Evaluating skeletal indices to study maturation: past vs. present

OBJECTIVE: To compare skeletal maturation of female and male subjects from historic samples to present day subjects by assessing Fishman’s Skeletal Maturity Index (SMI). Present day eating habits and lifestyle have been suggested as factors in accelerating pubertal maturation seen within the last century. Consequently, Body Mass Index (BMI) as well as BMI percentile were evaluated to determine whether it is associated with significant differences in skeletal maturation patterns. METHODS: This pilot study included hand-wrist films from 92 subjects from the Burlington and Forsyth longitudinal growth studies (1959-1970) and 146 patients currently enrolled in the Orthodontic department of the Boston University Henry M. Goldman School of Dental Medicine (BUGSDM). The age of the subjects ranged between 7 and 16 years. SMI stage was determined and BMI and BMI percentile were calculated for each subject. RESULTS: The mean chronologic ages of all the SMI stages were not different in males or females when comparing the historic sample to the present sample except for the mean ages at SMI stage 7 and 11 for females and SMI stage 5 for males. Females in the present sample reached SMI stages 7 and 11 significantly earlier: 11.6 versus 13.3 years for SMI 7 (p<0.001) and 15.6 vs. 16.0 for SMI 11 (p<0.05). Males in the present sample also reached SMI 5 significantly earlier: 12.5 vs 13.8 years (p<0.05). It was also seen that present day females at SMI stage 11 not only matured earlier, but also had significantly higher mean BMI and mean BMI percentile than the females at the same stage in the historic sample. This suggests that BMI may be associated with acceleration of maturation among females at SMI stage 11 (p<0.05). CONCLUSIONS: In both male and female subjects, there are differences between past and present populations at certain SMI stages. This evidence suggests that patterns of skeletal maturation may have changed and BMI may be associated with such changes. The differences in skeletal maturation between the two groups may also be a result of the different distribution of race in each group. In the current study, the historic sample consists of only Caucasian subjects whereas the present sample consists of subjects from many different backgrounds. As a result, effects of racial variations could have additionally played a role in the changes seen in skeletal maturation patterns. Increasing our sample size and controlling for race may help further elucidate these changes and determine if this transition towards earlier maturation is in fact due to increasing BMIs

Dental Care Utilization and Satisfaction of Residential University Students

Aim: The objective of this study was to provide information on the level of utilization and satisfaction of residential university students with the dental services provided by the dental clinic of a teaching hospital. Volunteers and Material: A stratified sampling technique was used to recruit volunteers from the outpatient clinic of the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria. Information was collected by a self-administered questionnaire composed of questions that measure the level of utilization and satisfaction with the dental services provided. Questionnaires were provided to 650 randomly chosen students residing in the University hostels. There were 39 refusals, and 6 incomplete questionnaires were discarded. This left a sample size of 605 volunteers. Results: Forty seven students (7.8%) indicated that they visited the dental hospital within the last 12 months. Males and females utilized the dental services equally, and utilization increased with age and the number of years spent on campus. Anticipation of painful dental treatment, high dental charges, long waiting times and being too busy for a dental visit were cited as the most important impediments to seeking dental treatment. Females expressed greater satisfaction with the services. Conclusion: Dental service utilization among the students was found to be low. Oral health awareness campaigns, improving the quality of the services, and shortening the waiting time are expected to increase service utilization and satisfaction. Keywords: dental care, utilization, satisfaction, young adults, Nigeria Libyan Journal of Medicine Vol. 3 (3) 2008: pp. 20-2

Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study

Background: Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with Cystic Fibrosis

There are controversies about the most effective treatment to eradicate first growth of Pseudomonas aeruginosa (P aeruginosa) from the lower airways of patients with cystic fibrosis (CF). UK guidelines recommend oral treatment, but some advocate intravenous (IV) treatment. The objective of this study was to assess the feasibility of conducting a randomised controlled trial comparing two treatment strategies to eradicate P aeruginosa in CF patients

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

A feasibility study exploring the role of pre-operative assessment when examining the mechanism of ‘chemo-brain’ in breast cancer patients

Background: Women receiving chemotherapy treatment for breast cancer may experience problems with their memory and attention (cognition), which is distressing and interferes with quality of life. It is unclear what causes or contributes to the problems they report: psychological distress, fatigue, coping style, or specific biological changes for example to pro inflammatory cytokines. Research shows however, that approximately a third of women with breast cancer perform poorly on tests of cognition before commencing chemotherapy. We aimed to examine the acceptability and relevance of pre-surgical assessments (bloods, brain imaging, cognitive tests and self-report questionnaires) when investigating the phenomenon of ‘chemo-brain’ and investigate whether inflammatory markers mediate chemotherapy-induced neuropsychological impairments in women treated for breast cancer. Methods: Women with early stage breast cancer completed neuropsychological and quality of life assessments at T1 (pre-surgery), T2 (post-surgery before chemotherapy) and T3 (6 months later). Blood cytokine levels were measured at the same time points and brain imaging was performed at T1 and T3. Results: In total, 14/58 women participated (8 chemotherapy, 6 non-chemotherapy). Prior to the start of chemotherapy a decline in cognitive performance compared to baseline was observed in one participant. At T3 women who received chemotherapy reported poorer quality of life and greater fatigue. Increases in soluble tumour necrosis factor receptor II (sTNFRII), interleukin-6, interleukin-10 and vascular endothelial growth factor occurred post chemotherapy only. Levels of sTNFRII were inversely correlated with grey matter volume (GMV) of the right posterior insula in both groups. At T3, the chemotherapy group displayed a greater reduction in GMV in the subgenual and dorsal anterior cingulate, and the inferior temporal gyrus. Conclusions: Pre-operative recruitment to the study was challenging; however, the lack of significant changes in blood cytokine levels and neuropsychological tests at T2 implies that post surgery may be a valid baseline assessment, but this needs further investigation in a larger study. The preliminary results support the hypothesis that chemotherapy induced fatigue is mediated by a change in peripheral cytokine levels which could explain some symptoms of ‘chemo brain’ experienced by patients

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K

Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity. Although TMEM16K is widely distributed and associated with the neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location in cells, function and structure are largely uncharacterised. Here we show that TMEM16K is an ER-resident lipid scramblase with a requirement for short chain lipids and calcium for robust activity. Crystal structures of TMEM16K show a scramblase fold, with an open lipid transporting groove. Additional cryo-EM structures reveal extensive conformational changes from the cytoplasmic to the ER side of the membrane, giving a state with a closed lipid permeation pathway. Molecular dynamics simulations showed that the open-groove conformation is necessary for scramblase activity

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Caring for Caregivers (C4C): study protocol for a pilot feasibility randomised control trial of Positive Written Disclosure for older adult caregivers of people with psychosis

Background: The caregivers of people who experience psychosis are themselves at risk of developing physical and mental health problems. This risk is increased for older adult caregivers who also have to manage the lifestyle and health changes associated with ageing. As a consequence, older adult caregivers are in particular need of support; we propose a Written Emotional Disclosure (WED) intervention, called Positive Written Disclosure (PWD). Methods/design: This is a pilot randomised controlled trial of PWD compared to a neutral writing control and a no writing condition. We aim to recruit 60 participants, 20 in each arm. This study will utilise a mixed-methods approach and collect quantitative (questionnaires) and qualitative (interviews) data. Quantitative data will be collected at baseline and 1, 3, and 6 months post baseline. Participants who complete a writing task (PWD or neutral writing control) will be invited to complete an exit interview to discuss their experiences of the intervention and study. The study is supported by a patient and public involvement group. Discussion: The results of this trial will determine whether a definitive trial is justified. If so, the quantitative and qualitative findings will be used to refine the intervention and study protocols