[Trigger finger: to operate or to inject?] / Trigger finger: opereren of injecteren?

Trigger finger is a common hand disorder in which swelling of the affected flexor-tendon results in triggering, locking or pain at the A1-pulley and impaired function of the finger. In this clinical lesson we describe 4 cases of patients with this condition, illustrating the clinical picture of trigger finger and how decisions regarding treatment are made. In typical cases the diagnosis is straight forward, but if the clinical presentation is less clear (e.g. in case if there is only pain at the A1-pully or a locked finger) making the diagnosis can be challenging. Conservative (doing nothing, orthosis, injection) and operative treatment options are discussed. Guiding principles are formulated which may help in choosing the most appropriate treatment for individual patients.

The association between echogenicity and progression of Dupuytren's disease (DD): Birth of an imaging biomarker?

BACKGROUND: The shift of focus towards disease-controlling treatments to prevent DD progression at an early stage underlines the need for objective and reliable measurements that can monitor and predict the course of disease. Ultrasound has been studied as a potential tool for this purpose. This study examined to what extent echogenicity of early DD nodules predicts clinical progression. METHODS: Sonographic assessments of Dupuytren's nodules were performed by the same observer on 151 participants as part of an ongoing prospective cohort study on the course of DD. Echogenicity was assessed by determining the greyness of a nodule relative to the surrounding tissue, using ImageJ software. Progression of disease was defined as 1) an increase in total passive extension deficit (TPED) of ≥15 degrees and 2) surgical intervention of the examined ray, both occurring after the sonographic assessment. The associations between echogenicity and time to progression were estimated using Cox-regression models. RESULTS: The association between echogenicity and time to TPED progression showed that for every additional decrease of 1% in relative greyness (darker image) of a nodule, the risk of TPED progression during follow-up increases by 3.4% (hazard ratio [HR] = 0.966, 95% confidence interval [CI]: 0.935-0.966). Similarly, echogenicity was also associated with time to surgical intervention (HR = 0.967, 95% CI: 0.938-0.997), which indicates a higher risk for surgery during follow-up for darker nodules. CONCLUSIONS: These results suggest that echogenicity is predictive of the prognosis of the early stages of DD and might potentially be used as a prognostic imaging biomarker in the future.

A microfluidic optimal experimental design platform for forward design of cell-free genetic networks.

Cell-free protein synthesis has been widely used as a "breadboard" for design of synthetic genetic networks. However, due to a severe lack of modularity, forward engineering of genetic networks remains challenging. Here, we demonstrate how a combination of optimal experimental design and microfluidics allows us to devise dynamic cell-free gene expression experiments providing maximum information content for subsequent non-linear model identification. Importantly, we reveal that applying this methodology to a library of genetic circuits, that share common elements, further increases the information content of the data resulting in higher accuracy of model parameters. To show modularity of model parameters, we design a pulse decoder and bistable switch, and predict their behaviour both qualitatively and quantitatively. Finally, we update the parameter database and indicate that network topology affects parameter estimation accuracy. Utilizing our methodology provides us with more accurate model parameters, a necessity for forward engineering of complex genetic networks.

Transcription and Translation in Cytomimetic Protocells Perform Most Efficiently at Distinct Macromolecular Crowding Conditions.

The formation of cytomimetic protocells that capture the physicochemical aspects of living cells is an important goal in bottom-up synthetic biology. Here, we recreated the crowded cytoplasm in liposome-based protocells and studied the kinetics of cell-free gene expression in these crowded containers. We found that diffusion of key components is affected not only by macromolecular crowding but also by enzymatic activity in the protocell. Surprisingly, size-dependent diffusion in crowded conditions yielded two distinct maxima for protein synthesis, reflecting the differential impact of crowding on transcription and translation. Our experimental data show, for the first time, that macromolecular crowding induces a switch from reaction to diffusion control and that this switch depends on the sizes of the macromolecules involved. These results highlight the need to control the physical environment in the design of synthetic cells.

Reliability and Interpretability of Sonographic Measurements of Palmar Dupuytren Nodules.

PURPOSE: In the future, it is expected that treatment of Dupuytren disease (DD) may shift toward control of early disease. Ultrasound might be an accurate method to measure the outcome of such treatment. The aim of this study was to assess the reliability of sonographic measurement of palmar nodules. METHODS: Fifty patients with nodules characteristic for early disease were assessed with ultrasound by 2 observers. Four different aspects of DD nodules were measured in the transversal and sagittal planes, width, depth, circumference, and area. The intra- and interobserver reliabilities were calculated using the intraclass correlation coefficient (ICC). The standard error of measurement (SEM) and the smallest detectable change (SDC) were also calculated for each aspect. RESULTS: The intraobserver reliability was good (ICC, 0.724 [0.562-0.833] to 0.886 [0.808-0.934]), except for width in the sagittal direction (ICC, 0.671 [0.484-0.799]). The interobserver reliability was moderate (ICC, 0.385 [0.126-0.596] to 0.757 [0.538-0.869]). The intraobserver ICCs of area were highest (transverse, 0.847 [0.744-0.893]; sagittal, 0.886 [0.808-0.934]). The SEM and SDC of area were 6.1 and 16.9 mm2 in the transverse and 8.0 and 22.2 mm2 in the sagittal plane. CONCLUSIONS: The intraobserver reliability of sonographic assessment of DD nodules is good. The measurement of area is the most reliable and is, therefore, recommended for future studies. However, even single-observer measurements have a clear dispersion, and a change beyond 16.9 (61%) and 22.2 mm2 (79%) has to be observed in the transverse and sagittal planes, respectively, before it can be considered as regression or progression. CLINICAL RELEVANCE: Repeated ultrasonographic measurements in DD should ideally be done by a single observer, using area of the nodule in the sagittal plane. Change beyond 16.9 (transverse) and 22.2 (sagittal) mm2 can be considered as a real change in nodule size.

Impacts of temperature on evolution of char structure during pyrolysis of lignin.

This study investigated the pyrolysis of lignin pyrolysis in a temperature region from 200 to 800 °C, aiming to understand influence of pyrolysis temperature on evolution of structures of the resulting char. The results showed that fusion of the ring structure initiated at 200 °C, where the C/H ratio in the char was equal to that in naphthalene (two fused rings). The C/H ratio in the char obtained at 350 °C corresponded to that in pyrene (four fused rings), while the char produced at 550 °C was equivalent to 20 fused benzene rings in terms of C/H ratio. The increasing pyrolysis temperature also shifted the oxygen-containing functionalities such as the carbonyl, esters, ketones in the bio-oil to the ether functionality that had a higher thermal stability. The DRIFTS study of pyrolysis of lignin showed that drastic changes of the functionalities and the internal structure of the char occurred in a narrow temperature region from 520 to 530 °C. The carbonyl functionality and the aliphatic structure were eliminated, and new conjugated π-bond systems formed.

Imaging for Dupuytren disease: a systematic review of the literature.

BACKGROUND: As treatment of Dupuytren disease (DD) is expected to shift towards prevention of progression, the use of imaging in patients with DD becomes more important. In this systematic review an overview is given of the different methods for and applications of imaging for DD that have been described. METHODS: The MEDLINE and EMBASE databases were searched for articles reporting the use of imaging in patients with DD, published before May 17, 2018. Studies were systematically examined in two rounds by two observers according to the PRISMA systematic. All studies containing original data on imaging for DD were considered for inclusion. RESULTS: Three hundred and seven unique studies were identified, of which 23 were included in the study. Only studies on the use of ultrasound (US) and magnetic resonance imaging (MRI) were identified. Broadly, articles could be divided into 5 categories. Seven studies were found on diagnosis, two on measurement of disease extent, four on measurement of disease activity, seven on guidance of minimally invasive procedures and five studies on evaluation of treatment. According to the Oxford CEBM, the levels of evidence were low, ranging from level 3 to 5. CONCLUSIONS: A variety of applications for US and MRI for patients with DD has been described. Based on the results of this review, the largest value for imaging lies in the measurement of disease activity and the follow-up of treatment of patients with early stage disease. Unfortunately, the overall level of evidence of the available literature was low. Future research is necessary to define the exact value of US and MRI in the management of patients with DD.

Protein Synthesis in Coupled and Uncoupled Cell-Free Prokaryotic Gene Expression Systems.

Secondary structure formation of mRNA, caused by desynchronization of transcription and translation, is known to impact gene expression in vivo. Yet, inactivation of mRNA by secondary structures in cell-free protein expression is frequently overlooked. Transcription and translation rates are often not highly synchronized in cell-free expression systems, leading to a temporal mismatch between the processes and a drop in efficiency of protein production. By devising a cell-free gene expression platform in which transcriptional and translational elongation are successfully performed independently, we determine that sequence-dependent mRNA secondary structures are the main cause of mRNA inactivation in in vitro gene expression.

Macromolecular crowding creates heterogeneous environments of gene expression in picolitre droplets.

Understanding the dynamics of complex enzymatic reactions in highly crowded small volumes is crucial for the development of synthetic minimal cells. Compartmentalized biochemical reactions in cell-sized containers exhibit a degree of randomness due to the small number of molecules involved. However, it is unknown how the physical environment contributes to the stochastic nature of multistep enzymatic processes. Here, we present a robust method to quantify gene expression noise in vitro using droplet microfluidics. We study the changes in stochasticity in the cell-free gene expression of two genes compartmentalized within droplets as a function of DNA copy number and macromolecular crowding. We find that decreased diffusion caused by a crowded environment leads to the spontaneous formation of heterogeneous microenvironments of mRNA as local production rates exceed the diffusion rates of macromolecules. This heterogeneity leads to a higher probability of the molecular machinery staying in the same microenvironment, directly increasing the system's stochasticity.

Transcultural adaptation and validation of the Spanish version of EUROQUEST.

INTRODUCTION: The specific diagnosis of toxic encephalopathy (TE) by chronic exposure to neurotoxics presents difficulties, mainly due to lack of consensus of clinical diagnostic criteria. The EUROQUEST (EQ) is a multicultural tool proposed for using in epidemiological studies on neurotoxicity. The aim of this study was to validate the Spanish version of this questionnaire for using as a diagnostic and prevention tool in the workplace. METHODS: After translation and cultural adaptation, leading to a final questionnaire in Spanish, validation was performed by asking a total of 759 people to complete the questionnaire, of whom 292 were workers exposed to neurotoxic solvents, 391 non-exposed workers, and 22 patients diagnosed with chronic alcoholism. RESULTS: In the analysis of the reliability, the Cronbach α value for the questionnaire was 0.94, indicating very high internal consistency. The test-retest reproducibility analysis was highly significant (r=0.91, P<.001). In the analysis of the validity, comparing the three study groups, the mean scores of the questions included in each of the dimensions of the test (ANOVA) detected major differences in the dimensions that assess cognitive symptoms, depressive disorders, sleep and psychopathological symptoms. After factor analysis obtained a total of nine axes, allowing a clear distinction between the three study groups.

Decolorization and mineralization of reactive dyes, by the H2O2/UV process with electrochemically produced H2O2.

Decolorization of Reactive Red 238, Reactive Orange 16, Reactive Black 5 and Reactive Blue 4 was studied in the UV/H2O2 process with H2O2 being produced electrochemically. The experimental results show that decolorization increased considerably when switching on the electrochemical production of H2O2. Complete decolorization (>99%) was achieved for all dyes under the applied experimental conditions, partial mineralization (49-85%) was obtained, which depends on the type of dye. Reactive Red 238 was used to investigate operational parameters and it was found that decolorization was influenced by the applied electrical current of the electrochemical cell and flow rate. Decolorization and mineralization of Reactive Red 238 can be described by pseudo-first order kinetics. It was found that the initial concentration of Reactive Red 238 has a negative influence on the pseudo-first order reaction constant.

Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene.

The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7mg/m(3)) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.