Structure of the silicon vacancy in 6H-SiC after annealing identified as the carbon vacancy–carbon antisite pair

We investigated radiation-induced defects in neutron-irradiated and subsequently annealed 6H-silicon carbide (SiC) with electron paramagnetic resonance (EPR), the magnetic circular dichroism of the absorption (MCDA), and MCDA-detected EPR (MCDA-EPR). In samples annealed beyond the annealing temperature of the isolated silicon vacancy we observed photoinduced EPR spectra of spin S=1 centers that occur in orientations expected for nearest neighbor pair defects. EPR spectra of the defect on the three inequivalent lattice sites were resolved and attributed to optical transitions between photon energies of 999 and 1075 meV by MCDA-EPR. The resolved hyperfine structure indicates the presence of one single carbon nucleus and several silicon ligand nuclei. These experimental findings are interpreted with help of total energy and spin density data obtained from the standard local-spin density approximation of the density-functional theory, using relaxed defect geometries obtained from the self-consistent charge density-functional theory based tight binding scheme. We have checked several defect models of which only the photoexcited spin triplet state of the carbon antisite–carbon vacancy pair (CSi-VC) in the doubly positive charge state can explain all experimental findings. We propose that the (CSi-VC) defect is formed from the isolated silicon vacancy as an annealing product by the movement of a carbon neighbor into the vacancy

Depleting Components of the THO Complex Causes Increased Telomere Length by Reducing the Expression of the Telomere-Associated Protein Rif1p

Telomere length is regulated mostly by proteins directly associated with telomeres. However, genome-wide analysis of Saccharomyces cerevisiae mutants has revealed that deletion of Hpr1p, a component of the THO complex, also affects telomere length. The THO complex comprises four protein subunits, namely, Tho2p, Hpr1p, Mft1p, and Thp2p. These subunits interplay between transcription elongation and co-transcriptional assembly of export-competent mRNPs. Here we found that the deletion of tho2 or hpr1 caused telomere lengthening by ∼50–100 bps, whereas that of mft1 or thp2 did not affect telomere length. Since the THO complex functions in transcription elongation, we analyzed the expression of telomere-associated proteins in mutants depleted of complex components. We found that both the mRNA and protein levels of RIF1 were decreased in tho2 and hpr1 cells. RIF1 encodes a 1917-amino acid polypeptide that is involved in regulating telomere length and the formation of telomeric heterochromatin. Hpr1p and Tho2p appeared to affect telomeres through Rif1p, as increased Rif1p levels suppressed the telomere lengthening in tho2 and hpr1 cells. Moreover, yeast cells carrying rif1 tho2 or rif1 hpr1 double mutations showed telomere lengths and telomere silencing effects similar to those observed in the rif1 mutant. Thus, we conclude that mutations of components of the THO complex affect telomere functions by reducing the expression of a telomere-associated protein, Rif1p

General practitioners' deprescribing decisions in older adults with polypharmacy: a case vignette study in 31 countries

BACKGROUND: General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries. METHODS: In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions. RESULTS: Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). INTERPRETATION: The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD

Study

Background. Patients use self-care to relieve symptoms of common colds, yet little is known about the prevalence and patterns across Europe. Methods/Design. In a cross-sectional study 27 primary care practices from 14 countries distributed 120 questionnaires to consecutive patients (>= 18 years, any reason for consultation). A 27-item questionnaire asked for patients' self-care for their last common cold. Results. 3,074 patients from 27 European sites participated. Their mean age was 46.7 years, and 62.5% were females. 99% of the participants used >= 1 self-care practice. In total, 527 different practices were reported; the age-standardized mean was 11.5 (+/- SD 6.0) per participant. The most frequent self-care categories were foodstuffs (95%), extras at home (81%), preparations for intestinal absorption (81%), and intranasal applications (53%). Patterns were similar across all sites, while the number of practices varied between and within countries. The most frequent single practices were water (43%), honey (42%), paracetamol (38%), oranges/orange juice (38%), and staying in bed (38%). Participants used 9 times more nonpharmaceutical items than pharmaceutical items. The majority (69%) combined self-care with and without proof of evidence, while <= 1% used only evidence-based items. Discussion. This first cross-national study on self-care for common colds showed a similar pattern across sites but quantitative differences

Self-Care for Common Colds by Primary Care Patients: A European Multicenter Survey on the Prevalence and Patterns of Practices-The COCO Study.

Background. Patients use self-care to relieve symptoms of common colds, yet little is known about the prevalence and patterns across Europe. Methods/Design. In a cross-sectional study 27 primary care practices from 14 countries distributed 120 questionnaires to consecutive patients (≥18 years, any reason for consultation). A 27-item questionnaire asked for patients' self-care for their last common cold. Results. 3,074 patients from 27 European sites participated. Their mean age was 46.7 years, and 62.5% were females. 99% of the participants used ≥1 self-care practice. In total, 527 different practices were reported; the age-standardized mean was 11.5 (±SD 6.0) per participant. The most frequent self-care categories were foodstuffs (95%), extras at home (81%), preparations for intestinal absorption (81%), and intranasal applications (53%). Patterns were similar across all sites, while the number of practices varied between and within countries. The most frequent single practices were water (43%), honey (42%), paracetamol (38%), oranges/orange juice (38%), and staying in bed (38%). Participants used 9 times more nonpharmaceutical items than pharmaceutical items. The majority (69%) combined self-care with and without proof of evidence, while ≤1% used only evidence-based items. Discussion. This first cross-national study on self-care for common colds showed a similar pattern across sites but quantitative differences

Dysregulated expression of the major telomerase components in leukaemic stem cells

Telomere loss is rapid during the progression of chronic myeloid leukaemia (CML) and correlates with prognosis. We therefore sought to measure expression of the major telomerase components (hTR and hTERT) in CD34&lt;sup&gt;+&lt;/sup&gt; cells from CML patients and normal controls, to determine if their altered expression may contribute to telomere attrition &lt;i&gt;in vivo&lt;/i&gt;. High-purity (median 94.1%) &lt;i&gt;BCR-ABL&lt;/i&gt;&lt;sup&gt;+&lt;/sup&gt; CD34&lt;sup&gt;+&lt;/sup&gt; cells from CML (&lt;i&gt;n&lt;/i&gt;=16) and non-CML (&lt;i&gt;n&lt;/i&gt;=14) patients were used. CML samples had a small increase in telomerase activity (TA) compared to normal samples (approximately 1.5-fold, &lt;i&gt;P&lt;/i&gt;=0.004), which was inversely correlated with the percentage of G&lt;sub&gt;0&lt;/sub&gt; cells (&lt;i&gt;P&lt;/i&gt;=0.02) suggesting TA may not be elevated on a cell-to-cell basis in CML. Consistent with this, hTERT mRNA expression was not significantly elevated; however, altered mRNA splicing appeared to play a significant role in determining overall full length, functional hTERT levels. Interestingly, Q-RT-PCR for hTR demonstrated a mean five-fold reduction in levels in the chronic phase (CP) CML samples (&lt;i&gt;P&lt;/i&gt;=0.002), raising the possibility that telomere homeostasis is disrupted in CML. In summary, the molecular events regulating telomerase gene expression and telomere maintenance during the CP of CML may influence the disease progression observed in these patients