274 research outputs found

    Circulating miRNAs as Potential Biomarkers for Patient Stratification in Bipolar Disorder:A Combined Review and Data Mining Approach

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    Bipolar disorder is a debilitating psychiatric condition that is shaped in a concerted interplay between hereditary and triggering risk factors. Profound depression and mania define the disorder, but high clinical heterogeneity among patients complicates diagnosis as well as pharmacological intervention. Identification of peripheral biomarkers that capture the genomic response to the exposome may thus progress the development of personalized treatment. MicroRNAs (miRNAs) play a prominent role in of post-transcriptional gene regulation in the context of brain development and mental health. They are coordinately modulated by multifarious effectors, and alteration in their expression profile has been reported in a variety of psychiatric conditions. Intriguingly, miRNAs can be released from CNS cells and enter circulatory bio-fluids where they remain remarkably stable. Hence, peripheral circulatory miRNAs may act as bio-indicators for the combination of genetic risk, environmental exposure, and/or treatment response. Here we provide a comprehensive literature search and data mining approach that summarize current experimental evidence supporting the applicability of miRNAs for patient stratification in bipolar disorder

    “Candidatus Dechloromonas phosphoritropha” and “Ca. D. phosphorivorans”, novel polyphosphate accumulating organisms abundant in wastewater treatment systems

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    Members of the genus Dechloromonas are often abundant in enhanced biological phosphorus removal (EBPR) systems and are recognized putative polyphosphate accumulating organisms (PAOs), but their role in phosphate removal is still unclear. Here, we used 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH) to investigate the abundance and distribution of Dechloromonas spp. in Danish and global wastewater treatment plants. The two most abundant species worldwide revealed in situ dynamics of important intracellular storage polymers, measured by FISH-Raman in activated sludge from four full-scale EBPR plants and from a lab-scale reactor fed with different substrates. Moreover, seven distinct Dechloromonas species were determined from a set of ten high-quality metagenome-assembled genomes (MAGs) from Danish EBPR plants, each encoding the potential for polyphosphate (poly-P), glycogen, and polyhydroxyalkanoates (PHA) accumulation. The two species exhibited an in situ phenotype in complete accordance with the metabolic information retrieved by the MAGs, with dynamic levels of poly-P, glycogen, and PHA during feast-famine anaerobic–aerobic cycling, legitimately placing these microorganisms among the important PAOs. They are potentially involved in denitrification showing niche partitioning within the genus and with other important PAOs. As no isolates are available for the two species, we propose the names Candidatus Dechloromonas phosphoritropha and Candidatus Dechloromonas phosphorivorans

    Low Global Diversity of Candidatus Microthrix, a Troublesome Filamentous Organism in Full-Scale WWTPs

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    Candidatus Microthrix is one of the most common bulking filamentous microorganisms found in activated sludge wastewater treatment plants (WWTPs) across the globe. One species, Ca. M. parvicella, is frequently observed, but global genus diversity, as well as important aspects of its ecology and physiology, are still unknown. Here, we use the MiDAS ecosystem-specific 16S rRNA gene database in combination with amplicon sequencing of Danish and global WWTPs to investigate Ca. Microthrix spp. diversity, distribution, and factors affecting their global presence. Only two species were abundant across the world confirming low diversity of the genus: the dominant Ca. M. parvicella and an unknown species typically present along with Ca. M. parvicella, although usually in lower abundances. Both species were mostly found in Europe at low-to-moderate temperatures and their growth was favored in municipal WWTPs with advanced process designs. As no isolate is available for the novel species, we propose the name “Candidatus Microthrix subdominans.” Ten high-quality metagenome-assembled genomes recovered from Danish WWTPs, including 6 representing the novel Ca. M. subdominans, demonstrated high genetic similarity between the two species with a likely preference for lipids, a putative capability to reduce nitrate and nitrite, and the potential to store lipids and poly-P. Ca. M. subdominans had a potentially more versatile metabolism including additional sugar transporters, higher oxygen tolerance, and the potential to use carbon monoxide as energy source. Newly designed fluorescence in situ hybridization probes revealed similar filamentous morphology for both species. Raman microspectroscopy was used to quantify the in situ levels of intracellular poly-P. Despite the observed similarities in their physiology (both by genomes and in situ), the two species showed different seasonal dynamics in Danish WWTPs through a 13-years survey, possibly indicating occupation of slightly different niches. The genomic information provides the basis for future research into in situ gene expression and regulation, while the new FISH probes provide a useful tool for further characterization in situ. This study is an important step toward understanding the ecology of Ca. Microthrix in WWTPs, which may eventually lead to optimization of control strategies for its growth in this ecosystem

    Effectiveness of accelerated perioperative care and rehabilitation intervention compared to current intervention after hip and knee arthroplasty. A before-after trial of 247 patients with a 3-month follow-up

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    <p>Abstract</p> <p>Background</p> <p>In Denmark, approximately 12,000 hip and knee arthroplasties were performed in 2006, and the hospital costs were close to US$ 110,000,000. In a randomized clinical trial, we have recently demonstrated the efficacy of accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty compared to current intervention under ideal circumstances. We do not, however, know whether these results could be reached under usual circumstances of healthcare practice. We therefore investigated whether length of stay after implementation of accelerated perioperative care and rehabilitation after hip and knee arthroplasty could be reduced in a normal healthcare setting, and how the achieved results matched those observed during the randomized clinical trial.</p> <p>Methods</p> <p>An effectiveness study as a before-after trial was undertaken in which all elective primary total hip and total knee arthroplasty patients were divided into a before-implementation group receiving the current perioperative procedure, and an after-implementation group receiving the new accelerated perioperative care and rehabilitation procedures as provided by a new multi-disciplinary organization. We used the Breakthrough Series Collaborative Model for implementation. The primary outcome measure was in hospital length of stay (LOS), and the secondary outcome measure was adverse effects within 3 months postoperatively.</p> <p>Results</p> <p>We included a total of 247 patients. Mean LOS was significantly (<it>P </it>< 0.001) reduced by 4.4 (95% CI 3.8–5.0) days after implementation of the accelerated intervention, from 8.8 (SD 3.0) days before implementation to 4.3 (SD 1.8) days after implementation. No significant differences in adverse effects were observed. LOS in this effectiveness study was significantly lower than LOS reported in the efficacy study.</p> <p>Conclusion</p> <p>Accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty was successfully and effectively implemented. Results obtained during usual hospital circumstances matched the results achieved under ideal circumstances in this group of patients.</p

    Contribution of income and job strain to the association between education and cardiovascular disease in 1.6 million Danish employees

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    Aims We examined the extent to which associations between education and cardiovascular disease (CVD) morbidity and mortality are attributable to income and work stress. Methods and results We included all employed Danish residents aged 30-59 years in 2000. Cardiovascular disease morbidity analyses included 1 638 270 individuals, free of cardiometabolic disease (CVD or diabetes). Mortality analyses included 41 944 individuals with cardiometabolic disease. We assessed education and income annually from population registers and work stress, defined as job strain, with a job-exposure matrix. Outcomes were ascertained until 2014 from health registers and risk was estimated using Cox regression. During 10 957 399 (men) and 10 776 516 person-years (women), we identified 51 585 and 24 075 incident CVD cases, respectively. For men with low education, risk of CVD was 1.62 [95% confidence interval (CI) 1.58-1.66] before and 1.46 (95% CI 1.42-1.50) after adjustment for income and job strain (25% reduction). In women, estimates were 1.66 (95% CI 1.61-1.72) and 1.53 (95% CI 1.47-1.58) (21% reduction). Of individuals with cardiometabolic disease, 1736 men (362 234 personyears) and 341 women (179 402 person-years) died from CVD. Education predicted CVD mortality in both sexes. Estimates were reduced with 54% (men) and 33% (women) after adjustment for income and job strain. Conclusion Low education predicted incident CVD in initially healthy individuals and CVD mortality in individuals with prevalent cardiometabolic disease. In men with cardiometabolic disease, income and job strain explained half of the higher CVD mortality in the tow education group. In healthy men and in women regardless of cardiometabolic disease, these factors explained 21-33% of the higher CVD morbidity and mortality.Peer reviewe

    What causes treatment failure - the patient, primary care, secondary care or inadequate interaction in the health services?

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    <p>Abstract</p> <p>Background</p> <p>Optimal treatment gives complete relief of symptoms of many disorders. But even if such treatment is available, some patients have persisting complaints. One disorder, from which the patients should achieve complete relief of symptoms with medical or surgical treatment, is gastroesophageal reflux disease (GERD). Despite the fact that such treatment is cheap, safe and easily available; some patients have persistent complaints after contact with the health services. This study evaluates the causes of treatment failure.</p> <p>Methods</p> <p>Twelve patients with GERD and persistent complaints had a semi-structured interview which focused on the patients' evaluation of treatment failure. The interviews were taped, transcribed and evaluated by 18 physicians, (six general practitioners, six gastroenterologists and six gastrointestinal surgeons) who completed a questionnaire for each patient. The questionnaires were scored, and the relative responsibility for the failure was attributed to the patient, primary care, secondary care and interaction in the health services.</p> <p>Results</p> <p>Failing interaction in the health services was the most important cause of treatment failure, followed by failure in primary care, secondary care and the patient himself; the relative responsibilities were 35%, 28%, 27% and 10% respectively. There was satisfactory agreement about the causes between doctors with different specialities, but significant inter-individual differences between the doctors. The causes of the failures differed between the patients.</p> <p>Conclusions</p> <p>Treatment failure is a complex problem. Inadequate interaction in the health services seems to be important. Improved communication between parts of the health services and with the patients are areas of improvement.</p
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