Assessing oral health-related quality of life in general dental practice in Scotland: validation of the OHIP-14

OBJECTIVES: To validate the Oral Health Impact Profile (OHIP)-14 in a sample of patients attending general dental practice. METHODS: Patients with pathology-free impacted wisdom teeth were recruited from six general dental practices in Tayside, Scotland, and followed for a year to assess the development of problems related to impaction. The OHIP-14 was completed at baseline and at 1-year follow-up, and analysed using three different scoring methods: a summary score, a weighted and standardized score and the total number of problems reported. Instrument reliability was measured by assessing internal consistency and test-retest reliability. Construct validity was assessed using a number of variables. Linear regression was then used to model the relationship between OHIP-14 and all significantly correlated variables. Responsiveness was measured using the standardized response mean (SRM). Adjusted R(2)s and SRMs were calculated for each of the three scoring methods. Estimates for the differences between adjusted R(2)s and the differences between SRMs were obtained with 95% confidence intervals. RESULTS: A total of 278 and 169 patients completed the questionnaire at baseline and follow-up, respectively. Reliability - Cronbach's alpha coefficients ranged from 0.30 to 0.75. Alpha coefficients for all 14 items were 0.88 and 0.87 for baseline and follow-up, respectively. Test-retest coefficients ranged from 0.72 to 0.78. Validity - OHIP-14 scores were significantly correlated with number of teeth, education, main activity, the use of mouthwash, frequency of seeing a dentist, the reason for the last dental appointment, smoking, alcohol intake, pain and symptoms. Adjusted R(2)s ranged from 0.123 to 0.202 and there were no statistically significant differences between those for the three different scoring methods. Responsiveness - The SRMs ranged from 0.37 to 0.56 and there was a statistically significant difference between the summary scores method and the total number of problems method for symptomatic patients. CONCLUSIONS: The OHIP-14 is a valid and reliable measure of oral health-related quality of life in general dental practice and is responsive to third molar clinical change. The summary score method demonstrated performance as good as, or better than, the other methods studied.     

SNPSplicer: systematic analysis of SNP-dependent splicing in genotyped cDNAs

Functional annotation of SNPs (as generated by HapMap (http://www.hapmap.org) for instance) is a major challenge. SNPs that lead to single amino acid substitutions, stop codons, or frameshift mutations can be readily interpreted, but these represent only a fraction of known SNPs. Many SNPs are located in sequences of splicing relevance-the canonical splice site consensus sequences, exonic and intronic splice enhancers or silencers (exonic splice enhancer [ESE], intronic splice enhancer [ISE], exonic splicing silencer [ESS], and intronic splicing silencer [ISS]), and others. We propose using sets of matching DNA and complementary DNA (cDNA) as a screening method to investigate the potential splice effects of SNPs in RT-PCR experiments with tissue material from genotyped sources. We have developed a software solution (SNPSplicer; http://www.ikmb.uni-kiel.de/snpsplicer) that aids in the rapid interpretation of such screening experiments. The utility of the approach is illustrated for SNPs affecting the donor splice sites (rs2076530:A>G, rs3816989:G>A) leading to the use of a cryptic splice site and exon skipping, respectively, and an exonic splice enhancer SNP (rs2274987:C/T), leading to inclusion of a new exon. We anticipate that this methodology may help in the functional annotation of SNPs in a more high-throughput fashion.     

Short-term nitrogen dioxide exposure and geomagnetic activity interaction: contribution to emergency hospitalization for acute coronary syndrome

We investigated whether extremely geomagnetic activity may modify the association between short-term nitrogen dioxide (NO₂) exposure and emergency hospitalization for acute coronary syndrome (ACS). A case-crossover study design was used to analyze ACS in 6,594 hospitalized patients at the Clinic of Kaunas, Lithuania. We evaluated the associations between NO₂, geomagnetic activity and the rate of emergency admissions for ACS by logistic regression controlling for seasonal variation, weekdays and meteorological factors. Ambient NO₂ pollution interquartile range increase (IQR) on the day of admission and previous day (lag 0–1) in patients below 65 years of age increase the risk of ACS equal to 24% (95% CI 0.96–1.60). Evidence of effect modification by combined NO₂ and geomagnetic activity was observed in relation to ACS, adjusted OR was 1.61; 95% CI 1.03–2.53. In conclusion, these findings suggest that geomagnetic activity variations may increase the traffic-related air pollution effect on ACS, and highlight environmental factors associated with ischemic heart disease course.     

The effect of Ginkgo biloba extract on mitochondrial oxidative phosphorylation in the normal and ischemic rat heart

Free radical‐induced myocardial damage and impairment of vascular endothelium‐dependent relaxation are amongst the most important mechanisms responsible for ischemic heart injury. Ginkgo biloba leaf extract (GE) has been reported to improve blood circulation in the brain and have a beneficial impact on the cardiovascular system but its cardioprotective effects have not been elucidated yet. Therefore, this study investigated the influence of GE in 70% ethanol (1:5) administered orally to rats on the functions of isolated heart mitochondria under normal and ischemic conditions. Wistar rats were given GE or ethanol (solvent control) at a dosage of 0.32 mL/kg in drinking water for 10 and 18 days, while the control animals received untreated drinking water. Mitochondrial respiration rates were determined oxygraphically. Pyruvate and malate, succinate or palmitoyl‐l ‐carnitine and malate were used as substrates. The GE treatment partially uncoupled mitochondrial oxidation from phosphorylation, reduced the generation of free radicals in the mitochondria, diminished the ischemia‐induced V₃ decrease and the degree of respiration stimulation by exogenous cytochrome c. Thus, these results indicate that GE exerts cardioprotective effects reducing ischemia‐caused impairment of the functions of heart mitochondria. Copyright © 2011 John Wiley & Sons, Ltd.     

Application of DBS sampling in combination with LC-MS/MS for pharmacokinetic evaluation of a compound with species-specific blood-to-plasma partitioning

Background: Dried blood spot (DBS) sampling in combination with LC-MS/MS has been used increasingly in drug discovery for quantitative analysis to support pharmacokinetic (PK) studies. In this study, we assessed the effect of blood-to-plasma (B:P) partitioning on the bioanalytical performance and PK data acquired by DBS for a compound AMG-1 with species and concentration-dependent B:P ratio. Results: B:P partitioning did not adversely affect bioanalytical performance of DBS for AMG-1. For rat, (B:P ratio of 0.63), PK profiles from DBS and plasma methods were comparable. For dog, concentration-dependence of B:P ratio was observed both in vivo and in vitro. Additional studies demonstrated concentration-dependence of the compound's unbound fraction in plasma, which may contribute to the concentration-dependence of the B:P ratio. Conclusion: DBS is a promising sampling technique for preclinical pharmacokinetic studies. For compounds with high B:P ratio, caution needs to be applied for data comparison and interpretation between matrices.     

The Autism-Spectrum Quotient—Italian Version: A Cross-Cultural Confirmation of the Broader Autism Phenotype

The Autism Spectrum Quotient (AQ) has been used to define the ‘broader’ (BAP), ‘medium’ (MAP) and ‘narrow’ autism phenotypes (NAP). We used a new Italian version of the AQ to test if difference on AQ scores and the distribution of BAP, MAP and NAP in autism parents (n = 245) versus control parents (n = 300) were replicated in a Sicilian sample. Parents of children with autism spectrum conditions scored higher than the control parents on total AQ, social skills and communication subscales, and exhibited higher rates of BAP, MAP and NAP. We conclude that the Italian AQ is a cross-culturally reliable measure of these different phenotypes, and can be used to identify a phenotypic gradient of severity of autistic traits in families. To understand the molecular basis of these phenotypes will require its use in genetic association studies.     

Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings.     

Risk factors for atrial fibrillation in adult patients in long-term observation following surgical closure of atrial septal defect type II

BACKGROUND: The aim of the study was to find the factors predictive for paroxysmal atrial fibrillation (AF) following surgical correction of atrial septal defect type II (ASD t.II). METHODS: 93 patients, who underwent isolated surgical closure of ASD t.II between 1990 and 2001 were included. Follow-up studies were performed 2 - 11 years after surgery. Patients were divided into two groups according to the presence of AF before and after surgery. Group AF (+) consisted of 29 and group AF (-) of 64 patients. All patients underwent echocardiography, electrocardiogram (ECG) at rest, and signal-averaged P-wave duration (PWD) in signal-averaged ECG. The following parameters were assessed in echocardiography: pulmonary artery systolic pressure, left and right atrial dimensions, right ventricular dimension, tricuspid and mitral regurgitation. RESULTS: Paroxysmal AF was observed in 27 patients before surgery and in 29 after surgery. Analyzing all potential risk factors we proved that PWD may independently predict occurrence of postoperative AF. CONCLUSION: PWD may independently predict postoperative AF in long-term follow-up after surgical correction of ASD t.II.     

Trajectories of quality of life recovery and symptom burden after autologous hematopoietic cell transplantation in multiple myeloma

Early autologous hematopoietic cell transplantation (AHCT) with post-transplant maintenance therapy is standard of care in multiple myeloma (MM). While short-term quality of life (QOL) deterioration after AHCT is known, the long-term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT (N = 758), was conducted. FACT-BMT scores up to 4 years post-AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as ‘none/mild’ for scores 0–2 and ‘moderate/severe’ for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1-year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow-up was 6 years (range, 0.4–8.5 years). FACT-BMT scores improved between enrollment and 1-year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1-year, and 32% at 4 years post-AHCT. Predictors of low symptom burden at 1-year included low symptom burden at baseline: OR 2.7 (1.8–4.1), p < 0.0001; older age: OR 2.1 (1.3–3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4–3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT-BMT and subscale scores to population norms by 1-year post-transplant, though many patients continue to report moderate to severe severity in some symptoms at 1-year and beyond.