Dentists reflect on their problem‐based education and professional satisfaction

Aim: To determine the way in which Malmö University dental graduates perceive their problem‐based dental education and evaluate their professional satisfaction. Method: The first five cohorts (graduating in years 1995–1999) of the problem‐based curriculum were invited to participate. Of 166 graduates, 77% responded to a questionnaire comprising 20 questions on aspects of their dental education, professional situations and interest in postgraduate education. They were asked to rank their perception of their dental education and satisfaction with their professional situation on a visual analogue scale (VAS) with endpoints ranging from ‘Not at all’ (1) to ‘Very well’ (10). For other statements, the markings were made on a Likert scale from 1 (not important/not satisfied) to 5 (very important/very satisfied). There were also open‐ended questions. Results: Most respondents perceived their education to prepare them well for a career in dentistry (median score VAS 8), and 90% rated above six on a VAS for their professional satisfaction as dentists. Importance and satisfaction were highly correlated with principles of the curriculum: holistic view, oral health, lifelong learning, integration between theory and clinic, and clinical competence. Forty‐five per cent of the graduates noted the problem‐based learning approach as the most valuable asset of their education, and 19% cited training in oral surgery as a deficit. Of the respondents, 77% expressed interest in specialist training and 55% in research education. Conclusion: Problem‐based education was perceived to prepare graduates well for their profession, and their professional satisfaction was high.     

The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling

Arsenic in the form of arsenic trioxide (ATO) is used as a therapeutic drug for treatment of acute promyelocytic leukemia (APL). The mechanism by which this agent cures this disease was previously shown to involve direct interactions between ATO and the promyelocytic leukemia protein (PML), as well as accelerated degradation of the APL-associated fusion oncoprotein PML/retinoic acid receptor α (RARA). Here we investigated the fate of PML-generated nuclear structures called PML bodies in ATO-treated cells. We found that ATO inhibits formation of progeny PML bodies while it stabilizes cytoplasmic precursor compartments, referred to as cytoplasmic assemblies of PML and nucleoporins (CyPNs), after cell division. This block in PML body recycling is readily detected at pharmacologic relevant ATO concentrations (0.02-0.5μM) that do not cause detectable cell-cycle defects, and it does not require modification of PML by SUMOylation. In addition, PML and PML/RARA carrying mutations previously identified in ATO-resistant APL patients are impeded in their ability to become sequestered within CyPNs. Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration.     

Sodium current and potassium transient outward current genes in Brugada syndrome: screening and bioinformatics

Background

Brugada syndrome (BrS) is a primary arrhythmia syndrome characterized by the occurrence of malignant ventricular arrhythmias. Previously, the genes SCN1B, SCN3B, MOG1, and KCND3 have been associated with BrS. Recent data from exome screening efforts permit better discrimination between low-frequency genetic variants and true monogenetic disease-causing variants. We aimed to screen the genes SCN1B through SCN4B, MOG1, CAV3, and KCND3 for variations in a population of SCN5A negative Danish and Iranian BrS patients, as well as research prior associations using newly released exome data.

Methods

Screening of all exons and splice sites was performed using Sanger sequencing. Bioinformatic searches were performed in the Single-nucleotide polymorphism database (build 132) and in the National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project (ESP) for both previously published variant-BrS associations and newly uncovered variations within the noted genes.

Results

A total of 42 BrS patients were screened, and 2 different nonsynonymous mutations in SCN1Bb (H162P and R214Q) were found in 2 different Danish patients. The variants were not found in 216 Danish controls, but R214Q was present in ESP data (5 of 841 alleles). No other mutations were found. Previously BrS-associated mutations in KNCD3 and SCN3B were also present in ESP data. This was not the case for MOG1, but a nonsense polymorphism was present in 0.5% of alleles.

Conclusions

Our study supports the association of SCN1Bb with BrS. However, recently released exome data make some of the prior associations of BrS with genes SCN3B, MOG1, and KCND3 less likely.     

Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years

Background

Three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 have been associated with atrial fibrillation (AF) in genome-wide association studies (GWAS). Five additional loci have been associated primarily with the PR interval and subsequently with AF. We aimed to investigate if 8 single nucleotide polymorphisms (SNPs), representing the 8 genomic loci previously linked with AF in genome-wide association studies, were associated with early-onset lone AF.

Methods

We included 209 patients with early-onset lone AF, and a control group consisting of 534 individuals free of AF. The 8 SNPs were genotyped using TaqMan assays (Applied Biosystems, Foster City, CA).

Results

Three SNPs were found to be significantly associated with early-onset lone AF: rs2200733 closest to PITX2 (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.27; P = 0.004), rs3807989 near to CAV1 (OR 1.35; 95% CI, 1.06-1.72; P = 0.015), and rs11047543 near to SOX5 (OR 1.70; 95% CI, 1.18-2.44; P = 0.004). When correcting for multiple testing, rs2200733 and rs11047543 were still significantly associated with AF.

Conclusions

Three SNPs, rs2200733 (4q25), rs3807989 (7p31), and rs11047543 (12p12), were associated with early-onset lone AF. All 3 SNPs are positioned close to genes that in previous studies have been demonstrated to be important for cardiac morphology/development, thereby suggesting a link between these SNPs and structural heart disease. Our results however, indicate that variants in these 3 loci are associated with AF through mechanisms that do not involve major structural abnormalities in the heart.     

Patterns of subjective quality of life among older adults in rural Vietnam and Indonesia

Aim: This paper aims to assess the subjective quality of life (SQOL) and its correlates among older adults in rural communities of Vietnam and Indonesia. Methods: The paper uses the data from the INDEPTH/WHO Study on global aging and adult health (SAGE). The study was carried out in the FilaBavi Health and Demographic Surveillance System (HDSS) site in Vietnam and in Purworejo HDSS in Indonesia. All people aged 50 years and over who lived in these two HDSS areas were surveyed. Face‐to‐face household interviews were carried out by trained surveyors using the standardized summary version of the INDEPTH/WHO SAGE questionnaire. The SQOL was assessed by asking the respondents “How would you rate your overall quality of life?” The response set was a five‐point scale where 1 = Very good, 2 = Good, 3 = Moderate, 4 = Bad, 5 = Very bad. Results: In both countries, the SQOL was reported to be higher among (i) men; (ii) people with higher education; (iii) people who were in a marital partnership; (iv) people who lived with other family members; and (v) those with higher economic status, compared with that in those of other category(ies) of the same characteristic. In Vietnam, people who belonged to the second to fifth economic quintiles and had more than 6 years of education were sevenfold more likely to report very good/good quality of life compared with those who belonged to the first economic quintile (poorest) and had no formal education. The corresponding figure was 2.7 for Indonesia. Conclusions: The patterns of sociodemographic determinants of SQOL show that inequality in quality of life exists among older adults in the two study settings. Geriatr Gerontol Int 2012; 12: 397–404.     

Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality

Background

It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population.

Objective

To determine whether long-term PSAV improves classification of PCa risk and mortality in the general population.

Design, setting, and participants

We studied 503 men aged 30–80 yr, with and without PCa, who had repeated PSA measurements over 20 yr and up to 28 yr before PCa diagnosis. These were selected from among 7455 men in the Copenhagen City Heart Study, a prospective, general population study with follow-up from 1981 through 2010. Results were subsequently applied to all 1 351 441 men aged 40–80 yr living in Denmark from 1997 through 2006.

Outcome measurements and statistical analysis

PCa risk and mortality were assessed using Cox regression. Improvement in risk classification was assessed using the net reclassification index (NRI).

Results

Age-adjusted hazard ratios for PCa risk and mortality were 2.7–5.3 and 2.3–3.4, respectively, for long-term PSAV when added to models already including baseline PSA values. For PCa risk and mortality, adding long-term PSAV to models already including baseline PSA values and age yielded continuous NRIs of 98–99% and 56–106%, respectively. Used on a nationwide scale (eg, for men aged 60–64 yr), long-term PSAV >0.35 versus ≤0.35 ng/ml per year appropriately reclassified 128 of 10 000 men with PCa and 8095 of 10 000 men with no PCa. Correspondingly, inappropriately reclassified were 49 of 10 000 men with PCa and 1658 of 10 000 men with no PCa.

Conclusions

Long-term PSAV in addition to baseline PSA value improves classification of PCa risk and mortality. Applying long-term PSAV nationwide, the ratio of appropriately to inappropriately classified men would typically be 5:1.     

The Copeland resurfacing humeral head implant does not restore humeral head anatomy. A retrospective study

Purpose

Recently, there has been concern that the Copeland resurfacing humeral head implant (RHHI) leaves the shoulder joint overstuffed. The purpose of this study was in a selected cohort of patients operated with a Copeland RHHI (1) to evaluate the Length of the Gleno-Humeral Offset (LGHO), (2) to assess the patient-reported quality of life and functional outcome measured by Western Ontario Osteoarthritis of the Shoulder Index (WOOS) and (3) to determine the number of revisions in the cohort.

Methods

Pre- and postoperative radiographs were retrieved from 71 of 91 possible patients operated with a Copeland RHHI from 2005 to 2009. The cohort consisted of 30 males and 41 females at a mean age of 61 (38–89) years. One radiologist measured the LGHO and performed double measurements. The WOOS score 1 year after surgery and the number of revisions from all patients operated with a Copeland RHHI in Denmark was requested from the Danish Shoulder Arthroplasty Registry.

Results

The mean LGHO was 4.99 ± 0.53 cm before surgery and 5.39 ± 0.58 cm after surgery, (p < 0.001). 95 % limits of agreement for measurements of LGHO were ± 0.11 cm. One year after surgery, the WOOS score was 67 for the cohort and 64 for all patients operated with a Copeland RHHI in Denmark. 13 of 71 RHHI in the cohort were revised.

Conclusion

The Copeland RHHI causes significantly increased LGHO and leads to overstuffing in the shoulder joint. The WOOS score in the cohort was comparable to that for all other Danish patients operated with a Copeland RHHI.