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1.
Age Ageing ; 53(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38783755

ABSTRACT

BACKGROUND: Patients with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia are underrepresented in specialist palliative home care (SPHC). However, the complexity of their conditions requires collaboration between general practitioners (GPs) and SPHC teams and timely integration into SPHC to effectively meet their needs. OBJECTIVE: To facilitate joint palliative care planning and the timely transfer of patients with advanced chronic non-malignant conditions to SPHC. METHODS: A two-arm, unblinded, cluster-randomised controlled trial. 49 GP practices in northern Germany were randomised using web-based block randomisation. We included patients with advanced CHF, COPD and/or dementia. The KOPAL intervention consisted of a SPHC nurse-patient consultation followed by an interprofessional telephone case conference between SPHC team and GP. The primary outcome was the number of hospital admissions 48 weeks after baseline. Secondary analyses examined the effects on health-related quality of life and self-rated health status, as measured by the EuroQol 5D scale. RESULTS: A total of 172 patients were included in the analyses. 80.4% of GP practices had worked with SHPC before, most of them exclusively for cancer patients. At baseline, patients reported a mean EQ-VAS of 48.4, a mean quality of life index (EQ-5D-5L) of 0.63 and an average of 0.80 hospital admissions in the previous year. The intervention did not significantly reduce hospital admissions (incidence rate ratio = 0.79, 95%CI: [0.49, 1.26], P = 0.31) or the number of days spent in hospital (incidence rate ratio = 0.65, 95%CI: [0.28, 1.49], P = 0.29). There was also no significant effect on quality of life (∆ = -0.02, 95%CI: [-0.09, 0.05], P = 0.53) or self-rated health (∆ = -2.48, 95%CI: [-9.95, 4.99], P = 0.51). CONCLUSIONS: The study did not show the hypothesised effect on hospitalisations and health-related quality of life. Future research should focus on refining this approach, with particular emphasis on optimising the timing of case conferences and implementing discussed changes to treatment plans, to improve collaboration between GPs and SPHC teams.


Subject(s)
Heart Failure , Palliative Care , Primary Health Care , Pulmonary Disease, Chronic Obstructive , Quality of Life , Humans , Palliative Care/methods , Male , Female , Aged , Germany , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Aged, 80 and over , Heart Failure/therapy , Heart Failure/diagnosis , Dementia/therapy , Chronic Disease , Home Care Services , Patient Care Team , Time Factors , Interdisciplinary Communication , Delivery of Health Care, Integrated/organization & administration
2.
Ann Palliat Med ; 12(6): 1175-1186, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37872126

ABSTRACT

BACKGROUND: Worldwide, progressive chronic, non-malignant diseases are highly prevalent. Especially with increasing age, they are characterised by high hospitalisation rates and high healthcare costs. Improved interprofessional collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams might reduce hospitalisation while improving symptoms and quality of life, or preventing them from deterioration. The aim of this study was to examine the cost-effectiveness of a newly developed intervention in patients with advanced chronic, non-malignant diseases consisting of a structured palliative care nurse-patient consultation followed by an interprofessional telephone case conference. METHODS: The analysis was based on data from 172 participants of the KOPAL multi-centre, cluster randomised controlled trial. Patients with advanced congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or dementia were randomised into intervention group (IG) and control group (CG, usual care). Cost-effectiveness was examined over 48 weeks from a societal and healthcare payer's perspective. Effects were quantified as quality-adjusted life years (QALYs, EQ-5D-5L). Incremental cost-effectiveness ratios were calculated and cost-effectiveness acceptability curves were constructed. RESULTS: Baseline imbalances in costs and effects could be observed between IG and CG. After adjusting for these imbalances and compared to the CG, mean costs in the IG were non-significantly higher from a societal and lower from a payer's perspective. On the effect side, the IG had marginally lower mean QALYs. The results were characterized by high statistical uncertainty, indicated by large confidence intervals for the cost and effect differences between groups and probabilities of cost-effectiveness between 18% and 65%, depending on the perspective and willingness-to-pay. CONCLUSIONS: Based on the results of this study, the cost-effectiveness of the KOPAL intervention was uncertain. The results highlighted (methodological) challenges of economic evaluations in patients with chronic, non-malignant diseases related to sample size, heterogeneity of participants, and the way the intervention effectiveness is typically captured in economic evaluations.


Subject(s)
Palliative Care , Quality of Life , Humans , Cost-Benefit Analysis , Chronic Disease , Referral and Consultation , Quality-Adjusted Life Years
3.
PLoS Genet ; 19(9): e1010945, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37747878

ABSTRACT

Facultative heterochromatin controls development and differentiation in many eukaryotes. In metazoans, plants, and many filamentous fungi, facultative heterochromatin is characterized by transcriptional repression and enrichment with nucleosomes that are trimethylated at histone H3 lysine 27 (H3K27me3). While loss of H3K27me3 results in derepression of transcriptional gene silencing in many species, additional up- and downstream layers of regulation are necessary to mediate control of transcription in chromosome regions enriched with H3K27me3. Here, we investigated the effects of one histone mark on histone H4, namely H4K20me3, in the fungus Zymoseptoria tritici, a globally important pathogen of wheat. Deletion of kmt5, the gene encoding the sole methyltransferase responsible for H4K20 methylation, resulted in global derepression of transcription, especially in regions of facultative heterochromatin. Derepression in the absence of H4K20me3 not only affected known genes but also a large number of novel, previously undetected transcripts generated from regions of facultative heterochromatin on accessory chromosomes. Transcriptional activation in kmt5 deletion strains was accompanied by a complete loss of Ash1-mediated H3K36me3 and chromatin reorganization affecting H3K27me3 and H3K4me2 distribution in regions of facultative heterochromatin. Strains with H4K20L, M or Q mutations in the single histone H4 gene of Z. tritici recapitulated these chromatin changes, suggesting that H4K20me3 is important for Ash1-mediated H3K36me3. The ∆kmt5 mutants we obtained were more sensitive to genotoxic stressors than wild type and both, ∆kmt5 and ∆ash1, showed greatly increased rates of accessory chromosome loss. Taken together, our results provide insights into an unsuspected mechanism involved in the assembly and maintenance of facultative heterochromatin.


Subject(s)
Heterochromatin , Histones , Heterochromatin/genetics , Histones/genetics , Histones/metabolism , Chromatin , Nucleosomes , Methylation
4.
J Am Med Dir Assoc ; 24(5): 609-618.e6, 2023 05.
Article in English | MEDLINE | ID: mdl-36898411

ABSTRACT

OBJECTIVE: To investigate proportions of hospitalized nursing home residents during periods of increased vulnerability, ie, the first 6 months after institutionalization and the last 6 months before death, and comparing the figures between Germany and the Netherlands. DESIGN: Systematic review, registered in PROSPERO (CRD42022312506). SETTING AND PARTICIPANTS: Newly admitted or deceased residents. METHODS: We searched MEDLINE via PubMed, EMBASE, and CINAHL from inception through May 3, 2022. We included all observational studies that reported the proportions of all-cause hospitalizations among German or Dutch nursing home residents during these defined vulnerable periods. Study quality was assessed using the Joanna Briggs Institute's tool. We assessed study and resident characteristics and outcome information and descriptively reported them separately for both countries. RESULTS: We screened 1856 records for eligibility and included 9 studies published in 14 articles (Germany: 8; Netherlands: 6). One study for each country investigated the first 6 months after institutionalization. A total of 10.2% of the Dutch and 42.0% of the German nursing home residents were hospitalized during this time. Overall, 7 studies reported on in-hospital deaths, with proportions ranging from 28.9% to 29.5% for Germany and from 1.0% to 16.3% for the Netherlands. Proportions for hospitalization in the last 30 days of life ranged from 8.0% to 15.7% (Netherlands: n = 2) and from 48.6% to 58.0% (Germany: n = 3). Only German studies assessed the differences by age and sex. Although hospitalizations were less common at older ages, they were more frequent in male residents. CONCLUSIONS AND IMPLICATIONS: During the observed periods, the proportion of nursing homes residents being hospitalized differed greatly between Germany and the Netherlands. The higher figures for Germany can probably be explained by differences in the long-term care systems. There is a lack of research, especially for the first months after institutionalization, and future studies should examine the care processes of nursing home residents following acute events in more detail.


Subject(s)
Long-Term Care , Nursing Homes , Humans , Male , Hospitalization , Ethnicity , Germany
5.
Fungal Genet Biol ; 162: 103729, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35944835

ABSTRACT

γ-Tubulin ring complexes (γ-TuRC) mediate nucleation and anchorage of microtubules (MTs) to microtubule organizing centers (MTOCs). In fungi, the spindle pole body (SPB) is the functional equivalent of the centrosome, which is the main MTOC. In addition, non-centrosomal MTOCs (ncMTOCs) contribute to MT formation in some fungi like Schizosaccharomyces pombe and Aspergillus nidulans. In A. nidulans, MTOCs are anchored at septa (sMTOC) and share components of the outer plaque of the SPB. Here we show that the Neurospora crassa SPB is embedded in the nuclear envelope, with the γ-TuRC targeting proteins PCP-1Pcp1/PcpA located at the inner plaque and APS-2Mto1/ApsB located at the outer plaque of the SPB. PCP-1 was a specific component of nuclear MTOCs, while APS-2 was also present at the septal pore. Although γ-tubulin was only detected at the nucleus, spontaneous MT nucleation occurred in the apical and subapical cytoplasm during recovery from benomyl-induced MT depolymerization experiments. There was no evidence for MT nucleation at septa. However, without benomyl treatment MT plus-ends were organized in the septal pore through MTB-3EB1. Those septal MT plus ends polymerized MTs from septa in interphase cells Thus we conclude that the SPB is the only MT nucleation site in N. crassa, but the septal pore aids the MT network arrangement through the anchorage of the MT plus-ends through a pseudo-MTOC.


Subject(s)
Carrier Proteins , Fungal Proteins , Microtubule-Associated Proteins , Neurospora crassa , Benomyl/metabolism , Carrier Proteins/metabolism , Fungal Proteins/metabolism , Microtubule-Associated Proteins/metabolism , Microtubule-Organizing Center/metabolism , Microtubules/metabolism , Neurospora crassa/genetics , Neurospora crassa/metabolism , Spindle Pole Bodies/metabolism , Tubulin/genetics
6.
Eur J Gen Pract ; 28(1): 209-216, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35819357

ABSTRACT

BACKGROUND: Little literature exists on emergencies within primary care offices. OBJECTIVES: We aimed to study the occurrence of emergencies and confidence in dealing with them among primary care physicians (PCPs) in Germany. METHODS: We conducted a cross-sectional study among all PCPs with licences to practice with an own office (n = 915) in a northwestern region in Germany in 2019. Participants were asked to estimate the frequency and type of emergencies that occurred in the last 12 months in their office and about their confidence in managing emergency situations. RESULTS: Answers from 375 PCPs could be analysed (response: 41.0%); 95.7% reported at least one emergency in their office within the last 12 months (mean 12.9). PCPs from rural offices reported more emergencies (on average 13.7 vs. 9.6). Acute coronary syndrome, cardiac arrhythmia and dyspnoea were the most common emergencies. A greater likelihood of feeling more confident in managing medical emergencies was found among male physicians, general internists, PCPs additionally qualified as emergency physicians and those with previous training in the emergency department and intensive care unit. In contrast, more general practitioners felt secure treating paediatric emergencies than general internists (highest level of confidence 22.1% vs. 16.3%). CONCLUSION: In Germany, emergencies in primary care offices occur on average once a month and more often in rural than urban areas. While most PCPs are confident in managing medical emergencies, some differences related to the training path became apparent. Ongoing training programmes may be tailored to improve emergency skills.


Subject(s)
Emergencies , Health Personnel , Child , Cross-Sectional Studies , Germany , Humans , Male , Primary Health Care
7.
BMJ Open ; 12(7): e059440, 2022 07 25.
Article in English | MEDLINE | ID: mdl-35879008

ABSTRACT

INTRODUCTION: Progressive chronic, non-malignant diseases (CNMD) like congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia are of growing relevance in primary care. Most of these patients suffer from severe symptoms, reduced quality of life and increased numbers of hospitalisations. Outpatient palliative care can help to reduce hospitalisation rate by up to 50%. Due to the complex medical conditions and prognostic uncertainty of the course of CNMD, early interprofessional care planning among general practitioners who provide general palliative care and specialist palliative home care (SPHC) teams seems mandatory. The KOPAL study (a concept for strenghtening interprofessional collaboration for patients with palliative care needs) will test the effectiveness of a SPHC nurse-patient consultation followed by an interprofessional telephone case conference. METHODS AND ANALYSIS: Multicentre two-arm cluster randomised controlled trial KOPAL with usual care as control arm. The study is located in Northern Germany and aims to recruit 616 patients in 56 GP practices (because of pandemic reasons reduced to 191 participants). Randomisation will take place on GP practice level immediately after inclusion (intervention group/control group). Allocation concealment is carried out on confirmation of participation. Patients diagnosed with CHF (New York Heart Association (NYHA) classification 3-4), COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage classification 3-4, group D) or dementia GDS stage 4 or above). Primary outcome is a reduced hospital admission within 48 weeks after baseline, secondary outcomes include symptom burden, quality of life and health costs. The primary analysis will follow the intention-to-treat principle. Intervention will be evaluated after the observation period using qualitative methods. ETHICS AND DISSEMINATION: The responsible ethics committees of the cooperating centres approved the study. All steps of data collection, quality assurance and data analysis will continuously be monitored. The concept of KOPAL could serve as a blueprint for other regions and meet the challenges of geographical equity in end-of-life care. TRIAL REGISTRATION NUMBER: DRKS00017795; German Clinical Trials Register.


Subject(s)
Dementia , Heart Failure , Home Care Services , Pulmonary Disease, Chronic Obstructive , Chronic Disease , Heart Failure/therapy , Humans , Multicenter Studies as Topic , Palliative Care/methods , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life , Randomized Controlled Trials as Topic , Referral and Consultation , Telephone
8.
Methods Mol Biol ; 2529: 3-40, 2022.
Article in English | MEDLINE | ID: mdl-35733008

ABSTRACT

Dynamic posttranslational modifications to canonical histones that constitute the nucleosome (H2A, H2B, H3, and H4) control all aspects of enzymatic transactions with DNA. Histone methylation has been studied heavily for the past 20 years, and our mechanistic understanding of the control and function of individual methylation events on specific histone arginine and lysine residues has been greatly improved over the past decade, driven by excellent new tools and methods. Here, we will summarize what is known about the distribution and some of the functions of protein methyltransferases from all major eukaryotic supergroups. The main conclusion is that protein, and specifically histone, methylation is an ancient process. Many taxa in all supergroups have lost some subfamilies of both protein arginine methyltransferases (PRMT) and the heavily studied SET domain lysine methyltransferases (KMT). Over time, novel subfamilies, especially of SET domain proteins, arose. We use the interactions between H3K27 and H3K36 methylation as one example for the complex circuitry of histone modifications that make up the "histone code," and we discuss one recent example (Paramecium Ezl1) for how extant enzymes that may resemble more ancient SET domain KMTs are able to modify two lysine residues that have divergent functions in plants, fungi, and animals. Complexity of SET domain KMT function in the well-studied plant and animal lineages arose not only by gene duplication but also acquisition of novel DNA- and histone-binding domains in certain subfamilies.


Subject(s)
Histones , Protein Methyltransferases , Animals , Arginine/metabolism , Eukaryota/genetics , Eukaryota/metabolism , Histone-Lysine N-Methyltransferase/chemistry , Histones/metabolism , Lysine/metabolism , Methylation , Methyltransferases/genetics , Methyltransferases/metabolism , Protein Methyltransferases/genetics , Protein Methyltransferases/metabolism , Protein Processing, Post-Translational
9.
Maturitas ; 153: 33-40, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34654526

ABSTRACT

OBJECTIVES: While gout is a well-known entity, little research has been conducted on its pathophysiology. There is growing evidence that women with hyperuricemia are at higher cardiovascular risk than men with hyperuricemia. We aim to evaluate whether gender-specific cut-offs should be considered. STUDY DESIGN: Cross-sectional study (the German Health Interview and Examination Survey for Adults; DEGS1). MAIN OUTCOME MEASURES: Self-reported gout or hyperuricemia and uric acid level. RESULTS: Of 6,918 participants (mean age 47.2 years; 50.5% females), 9.7% had had a diagnosis of hyperuricemia or gout at least once in their lifetime. Men were nearly twice as often affected as women (12.9 vs. 6.5%). In women, the prevalence of cardiovascular and renal diseases increased with higher uric acid level to a much greater extent than in men. This association remained in multivariate analyses. CONCLUSIONS: No commonly accepted cut-off value for uric acid has been established. Overall, women were at lower risk of hyperuricemia. However, women were at higher risk of having cardiovascular and renal comorbidities, even at lower uric acid levels. Our results are in line with the accumulating evidence that we should consider gender in gout and hyperuricemia.


Subject(s)
Gout/epidemiology , Hyperuricemia/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Comorbidity , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Female , Germany/epidemiology , Gout/complications , Humans , Hyperuricemia/complications , Male , Middle Aged , Prevalence , Risk Factors , Uric Acid/blood , Young Adult
10.
Int J Mol Sci ; 22(12)2021 Jun 10.
Article in English | MEDLINE | ID: mdl-34200775

ABSTRACT

Fusarium graminearum, the primary cause of Fusarium head blight (FHB) in small-grain cereals, demonstrates remarkably variable levels of aggressiveness in its host, producing different infection dynamics and contrasted symptom severity. While the secreted proteins, including effectors, are thought to be one of the essential components of aggressiveness, our knowledge of the intra-species genomic diversity of F. graminearum is still limited. In this work, we sequenced eight European F. graminearum strains of contrasting aggressiveness to characterize their respective genome structure, their gene content and to delineate their specificities. By combining the available sequences of 12 other F. graminearum strains, we outlined a reference pangenome that expands the repertoire of the known genes in the reference PH-1 genome by 32%, including nearly 21,000 non-redundant sequences and gathering a common base of 9250 conserved core-genes. More than 1000 genes with high non-synonymous mutation rates may be under diverse selection, especially regarding the trichothecene biosynthesis gene cluster. About 900 secreted protein clusters (SPCs) have been described. Mostly localized in the fast sub-genome of F. graminearum supposed to evolve rapidly to promote adaptation and rapid responses to the host's infection, these SPCs gather a range of putative proteinaceous effectors systematically found in the core secretome, with the chloroplast and the plant nucleus as the main predicted targets in the host cell. This work describes new knowledge on the intra-species diversity in F. graminearum and emphasizes putative determinants of aggressiveness, providing a wealth of new candidate genes potentially involved in the Fusarium head blight disease.


Subject(s)
Fusarium/genetics , Genome, Fungal , Genomics/methods , Host-Pathogen Interactions , Plant Diseases/genetics , Polymorphism, Single Nucleotide , Triticum/microbiology , Biological Evolution , Computational Biology , Fusarium/pathogenicity , Plant Diseases/immunology , Plant Diseases/microbiology , Quantitative Trait Loci
11.
Front Oncol ; 11: 691197, 2021.
Article in English | MEDLINE | ID: mdl-34150662

ABSTRACT

BACKGROUND: In 2020, around 1.4 million new prostate cancer (PCa) cases were recorded worldwide. Early detection of PCa by prostate-specific antigen (PSA) screening remains debated, leading to different specialist-specific recommendations in PCa guidelines. This study aimed to assess attitudes toward and use of PSA testing among urologists in Germany and general practitioners (GPs) in Lower Saxony (Germany). METHODS: A nationwide questionnaire was sent to urologists via the mailing lists of the Professional Association of German Urologists and the German Urological Society. A version of the questionnaire for GPs was sent to email addresses via the Association of Statutory Health Insurance Physicians Lower Saxony. The online questionnaires covered use of PSA testing, information communication, handling of test results, and handling of/knowledge about national and international guidelines and recommendations on early detection of PCa. Statistical analysis was performed at a descriptive level. RESULTS: In total, 432 of 6,568 urologists (6.6%) and 96 of 1,579 GPs (6.1%) participated in this survey. Urologists and GPs differed in their attitudes and approaches toward PSA testing. Most urologists (86.8%, n=375) judged the test as "very meaningful" or "meaningful", compared with 52.1% (n=50) of GPs. Almost two-thirds of the urologists (64.4%, n=278) viewed the PCa mortality reduction by PSA testing as proven, compared with one-fifth of GPs (20.8%, n=20). Almost 80% of male urologists (79.9%, n=291) indicated that they would undergo a PSA test in the future (again), compared with 55.1% of male GPs (n=38). In addition, 56.3% (n=243) of urologists stated that "considerably more than half" or "almost all" men aged 45 years or older received a PSA test, compared with 19.8% (n=19) of GPs. CONCLUSIONS: Urologists are more convinced about the PSA test than GPs. PSA testing is therefore used more often in urological settings, although the preselected patient population must be considered. In accordance with specialist-specific recommendations, GPs show a more reserved approach toward PSA testing. Instead of focusing on different attitudes and recommendations on PSA testing, the exchange between specialist groups should be improved to achieve a consistent approach to PSA testing.

12.
BMC Fam Pract ; 22(1): 75, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33858351

ABSTRACT

BACKGROUND: The primary objective was to describe outpatient treatment of epistaxis among different physicians based on a large patient population over a period of 10 years. The secondary objective was to evaluate the value of the practice fee as an instrument of allocation in patients with epistaxis. METHODS: Anonymized statutory health insurance data (AOK Lower Saxony) of patients with a diagnosis of epistaxis treated between 2007 and 2016 were examined. Demographic data, accompanying diagnoses, medication and involved medical groups (general practitioners (GP), pediatricians, ear, nose and throat (ENT) specialists or other) were analyzed. Furthermore, we assessed whether the use of specialist groups changed after abolition of the practice fee in 2013. RESULTS: Epistaxis was responsible for 302,782 cases (160,963 patients). The distribution of cases was slightly in favor of ENT specialists vs. GP (119,170 vs. 110,352). The cases seen by GP and ENT specialists were comparable with regard to age and sex distribution. Hypertension, atrial fibrillation/flutter and an antithrombotic therapy were slightly more common among cases consulting a GP. The GP recorded more co-diagnoses than the ENT. The use of outpatient care and the proportions of the involved physicians scarcely fluctuated during the study period. Overall, 23,118 patients (14.4%) were diagnosed by both, GP and ENT during a relatively short time period. The practice fee remuneration had no impact on the consultation of the physician groups. CONCLUSION: The outpatient treatment of epistaxis constitutes a considerable medical and economic burden in Germany. Strengthening the primary medical sector (GP-centered care) is necessary to reach the goal of initially directing patients to primary care, providing specialists more time for severe cases and reducing the impact on public health balance sheets.


Subject(s)
Epistaxis , General Practitioners , Data Analysis , Epistaxis/epidemiology , Epistaxis/therapy , Humans , Primary Health Care , Secondary Care
13.
PLoS Genet ; 17(3): e1009448, 2021 03.
Article in English | MEDLINE | ID: mdl-33750960

ABSTRACT

DNA methylation is found throughout all domains of life, yet the extent and function of DNA methylation differ among eukaryotes. Strains of the plant pathogenic fungus Zymoseptoria tritici appeared to lack cytosine DNA methylation (5mC) because gene amplification followed by Repeat-Induced Point mutation (RIP) resulted in the inactivation of the dim2 DNA methyltransferase gene. 5mC is, however, present in closely related sister species. We demonstrate that inactivation of dim2 occurred recently as some Z. tritici isolates carry a functional dim2 gene. Moreover, we show that dim2 inactivation occurred by a different path than previously hypothesized. We mapped the genome-wide distribution of 5mC in strains with or without functional dim2 alleles. Presence of functional dim2 correlates with high levels of 5mC in transposable elements (TEs), suggesting a role in genome defense. We identified low levels of 5mC in strains carrying non-functional dim2 alleles, suggesting that 5mC is maintained over time, presumably by an active Dnmt5 DNA methyltransferase. Integration of a functional dim2 allele in strains with mutated dim2 restored normal 5mC levels, demonstrating de novo cytosine methylation activity of Dim2. To assess the importance of 5mC for genome evolution, we performed an evolution experiment, comparing genomes of strains with high levels of 5mC to genomes of strains lacking functional dim2. We found that presence of a functional dim2 allele alters nucleotide composition by promoting C to T transitions (C→T) specifically at CpA (CA) sites during mitosis, likely contributing to TE inactivation. Our results show that 5mC density at TEs is a polymorphic trait in Z. tritici populations that can impact genome evolution.


Subject(s)
Ascomycota/enzymology , Ascomycota/genetics , DNA (Cytosine-5-)-Methyltransferase 1/deficiency , Evolution, Molecular , Mutation Rate , Mutation , 5-Methylcytosine/metabolism , Alleles , Ascomycota/classification , Ascomycota/isolation & purification , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Geography , Mitosis , Phylogeography , Quantitative Trait Loci
14.
Fam Pract ; 38(3): 265-271, 2021 06 17.
Article in English | MEDLINE | ID: mdl-33251543

ABSTRACT

BACKGROUND: A shortage of general practitioners (GPs) is common to many European countries. To counteract this, it is essential to understand the factors that encourage or discourage medical students from choosing to become a GP. OBJECTIVE: To evaluate medical students' attitudes towards general practice and to identify factors that discourage them from considering a career as a GP. METHODS: In this multinational cross-sectional online survey, 29 284 students from nine German, four Austrian and two Slovenian universities were invited to answer a questionnaire consisting of 146 closed and 13 open-ended items. RESULTS: Of the 4486 students that responded (response rate: 15.3%), 3.6% wanted to become a GP, 48.1% were undecided and 34.6% did not want to be a GP. Significant predictors for interest in becoming a GP were higher age [odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.10], positive evaluation of the content of a GP's work (OR = 4.44; 95% CI = 3.26-6.06), organizational aspects (OR = 1.42; 95% CI = 1.13-1.78), practical experience of general practice (OR = 1.66; 95% CI = 1.08-2.56) and the country of the survey [Slovenian versus German students (Reference): OR = 2.19; 95% CI = 1.10-4.38; Austrian versus German students (Reference): OR = 0.50; 95% CI = 0.32-0.79]. CONCLUSION: Strategies to convince undecided students to opt for a career as a GP should include a positive representation of a GP's work and early and repeated experience of working in a general practice during medical school.


Subject(s)
General Practice , General Practitioners , Students, Medical , Attitude , Career Choice , Cross-Sectional Studies , Humans , Surveys and Questionnaires
15.
Phytopathology ; 111(7): 1064-1079, 2021 07.
Article in English | MEDLINE | ID: mdl-33200960

ABSTRACT

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option available.


Subject(s)
Fusarium , Fusarium/genetics , Phylogeny , Plant Diseases , Plants
16.
BMC Fam Pract ; 21(1): 270, 2020 12 17.
Article in English | MEDLINE | ID: mdl-33334312

ABSTRACT

BACKGROUND: There is wide variation in clinical practice for the early detection of prostate cancer, not least because of the ongoing debate about the benefits of prostate-specific antigen (PSA) testing. In this study, we aimed to assess the approaches, attitudes, and knowledge of general practitioners (GPs) regarding PSA testing in primary care in the Netherlands, particularly regarding recommendations for prostate cancer. METHODS: Questionnaire surveys were sent to 179 GPs in the north-east of the Netherlands, of which 65 (36%) were completed and returned. We also surveyed 23 GPs attending a postgraduate train-the-trainer day (100%). In addition to demographic data and practice characteristics, the 31-item questionnaire covered the attitudes, clinical practice, adherence to PSA screening recommendations, and knowledge concerning the recommendations for prostate cancer early detection. Statistical analysis was limited to the descriptive level. RESULTS: Most GPs (95%; n = 82) stated that they had at least read the Dutch GP guideline, but just half (50%; n = 43) also stated that they knew the content. Almost half (46%; n = 39) stated they would offer detailed counseling before ordering a PSA test to an asymptomatic man requesting a test. Overall, prostate cancer screening was reported to be of minor importance compared to other types of cancer screening. CONCLUSIONS: Clinical PSA testing in primary care in this region of the Netherlands seems generally to be consistent with the relevant guideline for Dutch GPs that is restrictive to PSA testing. The next step will be to further evaluate the effects of the several PSA testing strategies.


Subject(s)
General Practitioners , Prostatic Neoplasms , Early Detection of Cancer , Humans , Male , Mass Screening , Netherlands , Practice Patterns, Physicians' , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis
17.
Sensors (Basel) ; 20(22)2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33238554

ABSTRACT

Tribological experiments (i.e., characterizing the friction and wear behavior of materials) are crucial for determining their potential areas of application. Automating such tests could hence help speed up the development of novel materials and coatings. Here, we utilize convolutional neural networks (CNNs) to automate a common experimental setup whereby an endoscopic camera was used to measure the contact area between a rubber sample and a spherical counterpart. Instead of manually determining the contact area, our approach utilizes a U-Net-like CNN architecture to automate this task, creating a much more efficient and versatile experimental setup. Using a 5× random permutation cross validation as well as additional sanity checks, we show that we approached human-level performance. To ensure a flexible and mobile setup, we implemented the method on an NVIDIA Jetson AGX Xavier development kit where we achieved ~18 frames per second by employing mixed-precision training.

18.
Article in English | MEDLINE | ID: mdl-33003384

ABSTRACT

The frequency of contacts of nursing home residents with medical specialists is lower compared to the general population of the same age group in Germany. The aim of this study was to assess general practitioners' (GPs) views on specialist care needs of nursing home residents, on questions of qualification and care coordination. A cross-sectional study was conducted with a postal questionnaire among a representative sample of 1121 GPs in north-western Germany in 2018. The perceptions of GPs about the relative importance of the type of specialist care that is required in nursing homes was assessed on a five-point Likert scale (0 = very low to 4 = very high). A total of 375 GPs (response 33.5%; mean age 54.4 years; 57.6% male) participated in the survey. GPs assessed care needs as highest for neurologists and psychiatrists (68.7%) and lowest for gynecologists (6.5%). Almost all respondents (96.2%) strongly agreed that medical care for nursing home residents should be coordinated by GPs and that GPs should initiate the referral for further specialist care when required (87.5%). A minority (25.7%) agreed that quality of medical care would improve when care for a nursing home was provided by only one GP practice. GPs perceive the needs of nursing home residents for specialist care as high only in relation to care by neurologists and psychiatrists. GPs consider their own coordination function for medical care in nursing homes as very important.


Subject(s)
General Practitioners , Health Services Needs and Demand , Homes for the Aged/organization & administration , Nursing Homes/organization & administration , Specialization , Cross-Sectional Studies , Female , General Practitioners/statistics & numerical data , Germany , Humans , Male , Middle Aged , Needs Assessment , Surveys and Questionnaires
19.
BMC Health Serv Res ; 20(1): 716, 2020 Aug 04.
Article in English | MEDLINE | ID: mdl-32753058

ABSTRACT

BACKGROUND: Provision of ambulatory care by medical specialists for nursing home residents (NHR) is discussed to be inadequate in Germany, however with only incomplete evidence on this topic. We wanted to know whether the transition to a nursing home is associated with a general decrease in medical specialist care and therefore compared contact rates before and after institutionalization. METHODS: Claims data of 18,779 newly admitted NHR in 2013 were followed for the whole year prior to and up to two years after admission. The frequencies of contacts to specialists were assessed and stratified by sex, age, care level, dementia diagnosis and chronic conditions. Multivariate analyses were conducted to identify predictors for contacts to specialists. RESULTS: One year after institutionalization the most pronounced decrease was found in contacts with ophthalmologists (38.4% vs. 30.6%) whereas with most other specialties only small changes were found. The only specialty with a large increase were neurologists and psychiatrists (27.2% vs. 43.0%). Differences depending on sex and age were rather small while NHR with dementia or a higher care level had lower contact rates after institutionalization. Before institutionalization most patients were referred to a specialist by a general practitioner (61.7-73.9%) while thereafter this proportion decreased substantially (27.8-58.6%). The strongest predictor for a specialist contact after admission to a nursing home was a contact to a specialist before (OR 8.8, CI 7.96-9.72 for contacts to neurologists or psychiatrists). A higher nursing care level and a higher age were also predictors for specialist contacts. CONCLUSIONS: Relevant decreases of ambulatory specialist care utilization after institutionalization are restricted to ophthalmologists. NHR of higher age and higher nursing care level had a lower chance for a specialist contact. The assessment of the adequacy of the provided care after institutionalization remains inconclusive due to little investigated but assumable changes in care needs of NHR. The decreased coordination of care by general practitioners after institutionalization conflicts with health policy goals.


Subject(s)
Nursing Homes/statistics & numerical data , Specialization/statistics & numerical data , Transitional Care , Aged , Aged, 80 and over , Female , Germany , Humans , Insurance Claim Review , Male
20.
BMC Genomics ; 21(1): 588, 2020 Aug 26.
Article in English | MEDLINE | ID: mdl-32842972

ABSTRACT

BACKGROUND: Antagonistic co-evolution can drive rapid adaptation in pathogens and shape genome architecture. Comparative genome analyses of several fungal pathogens revealed highly variable genomes, for many species characterized by specific repeat-rich genome compartments with exceptionally high sequence variability. Dynamic genome structure may enable fast adaptation to host genetics. The wheat pathogen Zymoseptoria tritici with its highly variable genome, has emerged as a model organism to study genome evolution of plant pathogens. Here, we compared genomes of Z. tritici isolates and of sister species infecting wild grasses to address the evolution of genome composition and structure. RESULTS: Using long-read technology, we sequenced and assembled genomes of Z. ardabiliae, Z. brevis, Z. pseudotritici and Z. passerinii, together with two isolates of Z. tritici. We report a high extent of genome collinearity among Zymoseptoria species and high conservation of genomic, transcriptomic and epigenomic signatures of compartmentalization. We identify high gene content variability both within and between species. In addition, such variability is mainly limited to the accessory chromosomes and accessory compartments. Despite strong host specificity and non-overlapping host-range between species, predicted effectors are mainly shared among Zymoseptoria species, yet exhibiting a high level of presence-absence polymorphism within Z. tritici. Using in planta transcriptomic data from Z. tritici, we suggest different roles for the shared orthologs and for the accessory genes during infection of their hosts. CONCLUSION: Despite previous reports of high genomic plasticity in Z. tritici, we describe here a high level of conservation in genomic, epigenomic and transcriptomic composition and structure across the genus Zymoseptoria. The compartmentalized genome allows the maintenance of a functional core genome co-occurring with a highly variable accessory genome.


Subject(s)
Ascomycota , Plant Diseases , Ascomycota/genetics , Genome, Fungal , Prednisolone
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