with somatostatin analgesia.

To characterise somatostatin analogue responsive headache in acromegaly, hitherto not systematically documented in a significant cohort. Using the UK pituitary network, we have clinically characterised a cohort of 18 patients suffering from acromegaly-related headache with a clear response to somatostatin analogues. The majority of patients had chronic migraine (78%) as defined by the International Headache Society diagnostic criteria. Headache was present at the time of acromegaly presentation and clearly associated temporally with disease activity in all cases. Short-acting somatostatin analogues uniquely resolved pain within minutes and the mean duration of analgesia was 1-6 hours. Patients on long-acting analogues required less short-acting injections (mean 3.7 vs. 10.4 injections per day, p=0.005). 94% used somatostatin analogues to control ongoing headache pain. All patients presented with macroadenoma, most had incomplete resection (94%) and headache was ipsilateral to remnant tissue (94%). Although biochemical control was achieved in 78% of patients, headache remained in 71% of them. Patients selected for this study had ongoing headache post-treatment (mean duration 16 years after diagnosis); only 4 patients reached headache remission 26 years (mean, range 14-33) after the diagnosis. Headache in acromegaly patients can be persistent, severe, unrelieved by surgery, long-lasting and uncoupled from biochemical control. We show here that long-acting analogues allow a decrease in the number of short-acting analogue injections for headache relief. Further studies are needed to understand the mechanisms, markers and tumour tissue characteristics of acromegaly-related headache. Until then, this publication serves to provide the clinical characteristics as a reference point for further study

Smc5/6: a link between DNA repair and unidirectional replication?

Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity

Join forces or cheat: evolutionary analysis of a consumer-resource system

International audienceIn this contribution we consider a seasonal consumer-resource system and focus on the evolution of consumer behavior. It is assumed that consumer and resource individuals live and interact during seasons of fixed lengths separated by winter periods. All individuals die at the end of the season and the size of the next generation is determined by the the consumer-resource interaction which took place during the season. Resource individuals are assumed to reproduce at a constant rate, while consumers have to trade-off between foraging for resources, which increases their reproductive abilities, or reproducing. Firstly, we assume that consumers cooperate in such a way that they maximize each consumer's individual fitness. Secondly, we consider the case where such a population is challenged by selfish mutants who do not cooperate. Finally we study the system dynamics over many seasons and show that mutants eventually replace the original cooperating population, but are finally as vulnerable as the initial cooperating consumers

Opportunities for improving pLDH-based malaria diagnostic tests

<p>Abstract</p> <p>Background</p> <p>Monoclonal antibodies to <it>Plasmodium </it>lactate dehydrogenase (pLDH) have been previously used to format immunochromatographic tests for the diagnosis of malaria. Using pLDH as an antigen has several advantages as a sensitive measure of the presence of parasites within patient blood samples. However, variable results in terms of specificity and sensitivity among different commercially available diagnostic kits have been reported and it has not been clear from these studies whether the performance of an individual test is due simply to how it is engineered or whether it is due to the biochemical nature of the pLDH-antibody reaction itself.</p> <p>Methods</p> <p>A series of systematic studies to determine how various pLDH monoclonal antibodies work in combination was undertaken. Different combinations of anti-pLDH monoclonal antibodies were used in a rapid-test immunochromatographic assay format to determine parameters of sensitivity and specificity with regard to individual <it>Plasmodium </it>species.</p> <p>Results</p> <p>Dramatic differences were found in both species specificity and overall sensitivity depending on which antibody is used on the immunochromatographic strip and which is used on the colorimetric colloidal-gold used for visual detection.</p> <p>Discussion</p> <p>The results demonstrate the feasibility of different test formats for the detection and speciation of malarial infections. In addition, the data will enable the development of a universal rapid test algorithm that may potentially provide a cost-effective strategy to diagnose and manage patients in a wide range of clinical settings.</p> <p>Conclusion</p> <p>These data emphasize that using different anti-pLDH antibody combinations offers a tractable way to optimize immunochromatographic pLDH tests.</p

Cytochrome P450 CYP1B1 activity in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n = 11). Measurable levels of active P450R were determined in all normal (n = 11) and tumour samples (n = 26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers