Open and hidden agendas of "asymptomatic" patients who request check-up exams

BACKGROUND: Current guidelines for a check-up recommend routine screening not triggered by specific symptoms for some known risk factors and diseases in the general population. Patients' perceptions and expectations regarding a check-up exam may differ from these principles. However, quantitative and qualitative data about the discrepancy between patient- and provider expectations for this type of clinic consultation is lacking. METHODS: For a year, we prospectively enrolled 66 patients who explicitly requested a "check-up" at our medical outpatient division. All patients actively denied upon prompting having any symptoms or specific health concerns at the time they made their appointment. All consultations were videotaped and analysed for information about spontaneously mentioned symptoms and reasons for the clinic consultation ("open agendas") and for cues to hidden patient agendas using the Roter interaction analysis system (RIAS). RESULTS: All patients initially declared to be asymptomatic but this was ultimately the case in only 7 out of 66 patients. The remaining 59 patients spontaneously mentioned a mean of 4.2 ± 3.3 symptoms during their first consultation. In 23 patients a total of 31 hidden agendas were revealed. The primary categories for hidden agendas were health concerns, psychosocial concerns and the patient's concept of disease. CONCLUSIONS: The majority of patients requesting a general check-up tend to be motivated by specific symptoms and health concerns and are not "asymptomatic" patients who primarily come for preventive issues. Furthermore, physicians must be alert for possible hidden agendas, as one in three patients have one or more hidden reasons for requesting a check-up

Impella versus extracorporal life support in cardiogenic shock: a propensity score adjusted analysis

Aims: The mortality in cardiogenic shock (CS) is high. The role of specific mechanical circulatory support (MCS) systems is unclear. We aimed to compare patients receiving Impella versus ECLS (extracorporal life support) with regard to baseline characteristics, feasibility, and outcomes in CS. Methods and results: This is a retrospective cohort study including CS patients over 18 years with a complete follow-up of the primary endpoint and available baseline lactate level, receiving haemodynamic support either by Impella 2.5 or ECLS from two European registries. The decision for device implementation was made at the discretion of the treating physician. The primary endpoint of this study was all-cause mortality at 30 days. A propensity score for the use of Impella was calculated, and multivariable logistic regression was used to obtain adjusted odds ratios (aOR). In total, 149 patients were included, receiving either Impella (n = 73) or ECLS (n = 76) for CS. The feasibility of device implantation was high (87%) and similar (aOR: 3.14; 95% CI: 0.18–56.50; P = 0.41) with both systems. The rates of vascular injuries (aOR: 0.95; 95% CI: 0.10–3.50; P = 0.56) and bleedings requiring transfusions (aOR: 0.44; 95% CI: 0.09–2.10; P = 0.29) were similar in ECLS patients and Impella patients. The use of Impella or ECLS was not associated with increased odds of mortality (aOR: 4.19; 95% CI: 0.53–33.25; P = 0.17), after correction for propensity score and baseline lactate level. Baseline lactate level was independently associated with increased odds of 30 day mortality (per mmol/L increase; OR: 1.29; 95% CI: 1.14–1.45; P < 0.001). Conclusions: In CS patients, the adjusted mortality rates of both ECLS and Impella were high and similar. The baseline lactate level was a potent predictor of mortality and could play a role in patient selection for therapy in future studies. In patients with profound CS, the type of device is likely to be less important compared with other parameters including non-cardiac and neurological factors

Unmet device reprogramming needs at the end of life among patients with implantable cardioverter defibrillator: A systematic review and meta-analysis

Background: Use of implantable cardioverter defibrillators is increasingly common. As patients approach the end of life, it is appropriate to deactivate the shock function. Aim: To assess the prevalence of implantable cardioverter defibrillator reprogramming to deactivate the shock function at the end of life and the prevalence of advance directives among this population. Design: Following a previously established protocol available in PROSPERO, we performed a narrative synthesis of our findings and used the logit transforma

Global population genomics of the forest pathogen Dothistroma septosporum reveal chromosome duplications in high dothistromin-producing strains

Dothistroma needle blight is one of the most devastating pine tree diseases worldwide. New and emerging epidemics have been frequent over the last 25 years, particularly in the Northern Hemisphere, where they are in part associated with changing weather patterns. One of the main Dothistroma needle blight pathogens, Dothistroma septosporum, has a global distribution but most molecular plant pathology research has been confined to Southern Hemisphere populations that have limited genetic diversity. Extensive genomic and transcriptomic data are available for a D. septosporum reference strain from New Zealand, where an introduced clonal population of the pathogen predominates. Due to the global importance of this pathogen, we determined whether the genome of this reference strain is representative of the species worldwide by sequencing the genomes of 18 strains sampled globally from different pine hosts. Genomic polymorphism shows substantial variation within the species, clustered into two distinct groups of strains with centres of diversity in Central and South America. A reciprocal chromosome translocation uniquely identifies the New Zealand strains. Globally, strains differ in their production of the virulence factor dothistromin, with extremely high production levels in strain ALP3 from Germany. Comparisons with the New Zealand reference revealed that several strains are aneuploids; for example, ALP3 has duplications of three chromosomes. Increased gene copy numbers therefore appear to contribute to increased production of dothistromin, emphasizing that studies of population structure are a necessary adjunct to functional analyses of genetic polymorphisms to identify the molecular basis of virulence in this important forest pathogen.Supplementary Material: Fig. S1 Predicted duplications and deletions in chromosomes 1‐14 for 18 strains of D. septosporum.Fig. S2 Initial evidence for a reciprocal chromosome translocation in the NZE10 genome. (A) Assembled contigs from the SLV genome were aligned with NZE10 reference chromosomes (scaffolds). Two contigs (circled) mapped to both chromosomes 5 and 13 of the NZE10 reference genome. This was found in many of the other genome sequences. (B) Visualisation of reads from the ALP3 genome mapped onto a region of chromosome 13 show a gap, in which mate pairs are mapped to chromosome 5.Fig. S3 A reciprocal translocation involving chromosomes 5 and 13 in the NZE10 genome. (A) The reciprocal translation was centred on an identical sequence (GCGCGGT) found at positions 1459800‐1459806 in NZE10 chromosome 5 and 717926‐717932 in chromosome 13. Chromosomes 5 and 13 are shaded grey and pale blue respectively with ends coloured to distinguish the two arms in each case. Coloured sequences surrounding the breakpoint indicate which arm they are from. (B) In strains from regions other than Australasia, the two long sections of NZE10 chromosomes 5 and 13 are joined to make a 2.2 Mb chromosome and two short sections to make a 1.4 Mb chromosome. Sequences around the common 7 bp sequence are shown for strain ALP3 as an example. (C, D) Pairs of divergently transcribed genes straddle the breakpoints on NZE10 chromosomes 5 (C) and 13 (D). A GC content of about 70% was seen at the breakpoint regions (50 bp sliding window) as shown by the %GC (blue) profiles.Fig. S4 Alignment of pathway regulator AflR from 19 D. septosporum strains. Amino acid changes compared to strain NZE10 are highlighted in blue (these sites are also variant between AflR sequences of D. septosporum , Cladosporium fulvum , Aspergillus parasiticus and Aspergillus nidulans ; (Chettri et al ., 2013)) or in green (at sites conserved between those four species). The Zn2Cys6 zinc binuclear domain is highlighted in pink; the linker sequence thought to determine DNA binding specificity in grey; the acidic glutamine rich motif in yellow and C terminal arginine residues implicated in AflJ binding in red.Fig. S5 Secondary structure predictions for AflR from D. septosporum NZE10 and ALP3. Pairwise alignment predicted by HHpred. The arrow indicates the location of the N349K polymorphism in ALP3.Table S1 Transposable elements in the Dothistroma septosporum genomes.Table S2 Genes deleted in the 18 genomes compared to Dothistroma septosporum NZE10.Table S3 Genes deleted from chromosome 14 and their expression levels in NZE10.Table S4 Single Nucleotide Polymorphisms (SNPs) in dothistromin genes, grouped by dothistromin gene loci.Table S5 Deleted genes on Dothistroma septosporum chromosome 12.Table S6 Gene duplications predicted by CNV (copy number variant) analysis.Table S7 (a) Polymerase Chain Reaction (PCR) primers used for verification of 5:13 translocation (b) Primers used for copy number variant (CNV) verification (quantitative PCR [qPCR]).The Bio‐Protection Research Centre of New Zealand, Scion and Massey University.https://onlinelibrary.wiley.com/journal/13643703pm2020BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Global population genomics of the forest pathogen Dothistroma septosporum

Supplementary Material: Fig. S1 Predicted duplications and deletions in chromosomes 1‐14 for 18 strains of D. septosporum.Fig. S2 Initial evidence for a reciprocal chromosome translocation in the NZE10 genome. (A) Assembled contigs from the SLV genome were aligned with NZE10 reference chromosomes (scaffolds). Two contigs (circled) mapped to both chromosomes 5 and 13 of the NZE10 reference genome. This was found in many of the other genome sequences. (B) Visualisation of reads from the ALP3 genome mapped onto a region of chromosome 13 show a gap, in which mate pairs are mapped to chromosome 5.Fig. S3 A reciprocal translocation involving chromosomes 5 and 13 in the NZE10 genome. (A) The reciprocal translation was centred on an identical sequence (GCGCGGT) found at positions 1459800‐1459806 in NZE10 chromosome 5 and 717926‐717932 in chromosome 13. Chromosomes 5 and 13 are shaded grey and pale blue respectively with ends coloured to distinguish the two arms in each case. Coloured sequences surrounding the breakpoint indicate which arm they are from. (B) In strains from regions other than Australasia, the two long sections of NZE10 chromosomes 5 and 13 are joined to make a 2.2 Mb chromosome and two short sections to make a 1.4 Mb chromosome. Sequences around the common 7 bp sequence are shown for strain ALP3 as an example. (C, D) Pairs of divergently transcribed genes straddle the breakpoints on NZE10 chromosomes 5 (C) and 13 (D). A GC content of about 70% was seen at the breakpoint regions (50 bp sliding window) as shown by the %GC (blue) profiles.Fig. S4 Alignment of pathway regulator AflR from 19 D. septosporum strains. Amino acid changes compared to strain NZE10 are highlighted in blue (these sites are also variant between AflR sequences of D. septosporum , Cladosporium fulvum , Aspergillus parasiticus and Aspergillus nidulans ; (Chettri et al ., 2013)) or in green (at sites conserved between those four species). The Zn2Cys6 zinc binuclear domain is highlighted in pink; the linker sequence thought to determine DNA binding specificity in grey; the acidic glutamine rich motif in yellow and C terminal arginine residues implicated in AflJ binding in red.Fig. S5 Secondary structure predictions for AflR from D. septosporum NZE10 and ALP3. Pairwise alignment predicted by HHpred. The arrow indicates the location of the N349K polymorphism in ALP3.Table S1 Transposable elements in the Dothistroma septosporum genomes.Table S2 Genes deleted in the 18 genomes compared to Dothistroma septosporum NZE10.Table S3 Genes deleted from chromosome 14 and their expression levels in NZE10.Table S4 Single Nucleotide Polymorphisms (SNPs) in dothistromin genes, grouped by dothistromin gene loci.Table S5 Deleted genes on Dothistroma septosporum chromosome 12.Table S6 Gene duplications predicted by CNV (copy number variant) analysis.Table S7 (a) Polymerase Chain Reaction (PCR) primers used for verification of 5:13 translocation (b) Primers used for copy number variant (CNV) verification (quantitative PCR [qPCR]).Dothistroma needle blight is one of the most devastating pine tree diseases worldwide. New and emerging epidemics have been frequent over the last 25 years, particularly in the Northern Hemisphere, where they are in part associated with changing weather patterns. One of the main Dothistroma needle blight pathogens, Dothistroma septosporum, has a global distribution but most molecular plant pathology research has been confined to Southern Hemisphere populations that have limited genetic diversity. Extensive genomic and transcriptomic data are available for a D. septosporum reference strain from New Zealand, where an introduced clonal population of the pathogen predominates. Due to the global importance of this pathogen, we determined whether the genome of this reference strain is representative of the species worldwide by sequencing the genomes of 18 strains sampled globally from different pine hosts. Genomic polymorphism shows substantial variation within the species, clustered into two distinct groups of strains with centres of diversity in Central and South America. A reciprocal chromosome translocation uniquely identifies the New Zealand strains. Globally, strains differ in their production of the virulence factor dothistromin, with extremely high production levels in strain ALP3 from Germany. Comparisons with the New Zealand reference revealed that several strains are aneuploids; for example, ALP3 has duplications of three chromosomes. Increased gene copy numbers therefore appear to contribute to increased production of dothistromin, emphasizing that studies of population structure are a necessary adjunct to functional analyses of genetic polymorphisms to identify the molecular basis of virulence in this important forest pathogen.The Bio‐Protection Research Centre of New Zealand, Scion and Massey University.https://onlinelibrary.wiley.com/journal/13643703pm2020BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Induced prion protein controls immune-activated retroviruses in the mouse spleen

The prion protein (PrP) is crucially involved in transmissible spongiform encephalopathies (TSE), but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP