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1.
Proc Natl Acad Sci U S A ; 119(41): e2122042119, 2022 10 11.
Article in English | MEDLINE | ID: mdl-36191216

ABSTRACT

The microfossil record demonstrates the presence of eukaryotic organisms in the marine ecosystem by about 1,700 million years ago (Ma). Despite this, steranes, a biomarker indicator of eukaryotic organisms, do not appear in the rock record until about 780 Ma in what is known as the "rise of algae." Before this, it is argued that eukaryotes were minor ecosystem members, with prokaryotes dominating both primary production and ecosystem dynamics. In this view, the rise of algae was possibly sparked by increased nutrient availability supplying the higher nutrient requirements of eukaryotic algae. Here, we challenge this view. We use a size-based ecosystem model to show that the size distribution of preserved eukaryotic microfossils from 1,700 Ma and onward required an active eukaryote ecosystem complete with phototrophy, osmotrophy, phagotrophy, and mixotrophy. Model results suggest that eukaryotes accounted for one-half or more of the living biomass, with eukaryotic algae contributing to about one-half of total marine primary production. These ecosystems lived with deep-water phosphate levels of at least 10% of modern levels. The general lack of steranes in the pre-780-Ma rock record could be a result of poor preservation.


Subject(s)
Ecosystem , Eukaryota , Biomarkers , Fossils , Phosphates , Water
2.
Prev Vet Med ; 203: 105621, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35344801

ABSTRACT

Clinical presentations of umbilical outpouchings (UOs) in pigs cover a variety of pathological manifestations. Pigs with UOs often do not reach the abattoir as they die due to complications or are euthanized for welfare concerns. The primary objective was to characterize the gross appearance of UOs in pigs with respect to the different types of pathological manifestations. Also the association between the pathological manifestation and presence of a wound on the UO was evaluated. Pigs (in different age groups, n = 444) with an UO were sampled in Denmark from different locations (two herds and at an abattoir) and examined post mortem. Tissue samples from animals with an enterocystoma or internal umbilical proliferations were collected for histological and immunohistochemical characterization. Hernia umbilicalis was the most frequent cause (72%, n = 320) of the UOs. It was the only diagnosis in 57% (n = 254) of the pigs, and in 15% (n = 66) of the pigs the hernia appeared in combination with other manifestations. Thus, 28% (n = 124) of the pigs were diagnosed with an enterocystoma, internal umbilical proliferations, subcutaneous abscess/ fibrosis or another diagnosis, presented alone or in combination. The distribution of diagnoses varied in the different age groups. Overall, 38% (110/291) of the pigs presented a wound on the UOs post mortem. The age of the pigs confounded the relation between the pathological manifestation and the presence of a wound. The odds that an UO had a wound were lower among pigs with a subcutaneous abscess/ fibrosis compared to pigs diagnosed with an umbilical hernia or enterocystoma (OR, 0.3; 95% Cl, 0.1-0.7). The odds of wounds were higher among weaners (OR, 4.3; 95% Cl 2.3-8.3) and finishers (OR, 6.5; 95% Cl, 3.4-12.7) compared with piglets from the farrowing unit. The area of wounds ranged from 0.03 to 78.5 cm2 and increased with age (P < 0.001). Histologically and immunohistochemically the enterocystomas and internal umbilical proliferations seemed to be lined with mesothelial cells and both had a content comparable with mesenchymal embryonic connective tissue. However, only the cavities of the enterocystomas were also lined with mesothelial cells. In conclusion, UOs in pigs are caused by complex pathological conditions with hernia umbilicalis as the dominating diagnosis. Knowledge clarifying the different pathological manifestations causing an UO and the presence of wounds on the UOs is essential for future prevention strategies.


Subject(s)
Hernia, Umbilical , Swine Diseases , Abattoirs , Abscess/veterinary , Animals , Euthanasia, Animal , Fibrosis , Hernia, Umbilical/veterinary , Swine , Swine Diseases/epidemiology
3.
Prev Vet Med ; 191: 105343, 2021 Apr 10.
Article in English | MEDLINE | ID: mdl-33887619

ABSTRACT

Umbilical hernia and other conditions clinically evident as umbilical outpouchings (UOs) affect the welfare and economy in Danish pig production. The objectives of the current study were to characterize the associations between 1) time of detection of the UOs and the odds of dying before scheduled slaughter; 2) time of death, irrespective of the cause, and clinical signs of the UOs, i.e. general condition, size, reducibility, form and skin-color of the UOs; and 3) occurrence of wounds on the UOs and clinical signs: general condition, size, reducibility, form and skin-color. A cohort of Danish conventional pigs with UOs (n = 255) were followed from the detection of an UO until spontaneous death, euthanization or slaughter of the pig. The pigs were clinically examined once a month, and when pigs with an UO died spontaneously, were euthanized or slaughtered, the causes and date of death were recorded. The effects of the clinical manifestations on overall survival were assessed using a Cox proportional hazards model. In total 57 % of the pigs died spontaneously or were euthanized before slaughter. The median age of spontaneous death or euthanasia was 85 days. The UOs were detected at different ages, with half of the pigs (52 %) detected in the farrowing section. No significant association was found between death before scheduled slaughter and the time of detection. Three different clinical manifestations were found to have a prognostic value for overall survival until slaughter, i.e. skin-color of the UO, a general condition of the pig and the size of the UO. An interaction was present between the size and the skin-color of the UO. Wounds on the UO were the most frequent complication resulting in euthanasia (37 %). The odds for developing a wound on the UO were higher for pigs in a general bad condition compared to pigs in a good condition (OR, 5.4; 95 % CL 2.5-11.3), and for pigs with an UO large in size compared to pigs with a small UO (OR, 4.8; 95 % CL 3.0-7.5). The identification of prognostic clinical signs in pigs with an UO is useful in the assessment and decision-making in relation to the future prospects of pigs with UOs.

4.
Res Pract Thromb Haemost ; 4(8): 1324-1330, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33313471

ABSTRACT

BACKGROUND: Hemophilia A is an X chromosome-linked bleeding disorder caused by the deficiency of coagulation factor VIII (FVIII). The majority of the Indian population with hemophilia A use plasma-derived clotting factors and, in some instances, fresh frozen plasma and cryoprecipitate. Safer and more efficient treatment options are needed for this group of patients. OBJECTIVES: To assess the safety of turoctocog alfa, a third-generation recombinant FVIII molecule, for the treatment and prophylaxis of bleeding episodes in previously treated Indian patients with moderate or severe hemophilia A. PATIENTS/METHODS: This single-country, multicenter, open-label, nonrandomized trial enrolled 60 patients who received prophylactic treatment with turoctocog alfa for 8 weeks, which corresponded to a minimum of 20 exposure days. Confirmed development of FVIII inhibitors during the 8-week treatment period was evaluated. Other assessments included frequencies of adverse drug reactions (ARs), serious adverse reactions, drug-related allergic reactions, and infusion reactions during the 12-week period after the first treatment; hemostatic effect of turoctocog alfa for the treatment of bleeding episodes; and total annualized dose of turoctocog alfa administered during the 8-week treatment period. RESULTS: No incidence of FVIII inhibitors was detected. No safety concerns such as ARs, serious ARs, or drug-related allergic reactions were noted. The hemostatic success rate for the treatment of bleeding episodes with turoctocog alfa was 81.6%. CONCLUSIONS: The trial results demonstrated that turoctocog alfa is a safe treatment option for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with hemophilia A in the Indian population.

5.
Virulence ; 4(8): 671-85, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24005110

ABSTRACT

Bacillus anthracis, the causative agent of anthrax, is a zoonotic pathogen that is relatively common throughout the world and may cause life threatening diseases in animals and humans. There are many PCR-based assays in use for the detection of B. anthracis. While most of the developed assays rely on unique markers present on virulence plasmids pXO1 and pXO2, relatively few assays incorporate chromosomal DNA markers due to the close relatedness of B. anthracis to the B. cereus group strains. For the detection of chromosomal DNA, different genes have been used, such as BA813, rpoB, gyrA, plcR, S-layer, and prophage-lambda. Following a review of the literature, an in silico analysis of all signature sequences reported for identification of B. anthracis was conducted. Published primer and probe sequences were compared for specificity against 134 available Bacillus spp. genomes. Although many of the chromosomal targets evaluated are claimed to be specific to B. anthracis, cross-reactions with closely related B. cereus and B. thuringiensis strains were often observed. Of the 35 investigated PCR assays, only 4 were 100% specific for the B. anthracis chromosome. An interlaboratory ring trial among five European laboratories was then performed to evaluate six assays, including the WHO recommended procedures, using a collection of 90 Bacillus strains. Three assays performed adequately, yielding no false positive or negative results. All three assays target chromosomal markers located within the lambdaBa03 prophage region (PL3, BA5345, and BA5357). Detection limit was further assessed for one of these highly specific assays.


Subject(s)
Anthrax/diagnosis , Bacillus anthracis/genetics , Bacillus anthracis/isolation & purification , Computational Biology , Molecular Diagnostic Techniques/methods , Polymerase Chain Reaction/methods , Animals , Bacillus cereus/genetics , Bacillus thuringiensis/genetics , Chromosomes, Bacterial , DNA Primers/genetics , DNA, Bacterial/genetics , Humans , Sensitivity and Specificity
6.
Biosecur Bioterror ; 11 Suppl 1: S146-57, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971800

ABSTRACT

In the field of diagnostic microbiology, rapid molecular methods are critically important for detecting pathogens. With rapid and accurate detection, preventive measures can be put in place early, thereby preventing loss of life and further spread of a disease. From a preparedness perspective, early detection and response are important in order to minimize the consequences. During the past 2 decades, advances in next-generation sequencing (NGS) technology have changed the playing field of molecular methods. Today, it is within reach to completely sequence the total microbiological content of a clinical sample, creating a metagenome, in a single week of laboratory work. As new technologies emerge, their dissemination and capacity building must be facilitated, and criteria for use, as well as guidelines on how to report results, must be established. This article focuses on the use of metagenomics, from sample collection to data analysis and to some extent NGS, for the detection of pathogens, the integration of the technique in outbreak response systems, and the risk-based evaluation of sample processing in routine diagnostics labs. The article covers recent advances in the field, current debate, gaps in research, and future directions. Examples of metagenomic detection, as well as possible applications of the methods, are described in various biopreparedness outbreak scenarios.


Subject(s)
Animal Diseases/epidemiology , Animal Diseases/microbiology , Bioterrorism , Disease Outbreaks , Metagenomics/methods , Analytic Sample Preparation Methods , Animals , Capacity Building , Civil Defense , Computational Biology , Humans , Sequence Analysis, DNA
7.
Biosecur Bioterror ; 11 Suppl 1: S158-65, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971801

ABSTRACT

Deliberate or accidental contamination of food, feed, and water supplies poses a threat to human health worldwide. A rapid and sensitive detection technique that could replace the current labor-intensive and time-consuming culture-based methods is highly desirable. In addition to species-specific assays, such as PCR, there is a need for generic methods to screen for unknown pathogenic microorganisms in samples. This work presents a metagenomics-based direct-sequencing approach for detecting unknown microorganisms, using Bacillus cereus (as a model organism for B. anthracis) in bottled water as an example. Total DNA extraction and 16S rDNA gene sequencing were used in combination with principle component analysis and multicurve resolution to study detection level and possibility for identification. Results showed a detection level of 10(5) to 10(6) CFU/L. Using this method, it was possible to separate 2 B. cereus strains by the principal component plot, despite the close sequence resemblance. A linear correlation between the artificial contamination level and the relative amount of the Bacillus artificial contaminant in the metagenome was observed, and a relative amount value above 0.5 confirmed the presence of Bacillus. The analysis also revealed that background flora in the bottled water varied between the different water types that were included in the study. This method has the potential to be adapted to other biological matrices and bacterial pathogens for fast screening of unknown bacterial threats in outbreak situations.


Subject(s)
Bacillus cereus/genetics , Bacillus cereus/isolation & purification , DNA, Ribosomal/analysis , Drinking Water/microbiology , Metagenomics/methods , Bioterrorism , Gene Amplification , Humans , Polymerase Chain Reaction , Principal Component Analysis , Sequence Analysis, DNA/methods
8.
Biosecur Bioterror ; 11 Suppl 1: S177-82, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971804

ABSTRACT

Botulism disease in both humans and animals is a worldwide concern. Botulinum neurotoxins produced by Clostridium botulinum and other Clostridium species are the most potent biological substances known and are responsible for flaccid paralysis leading to a high mortality rate. Clostridium botulinum and botulinum neurotoxins are considered potential weapons for bioterrorism and have been included in the Australia Group List of Biological Agents. In 2010 the European Commission (DG Justice, Freedom and Security) funded a 3-year project named AniBioThreat to improve the EU's capacity to counter animal bioterrorism threats. A detection portfolio with screening methods for botulism agents and incidents was needed to improve tracking and tracing of accidental and deliberate contamination of the feed and food chain with botulinum neurotoxins and other Clostridia. The complexity of this threat required acquiring new genetic information to better understand the diversity of these Clostridia and develop detection methods targeting both highly specific genetic markers of these Clostridia and the neurotoxins they are able to produce. Several European institutes participating in the AniBioThreat project collaborated on this program to achieve these objectives. Their scientific developments are discussed here.


Subject(s)
Animal Diseases/diagnosis , Animal Diseases/microbiology , Bioterrorism/prevention & control , Botulism/veterinary , Clostridium botulinum/genetics , Agriculture , Animal Feed/microbiology , Animals , Botulinum Toxins/analysis , Botulinum Toxins/genetics , Botulism/diagnosis , Botulism/microbiology , Clostridium botulinum/isolation & purification , DNA Fingerprinting , Endopeptidases , Food Chain , Mass Spectrometry , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA
9.
Biosecur Bioterror ; 11 Suppl 1: S183-90, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971805

ABSTRACT

A workshop on animal botulism was held in Uppsala, Sweden, in June 2012. Its purpose was to explore the current status of the disease in Europe by gathering the European experts in animal botulism and to raise awareness of the disease among veterinarians and others involved in biopreparedness. Animal botulism is underreported and underdiagnosed, but an increasing number of reports, as well as the information gathered from this workshop, show that it is an emerging problem in Europe. The workshop was divided into 4 sessions: animal botulism in Europe, the bacteria behind the disease, detection and diagnostics, and European collaboration and surveillance. An electronic survey was conducted before the workshop to identify the 3 most needed discussion points, which were: prevention, preparedness and outbreak response; detection and diagnostics; and European collaboration and surveillance. The main conclusions drawn from these discussions were that there is an urgent need to replace the mouse bioassay for botulinum toxin detection with an in vitro test and that there is a need for a European network to function as a reference laboratory, which could also organize a European supply of botulinum antitoxin and vaccines. The foundation of such a network was discussed, and the proposals are presented here along with the outcome of discussions and a summary of the workshop itself.


Subject(s)
Animal Diseases/diagnosis , Animal Diseases/microbiology , Botulism/veterinary , Animal Diseases/prevention & control , Animals , Botulism/diagnosis , Botulism/microbiology , Botulism/prevention & control , Europe , International Cooperation
10.
Biosecur Bioterror ; 11 Suppl 1: S191-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971806

ABSTRACT

Botulism is a severe neuroparalytic disease that affects humans, all warm-blooded animals, and some fishes. The disease is caused by exposure to toxins produced by Clostridium botulinum and other botulinum toxin-producing clostridia. Botulism in animals represents a severe environmental and economic concern because of its high mortality rate. Moreover, meat or other products from affected animals entering the food chain may result in a public health problem. To this end, early diagnosis is crucial to define and apply appropriate veterinary public health measures. Clinical diagnosis is based on clinical findings eliminating other causes of neuromuscular disorders and on the absence of internal lesions observed during postmortem examination. Since clinical signs alone are often insufficient to make a definitive diagnosis, laboratory confirmation is required. Botulinum antitoxin administration and supportive therapies are used to treat sick animals. Once the diagnosis has been made, euthanasia is frequently advisable. Vaccine administration is subject to health authorities' permission, and it is restricted to a small number of animal species. Several measures can be adopted to prevent or minimize outbreaks. In this article we outline all phases of management of animal botulism outbreaks occurring in wet wild birds, poultry, cattle, horses, and fur farm animals.


Subject(s)
Animal Diseases/diagnosis , Animal Diseases/therapy , Botulism/veterinary , Vaccination , Animal Diseases/prevention & control , Animals , Botulinum Toxins , Botulism/diagnosis , Botulism/prevention & control , Botulism/therapy , Cattle , Clostridium botulinum , Horses , Poultry
11.
Anaerobe ; 22: 31-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23669132

ABSTRACT

Two real-time PCR arrays based on the GeneDisc(®) cycler platform (Pall-GeneDisc Technologies) were evaluated in a multicenter collaborative trial for their capacity to specifically detect and discriminate Clostridium botulinum types C, D and their mosaic variants C-D and D-C that are associated with avian and mammalian botulism. The GeneDisc(®) arrays developed as part of the DG Home funded European project 'AnibioThreat' were highly sensitive and specific when tested on pure isolates and naturally contaminated samples (mostly clinical specimen from avian origin). Results of the multicenter collaborative trial involving eight laboratories in five European Countries (two laboratories in France, Italy and The Netherlands, one laboratory in Denmark and Sweden), using DNA extracts issued from 33 pure isolates and 48 naturally contaminated samples associated with animal botulism cases, demonstrated the robustness of these tests. Results showed a concordance among the eight laboratories of 99.4%-100% for both arrays. The reproducibility of the tests was high with a relative standard deviation ranging from 1.1% to 7.1%. Considering the high level of agreement achieved between the laboratories these PCR arrays constitute robust and suitable tools for rapid detection of C. botulinum types C, D and mosaic types C-D and D-C. These are the first tests for C. botulinum C and D that have been evaluated in a European multicenter collaborative trial.


Subject(s)
Botulism/diagnosis , Botulism/microbiology , Clostridium botulinum type C/classification , Clostridium botulinum type C/genetics , Clostridium botulinum type D/classification , Clostridium botulinum type D/genetics , Real-Time Polymerase Chain Reaction/methods , Animals , Clostridium botulinum type C/isolation & purification , Clostridium botulinum type D/isolation & purification , Europe , Humans , Reproducibility of Results
12.
PLoS One ; 7(12): e51196, 2012.
Article in English | MEDLINE | ID: mdl-23236453

ABSTRACT

We investigated if the transcriptional response of Salmonella Typhimurium to temperature and acid variations was hysteretic, i.e. whether the transcriptional regulation caused by environmental stimuli showed memory and remained after the stimuli ceased. The transcriptional activity of non-replicating stationary phase cells of S. Typhimurium caused by the exposure to 45 °C and to pH 5 for 30 min was monitored by microarray hybridizations at the end of the treatment period as well as immediately and 30 minutes after conditions were set back to their initial values, 25 °C and pH 7. One hundred and two out of 120 up-regulated genes during the heat shock remained up-regulated 30 minutes after the temperature was set back to 25 °C, while only 86 out of 293 down regulated genes remained down regulated 30 minutes after the heat shock ceased. Thus, the majority of the induced genes exhibited hysteresis, i.e., they remained up-regulated after the environmental stress ceased. At 25 °C the transcriptional regulation of genes encoding for heat shock proteins was determined by the previous environment. Gene networks constructed with up-regulated genes were significantly more modular than those of down-regulated genes, implying that down-regulation was significantly less synchronized than up-regulation. The hysteretic transcriptional response to heat shock was accompanied by higher resistance to inactivation at 50 °C as well as cross-resistance to inactivation at pH 3; however, growth rates and lag times at 43 °C and at pH 4.5 were not affected. The exposure to pH 5 only caused up-regulation of 12 genes and this response was neither hysteretic nor accompanied of increased resistance to inactivation conditions. Cellular memory at the transcriptional level may represent a mechanism of adaptation to the environment and a deterministic source of variability in gene regulation.


Subject(s)
Antifreeze Proteins/metabolism , Gene Expression Regulation/physiology , Heat-Shock Response/physiology , Salmonella typhimurium/growth & development , Transcription, Genetic/physiology , Analysis of Variance , Hot Temperature , Hydrogen-Ion Concentration , Microarray Analysis , Protein Folding
13.
Ugeskr Laeger ; 174(18): 1234-5, 2012 Apr 30.
Article in Danish | MEDLINE | ID: mdl-22546163

ABSTRACT

An 82 year-old man presented with a unilateral tumour in the right testis. A complete orchiectomy was subsequently performed. Histological examination showed a malign germ cell tumour of yolk sac type. Rete testis invasion was present, but there was no vascular or lymphatic invasion and the tumour did not extend tunica albuginea. Computed tomography of the abdomen caused no suspicion of metastasis and there were no elevated tumour markers postoperative. Yolk sac tumour in the elderly is very uncommon, but the diagnosis is important since it has a different clinical behaviour than juvenile yolk sac tumours.


Subject(s)
Endodermal Sinus Tumor/pathology , Testicular Neoplasms/pathology , Age Factors , Aged, 80 and over , Endodermal Sinus Tumor/surgery , Humans , Male , Orchiectomy , Testicular Neoplasms/surgery
14.
J Mol Biol ; 411(3): 529-36, 2011 Aug 19.
Article in English | MEDLINE | ID: mdl-21723290

ABSTRACT

Complete characterization of a biomolecule's chemical structure is crucial in the full understanding of the relations between their structure and function. The dominating components in ribosomes are ribosomal RNAs (rRNAs), and the entire rRNA-but a single modified nucleoside at position 2501 in 23S rRNA-has previously been characterized in the bacterium Escherichia coli. Despite a first report nearly 20 years ago, the chemical nature of the modification at position 2501 has remained elusive, and attempts to isolate it have so far been unsuccessful. We unambiguously identify this last unknown modification as 5-hydroxycytidine-a novel modification in RNA. Identification of 5-hydroxycytidine was completed by liquid chromatography under nonoxidizing conditions using a graphitized carbon stationary phase in combination with ion trap tandem mass spectrometry and by comparing the fragmentation behavior of the natural nucleoside with that of a chemically synthesized ditto. Furthermore, we show that 5-hydroxycytidine is also present in the equivalent position of 23S rRNA from the bacterium Deinococcus radiodurans. Given the unstable nature of 5-hydroxycytidine, this modification might be found in other RNAs when applying the proper analytical conditions as described here.


Subject(s)
Cytosine/analogs & derivatives , Escherichia coli/genetics , RNA, Ribosomal, 23S/chemistry , RNA, Ribosomal, 23S/genetics , Chromatography, Liquid , Cytosine/chemistry , Deinococcus/genetics , Mass Spectrometry , Models, Chemical , Nucleic Acid Conformation , Nucleotides/genetics , Polymorphism, Single Nucleotide , RNA, Bacterial/chemistry , RNA, Bacterial/genetics , Ribosomes
15.
Disabil Rehabil ; 32(17): 1447-60, 2010.
Article in English | MEDLINE | ID: mdl-20624108

ABSTRACT

AIM: The aim of this study was to describe and define the rehabilitation approach: 'Facial Oral Tract Therapy' (F.O.T.T.). METHOD: We defined the content and process of the rehabilitation approach (F.O.T.T.) in a decision-algorithm supported by a manual with supplementary material. The algorithm was developed by a research occupational therapist and an F.O.T.T. senior instructor. We used an inductive approach combining existing knowledge from: F.O.T.T. instructors, therapists trained in using the F.O.T.T. approach, and existing literature. A group of F.O.T.T. instructors and the originator of the treatment approach Mrs. Kay Coombes has given comments to and approved the algorithm. RESULT: The algorithm consist of five flowcharts: 'one assessment' chart guiding the therapist in the examination of the patient and four 'treatment charts', one for each of the four areas of F.O.T.T.: swallowing and eating; oral hygiene; breathing, voice, and speech articulation; facial expression, giving guidance on interventions. The algorithm outlines all important components in the treatment that the therapist should decide to use or not to use in the intervention. The algorithm is supported by a manual with criteria of when to use which components. CONCLUSION: This algorithm is designed to be a practical guideline to therapists using F.O.T.T. in clinical practice and in educational settings. The use of this algorithm may support standardization of F.O.T.T. and thereby promote and maintain the quality in the treatment. This in turn will facilitate research that addresses F.O.T.T. and outcomes.


Subject(s)
Algorithms , Occupational Therapy/methods , Articulation Disorders/physiopathology , Articulation Disorders/rehabilitation , Deglutition Disorders/physiopathology , Deglutition Disorders/rehabilitation , Eating/physiology , Facial Expression , Goals , Humans , Nervous System Diseases/physiopathology , Nervous System Diseases/rehabilitation , Nonverbal Communication/physiology , Oral Hygiene
16.
RNA ; 16(8): 1584-96, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20558545

ABSTRACT

Cells devote a significant effort toward the production of multiple modified nucleotides in rRNAs, which fine tune the ribosome function. Here, we report that two methyltransferases, RsmB and RsmF, are responsible for all four 5-methylcytidine (m(5)C) modifications in 16S rRNA of Thermus thermophilus. Like Escherichia coli RsmB, T. thermophilus RsmB produces m(5)C967. In contrast to E. coli RsmF, which introduces a single m(5)C1407 modification, T. thermophilus RsmF modifies three positions, generating m(5)C1400 and m(5)C1404 in addition to m(5)C1407. These three residues are clustered near the decoding site of the ribosome, but are situated in distinct structural contexts, suggesting a requirement for flexibility in the RsmF active site that is absent from the E. coli enzyme. Two of these residues, C1400 and C1404, are sufficiently buried in the mature ribosome structure so as to require extensive unfolding of the rRNA to be accessible to RsmF. In vitro, T. thermophilus RsmF methylates C1400, C1404, and C1407 in a 30S subunit substrate, but only C1400 and C1404 when naked 16S rRNA is the substrate. The multispecificity of T. thermophilus RsmF is potentially explained by three crystal structures of the enzyme in a complex with cofactor S-adenosyl-methionine at up to 1.3 A resolution. In addition to confirming the overall structural similarity to E. coli RsmF, these structures also reveal that key segments in the active site are likely to be dynamic in solution, thereby expanding substrate recognition by T. thermophilus RsmF.


Subject(s)
Methyltransferases/chemistry , Methyltransferases/metabolism , RNA, Ribosomal/metabolism , Thermus thermophilus/enzymology , Thermus thermophilus/genetics , Binding Sites/genetics , Cytidine/analogs & derivatives , Escherichia coli/enzymology , Escherichia coli/genetics , Escherichia coli/metabolism , Methyltransferases/genetics , Nucleotides/chemistry , Nucleotides/genetics , RNA, Ribosomal/genetics , Ribosomes/genetics , Ribosomes/metabolism , Thermus thermophilus/metabolism
17.
Ugeskr Laeger ; 172(2): 120-4, 2010 Jan 11.
Article in Danish | MEDLINE | ID: mdl-20376916

ABSTRACT

An unknown number of asylum seekers arriving in Denmark have been exposed to torture. Amnesty International's Danish Medical Group examined 142 asylum seekers, of whom 45% had been exposed to torture. Physical and psychological symptoms were 2-3 times as frequent among torture survivors as among non-tortured asylum seekers. Among the torture survivors, 63% fulfilled the criteria of post-traumatic stress disorder, 58% had objective psychological findings, and 42% had torture-related scars. Identification of torture survivors is important in order to initiate the necessary medical treatment.


Subject(s)
Health Status , Mental Disorders/epidemiology , Refugees/psychology , Stress Disorders, Post-Traumatic/epidemiology , Wounds and Injuries/epidemiology , Adolescent , Adult , Aged , Denmark/epidemiology , Denmark/ethnology , Female , Health Surveys , Humans , International Cooperation , Male , Mental Disorders/diagnosis , Middle Aged , Stress Disorders, Post-Traumatic/diagnosis , Torture/psychology , Torture/statistics & numerical data , Violence/psychology , Violence/statistics & numerical data , Wounds and Injuries/diagnosis , Young Adult
18.
Scand J Gastroenterol ; 45(4): 477-82, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19968612

ABSTRACT

OBJECTIVE: The value of repeating endoscopic ultrasound (EUS) is seldom described. This study evaluates a patient population in which EUS was repeated. MATERIAL AND METHODS: This was a retrospective study of patients who between January 2002 and December 2006 had an EUS scan performed; this EUS scan (re-EUS) was the second or more EUS scan performed. RESULTS: Over the study period, the department performed 3024 EUS procedures, of which 561 investigations were defined as re-EUS. According to defined exclusion criteria, 244 procedures were not analyzed further. The study group thus consisted of 317 procedures (242 patients). In 163 cases (126 patients), re-EUS was planned by the endosonographer for control of an undetermined lesion. The first re-EUS scan performed changed the further management in 91 of 126 patients (72%). Sensitivity and specificity of re-EUS regarding pancreatic cancer were 0.65 and 1.00, respectively. Re-EUS was performed in 82 cases (77 patients) where no re-investigation had been planned at the initial EUS scan but worsening of symptoms or new findings of other imaging procedures had led to an additional EUS scan. Thirteen of these patients (17%) proved to have pancreatic cancer. In 62 cases (57 patients) re-EUS and EUS-guided fine-needle aspiration (FNA) had been planed in order to confirm the suspicion of malignant disease. Following re-EUS and EUS-FNA, 40 of these patients could be referred for either oncology or surgery. In the remaining 10 cases, re-EUS was performed for miscellaneous indications. CONCLUSION: Re-EUS has a substantial clinical impact on the further management of the patient.


Subject(s)
Endosonography/methods , Gastrointestinal Neoplasms/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Child , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/diagnostic imaging , Retreatment , Retrospective Studies , Sensitivity and Specificity
19.
Cancer Chemother Pharmacol ; 66(2): 295-301, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19882157

ABSTRACT

PURPOSE: We assessed the efficacy and toxicity of a fixed dose of docetaxel and prednisone, combined with escalating doses of gemcitabine (DGP). The primary endpoint was PSA response. METHODS: Fifteen patients were enrolled in the phase I and 50 patients entered the phase II. Patients were given DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC), adequate function of liver, kidney and bone marrow; ECOG performance status

Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Orchiectomy , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Anti-Inflammatory Agents/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Docetaxel , Endpoint Determination , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Pain/epidemiology , Pain/etiology , Palliative Care , Prednisone/administration & dosage , Prostatic Neoplasms/pathology , Survival Analysis , Taxoids/administration & dosage , Gemcitabine
20.
Arch Phys Med Rehabil ; 89(11): 2114-20, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18996240

ABSTRACT

OBJECTIVES: To investigate the incidence and onset time of pneumonia for patients with severe traumatic brain injury (TBI) in the early phase of rehabilitation and to identify parameters associated with the risk of pneumonia. DESIGN: Observational retrospective cohort study. SETTING: Subacute rehabilitation department in a university hospital in Denmark. PARTICIPANTS: Patients (N=173) aged 16 to 65 years with severe TBI who were admitted during a 5-year period. Patients are transferred to the brain injury unit as soon as they ventilate spontaneously. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Pneumonia. RESULTS: Twenty-seven percent of the patients admitted to the brain injury unit were in treatment for pneumonia; pneumonia developed in 12% of the patients during rehabilitation; the condition occurred within 19 days of admission in all but 1 patient. Of these patients, 81% received nothing by mouth. Three factors identified patients at highest risk of pneumonia: Glasgow Coma Scale score less than 9 (1 day after cessation of sedation); Rancho Los Amigos Scale score less than 3 (on admission); and no oral intake on admission. Having a tracheotomy tube and/or feeding tube was also associated with a higher occurrence of pneumonia. CONCLUSIONS: Among patients with severe TBI, 27% had pneumonia at transfer from the intensive care unit. Pneumonia developed in only 12% of the participants during rehabilitation. Patients with a low level of consciousness and patients with a tracheotomy tube or feeding tube had a higher likelihood of pneumonia.


Subject(s)
Brain Injuries/rehabilitation , Deglutition Disorders/complications , Pneumonia/etiology , Adolescent , Adult , Aged , Brain Injuries/complications , Denmark/epidemiology , Enteral Nutrition , Humans , Incidence , Kaplan-Meier Estimate , Middle Aged , Pneumonia/epidemiology , Pneumonia/microbiology , Pneumonia/prevention & control , Proportional Hazards Models , Retrospective Studies , Risk Factors , Tracheostomy
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