There is increasing interest in naturally produced colorants, and microalgae represent a bio‐technologically interesting source due to their wide range of colored pigments, including chlorophylls ...(green), carotenoids (red, orange and yellow), and phycobiliproteins (red and blue). However, the concentration of these pigments, under optimal growth conditions, is often too low to make microalgal‐based pigment production economically feasible. In some Chlorophyta (green algae), specific process conditions such as oversaturating light intensities or a high salt concentration induce the overproduction of secondary carotenoids (β‐carotene in Dunaliella salina (Dunal) Teodoresco and astaxanthin in Haematococcus pluvialis (Flotow)). Overproduction of all other pigments (including lutein, fucoxanthin, and phycocyanin) requires modification in gene expression or enzyme activity, most likely combined with the creation of storage space outside of the photosystems. The success of such modification strategies depends on an adequate understanding of the metabolic pathways and the functional roles of all the pigments involved. In this review, the distribution of commercially interesting pigments across the most common microalgal groups, the roles of these pigments in vivo and their biosynthesis routes are reviewed, and constraints and opportunities for overproduction of both primary and secondary pigments are presented.
The evidence for the treatment of acceptably reduced intra-articular distal radial fractures remains inconclusive. We therefore compared the functional outcomes of cast immobilization (nonoperative) ...and volar plate fixation (operative) for patients with these fractures.
This multicenter randomized controlled trial enrolled patients between 18 and 75 years old with an acceptably reduced intra-articular distal radial fracture. Patients were randomized to nonoperative treatment or to operative treatment. The primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) score after 12 months. Secondary outcome measures were the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; the Short Form-36 (SF-36) questionnaire; a visual analog scale for pain; range of motion; grip strength; radiographic parameters; and complications. Analyses followed the intention-to-treat principle.
A total of 96 patients were randomized, and 90 (46 in the nonoperative group and 44 in the operative group) were included in the analysis. Patients treated in the operative group had significantly better functional outcomes measured with the PRWE at 6 weeks, 3 months, 6 months, and 1 year. Additionally, a 28% rate of subsequent surgery was identified in the nonoperative group.
Adult patients with an acceptably reduced intra-articular distal radial fracture have better functional outcomes for 12 months when treated operatively instead of nonoperatively. We therefore recommend surgical treatment for patients with these fractures.
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
When compared to other types of cancer, the prevalence of midgut neuroendocrine tumors (NET) has disproportionally increased over the past decades. To date, there has been very little progress in ...discovering (epi)genetic drivers and treatment options for these tumors. Recent microbiome research has revealed that enteroendocrine cells communicate with the intestinal microbiome and has provided novel treatment targets for various other cancer types. Hence, our aim was to analyze the role of the gut microbiome in midgut NET patients.
Fecal samples, prospectively collected from patients and control subjects, were analyzed with next generation 16S sequencing. Patients with neuroendocrine carcinomas and recent antibiotics use were excluded. Relevant variables were extracted from questionnaires and electronic health records. Microbial composition was compared between patients and controls as well as between groups within the patient cohort.
87 midgut NET patients and 95 controls were included. Midgut NET patients had a less rich and diverse gut microbiome than controls (p < 0.001). Moreover, we identified 31 differentially abundant species and a gut microbial signature consisting of 17 species that was predictive of midgut NET presence with an area under the receiver operating characteristic curve of 0.863. Gut microbial composition was not directly associated with the presence of the carcinoid syndrome, tumor grade or multifocality. Nonetheless, we did observe a potential link between microbial diversity and the presence of carcinoid syndrome symptoms within the subset of patients with elevated 5-hydroxyindolacetic acid levels.
Midgut NET patients have an altered gut microbiome which suggests a role in NET development and could provide novel targets for microbiome-based diagnostics and therapeutics.
To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant ...neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2'-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)(7), also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Introduction Malunion occurs in approximately 23% of non-operatively treated and 11% of operatively treated distal radius fractures. The decision whether to correct a malunion is primarily ...based on functional impairment and wrist pain. The purpose of this study was to assess the long-term functional outcomes of corrective osteotomies for symptomatic malunited distal radius fractures. Methods All consecutive corrective osteotomies of the distal radius performed in one centre between January 2009 and January 2016 were included. The primary outcome was the functional outcome assessed with the Disability of the Arm, Shoulder and Hand (DASH) and the Patient-Rated Wrist Evaluation (PRWE) score. Secondary outcomes were range of motion, grip strength, pain as indicated on the Visual Analogue Scale (VAS) before and after corrective osteotomy, radiological parameters, time to union and complications. Additionally, we aimed to determine if there were any difference in graft versus no graft usage. Results A total of 48 patients were included. The median age was 54.5 years (IQR 39–66) and 71% was female. The median time to follow-up was 27 months. The median DASH and PRWE score were respectively 10.0 (IQR 5.8–23.3) and 18.5. (6.5–37.0). Except for pronation and supination, range of motion and grip strength of the injured wrist were significantly less compared to the uninjured side. Palmar and dorsal flexion and radial and ulnar deviation of the injured wrist were significantly less compared with the uninjured side. VAS pain scores decreased significantly from 6.5 preoperative to 1.0 postoperative. The median time to union was 23 weeks (IQR 12–29.5). Eighteen patients (38%) had a complication for which additional treatment was required. Except for a significant difference in radial inclination and length after the corrective osteotomy in favour of graft usage, there were no significant differences between graft an no graft usage. Conclusions Corrective osteotomy is an effective method of treating symptomatic distal radius malunions with good long-term functional results, measured with the DASH and PRWE score, and improvement in radiographic parameters and pain scores. Additionally, no differences in functional outcomes were found between graft and no graft usage.
Introduction
The aim of this study was to develop and validate an easy to use clinical decision rule, applicable in the ED that limits the number of unnecessary cast immobilizations and diagnostic ...follow-up in suspected scaphoid injury, without increasing the risk of missing fractures.
Methods
A prospective multicenter study was conducted that consisted of three components: (1) derivation of a clinical prediction model for detecting scaphoid fractures in adult patients following wrist trauma; (2) internal validation of the model; (3) design of a clinical decision rule. The predictors used were: sex, age, swelling of the anatomic snuffbox, tenderness in the anatomic snuffbox, scaphoid tubercle tenderness, painful ulnar deviation and painful axial thumb compression. The outcome measure was the presence of a scaphoid fracture, diagnosed on either initial radiographs or during re-evaluation after 1–2 weeks or on additional imaging (radiographs/MRI/CT). After multivariate logistic regression analysis and bootstrapping, the regression coefficient for each significant predictor was calculated. The effect of the rule was determined by calculating the number of missed scaphoid fractures and reduction of suspected fractures that required a cast.
Results
A consecutive series of 893 patients with acute wrist injury was included. Sixty-eight patients (7.6%) were diagnosed with a scaphoid fracture. The final prediction rule incorporated sex, swelling of the anatomic snuffbox, tenderness in the anatomic snuffbox, painful ulnar deviation and painful axial thumb compression. Internal validation of the prediction rule showed a sensitivity of 97% and a specificity of 20%. Using this rule, a 15% reduction in unnecessary immobilization and imaging could be achieved with a 50% decreased risk of missing a fracture compared with current clinical practice.
Conclusions
This dataset provided a simple clinical decision rule for scaphoid fractures following acute wrist injury that limits unnecessary immobilization and imaging with a decreased risk of missing a fracture compared to current clinical practice.
Clinical prediction rule
1/(1 + EXP (−(0.649662618 × if man) + (0.51353467826 × if swelling anatomic snuffbox) + (−0.79038263985 × if painful palpation anatomic snuffbox) + (0.57681198857 × if painful ulnar deviation) + (0.66499549728 × if painful thumb compression)−1.685).
Trial registration
Trial register NTR 2544,
www.trialregister.nl
.
Myotonic dystrophy type 1 (DM1) is caused by toxicity of an expanded, noncoding (CUG)n tract in DM protein kinase (DMPK) transcripts. According to current evidence the long (CUG)n segment is involved ...in entrapment of muscleblind (Mbnl) proteins in ribonuclear aggregates and stabilized expression of CUG binding protein 1 (CUGBP1), causing aberrant premRNA splicing and associated pathogenesis in DM1 patients. Here, we report on the use of antisense oligonucleotides (AONs) in a therapeutic strategy for reversal of RNA-gain-of-function toxicity. Using a previously undescribed mouse DM1 myoblast-myotube cell model and DM1 patient cells as screening tools, we have identified a fully 2'-O-methyl-phosphorothioate-modified (CAG)7 AON that silences mutant DMPK RNA expression and reduces the number of ribonuclear aggregates in a selective and (CUG)n-length-dependent manner. Direct administration of this AON in muscle of DM1 mouse models in vivo caused a significant reduction in the level of toxic (CUG)n RNA and a normalizing effect on aberrant premRNA splicing. Our data demonstrate proof of principle for therapeutic use of simple sequence AONs in DM1 and potentially other unstable microsatellite diseases.
The purpose of this study was to summarize and evaluate results of three-dimensional (3D-) planned corrective osteotomies of malunited distal radius fractures. 3D-planning techniques provide the ...possibility to address 3D-deformity that conventional planning methods might not address. We systematically searched PubMed, EMBASE and the Cochrane library for studies that performed a 3D-planned corrective osteotomy on patients with a malunited distal radius fracture. Fifteen studies with a total of 68 patients were included in the analysis. In 96% of cases, the preoperatively present palmar tilt, radial inclination and ulnar variance showed statistically significant improvement postoperatively with restoration to within 5° or 2 mm of their normal values. Mean flexion–extension, pro-supination and grip strength showed statistically significant improvement (
p
< 0.05). Complications were reported in 11 out of 68 patients (16%). With the current advances in 3D printing technology, 3D-planned corrective osteotomies seem a promising technique in the treatment of complex distal radius malunions.
Level of evidence IV
Systematic review of case series, Level IV.
The aim of this study was to compare the cost-effectiveness and cost-utility between plaster cast immobilization and volar plate fixation for acceptably reduced intra-articular distal radial ...fractures.
A cost-effectiveness analysis was conducted as part of a randomized controlled trial comparing operative (volar plate fixation) with nonoperative (plaster cast immobilization) treatment in patients between 18 and 75 years old with an acceptably reduced intra-articular distal radial fracture. Health-care utilization and use of resources per patient were documented prospectively and included direct medical costs, direct non-medical costs, and indirect costs. All analyses were performed according to the intention-to-treat principle.
The mean total cost per patient was $291 (95% bias-corrected and accelerated confidence interval bcaCI = -$1,286 to $1,572) higher in the operative group compared with the nonoperative group. The mean total number of quality-adjusted life-years (QALYs) gained at 12 months was significantly higher in the operative group than in the nonoperative group (mean difference = 0.15; 95% bcaCI = 0.056 to 0.243). The difference in the cost per QALY (incremental cost-effectiveness ratio ICER) was $2,008 (95% bcaCI = -$9,608 to $18,222) for the operative group compared with the nonoperative group, which means that operative treatment is more effective but also more expensive. Subgroup analysis including only patients with a paid job showed that the ICER was -$3,500 per QALY for the operative group with a paid job compared with the nonoperative group with a paid job, meaning that operative treatment is more effective and less expensive for patients with a paid job.
The difference in QALYs gained for the operatively treated group was equivalent to an additional 55 days of perfect health per year. In adult patients with an acceptably reduced intra-articular distal radial fracture, operative treatment is a cost-effective intervention, especially in patients with paid employment. Operative treatment is slightly more expensive than nonoperative treatment but provides better functional results and a better quality of life.
Economic and Decision Analysis Level I. See Instructions for Authors for a complete description of levels of evidence.
Fever of Unknown Origin: the Value of FDG-PET/CT Kouijzer, Ilse J.E.; Mulders-Manders, Catharina M.; Bleeker-Rovers, Chantal P. ...
Seminars in nuclear medicine,
March 2018, 2018-03-00, 20180301, Letnik:
48, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3°C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. The ...differential diagnosis of FUO can be subdivided in four categories: infections, malignancies, noninfectious inflammatory diseases, and miscellaneous causes. In most cases of FUO, there is an uncommon presentation of a common disease. FDG-PET/CT is a sensitive diagnostic technique for the evaluation of FUO by facilitating anatomical localization of focally increased FDG uptake, thereby guiding further diagnostic tests to achieve a final diagnosis. FDG-PET/CT should become a routine procedure in the workup of FUO when diagnostic clues are absent. FDG-PET/CT appears to be a cost-effective routine imaging technique in FUO by avoiding unnecessary investigations and reducing the duration of hospitalization.
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