[What effect does a face mask have on the surface of the eye?] / Wat is het effect van een mondmasker op het oogoppervlak?

Face masks are widely used in dental practices, but little is known about the potential adverse effects of wearing a face mask, covering the mouth-and-nose area, on the condition of the eyes. During COVID-19 times, more eye-related complaints, such as irritated, burning or dry eyes, have been reported and observed as a result of the (mandatory) use of face masks, The combination of wearing a face mask and working on a computer appears to also cause more dry-eye complaints. Symptoms such as headache, double vision, blurry vision, irritated red eyes and/or dry eyes are often diagnosed under the collective term asthenopia, also called 'eye strain' in the literature in English. These work-related complaints are often accepted as 'normal', especially because they develop during the day. During the COVID-19 period, more knowledge has been gained about the use of face masks, face shields and eye health. It is therefore possible to consider whether personal protection with a face mask in the dental practice can cause eye-related complaints.

Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals.

BACKGROUND: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. AIM: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). METHODS: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. RESULTS: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL). CONCLUSION: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.

Agreement in dry eye management between optometrists and general practitioners in primary health care in the Netherlands.

PURPOSE: To investigate the agreement in dry eye care management between general practitioners (GPs) and optometrists in the Netherlands. METHODS: A web-based survey was used to investigate the agreement in symptoms associated with dry eye, causes of developing dry eye, and investigative techniques used in practice, between GPs and optometrists. Additional questions surveyed knowledge of the latest research, and co-management of dry eye disease in primary healthcare. The anonymised questionnaire contained 16 forced-choice questions with Likert scales, and was sent to 1471 general medical practitioners and 870 registered optometrists. The response data was stored on an online database, and was converted directly to text format for analysis using SPSS 21 statistical analysis software. RESULTS: 138 optometrists and 93 GPs responded to the survey (Cronbach α=0.885, optometrists, and 0.833, GPs). Almost no agreement was found for all the questions: a statistically significant difference (Chi-square p<0.0001) was found between the optometrists and GPs in the use of investigative techniques, associating symptoms, causes of dry eye (p>0.0001), and dry eye symptoms, except for 'burning sensation of the eye' and 'irritation of the eye' as agreed symptoms, and agreement that dry eye is an age-related disease. CONCLUSIONS: As the optometrist and the GP are the gatekeepers for secondary healthcare, the fundamental differences in the methods of investigation and interpretation of dry eye-related symptoms, the possible cause of developing dry eye disease, and the therapy given by GPs and optometrists in the Netherlands, may have a significant impact on consistency of patient care.

Selfish element maintains sex in natural populations of a parasitoid wasp.

Genomic conflicts between heritable elements with different modes of inheritance are important in the maintenance of sex and in the evolution of sex ratio. Generally, we expect sexual populations to exhibit a 1:1 sex ratio. However, because of their biology, parasitoid wasps often exhibit a female-biased sex ratio. Sex-ratio distorters can further alter this optimum, sometimes leading to the complete loss of sexual reproduction. In the parasitoid wasp Trichogramma kaykai ca. 4-26% of females in field populations are infected with a bacterial sex-ratio distorter, Wolbachia, allowing virgin mothers to produce daughters. In some micro-Hymenoptera these infections have led to the complete loss of sex, but in field populations of T. kaykai the proportion of individuals infected remains relatively stable. We tested several hypotheses to explain this low infection level, including inefficient and horizontal transmission of Wolbachia, suppressor genes negating the effect of Wolbachia and the presence of male-biasing sex-ratio distorters. Here, a male-biasing sex-ratio distorter, a parasitic B chromosome, causing females to produce only sons, keeps the frequency of Wolbachia low. The male-biasing factor of T. kaykai is the second known case of a B chromosome manipulating the reproduction of a parasitoid wasp.

Mutations in the glucocorticoid receptor DNA-binding domain mimic an allosteric effect of DNA.

Two previously isolated mutations in the glucocorticoid receptor DNA-binding domain (DBD), S459A and P493R, have been postulated to mimic DNA-induced conformational changes in the glucocorticoid receptor DBD, thereby constitutively triggering an allosteric mechanism in which binding of specific DNA normally induces the exposure of otherwise silent glucocorticoid receptor transcriptional activation surfaces. Here we report the three-dimensional structure of the free S459A and P493R mutant DBDs as determined by NMR spectroscopy. The free S459A and P493R structures both display the conformational changes in the DBD dimerization interface that are characteristic of the DNA-bound wild-type DBD, confirming that these mutations mimic an allosteric effect of DNA. A transition between two packing arrangements of the DBD hydrophobic core provides a mechanism for long-range transmission of conformational changes, induced either by the mutations or by DNA binding, to protein-protein contact surfaces.

Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations.

The solution structure of the glucocorticoid receptor (GR) DNA-binding domain (DBD), consisting of 93 residues, has been refined from two and three-dimensional NMR data using an ensemble iterative relaxation matrix approach followed by direct NOE refinement with DINOSAUR. A set of 47 structures of the rat GR fragment Cys440-Arg510 was generated with distance geometry and further refined with a combination of restrained energy minimization and restrained molecular dynamics in a parallel refinement protocol. Distance constraints were obtained from an extensive set of NOE build-up curves in H2O and 2H2O via relaxation matrix calculations (1186 distance constraints from NOE intensities, 10 phi and 22 chi 1 dihedral angle constraints from J- coupling data were used for the calculations). The root-mean-square deviation values of the 11 best structures on the well-determined part of the protein (Cys440 to Ser448, His451 to Glu469 and Pro493 to Glu508) are 0.60 A and 1.20 A from the average for backbone and all heavy atoms, respectively. The final structures have R-factors around 0.40 and good stereochemical qualities. The first zinc-coordinating domain of the GR DBD is very similar to the crystal structure with a root-mean-square difference of 1.4 A. The second zinc-coordinating domain is still disordered in solution. No secondary structure element is found in this domain in the free state. As suggested by crystallographic studies on the estrogen receptor DBD-DNA and GR DBD-DNA complexes, part of this region will form a distorted helix and the D-box will undergo a conformational change upon cooperative binding to DNA.

NMR structural studies on the zinc finger domains of nuclear hormone receptors.

This chapter presents an overview of the application of modern NMR methods in structural studies of the DNA binding domains (DBDs) of nuclear hormone receptors. The DBDs studied so far comprise those of the glucocorticoid, estrogen, retinoic acid and retinoid X receptors. NMR spectroscopy has allowed the elucidation of the first structures of this family of C4-type zinc fingers, which led to a better understanding of their role in gene regulation. Crystallographic studies provided insight in protein-protein and protein-DNA interactions. Subsequent studies, applying NMR, have provided deeper insight into a diversity of issues concerning these proteins, ranging from backbone dynamics and metal coordination to the interaction of these domains with their DNA target sites. From this work a picture emerges of a class of closely related zinc-binding proteins which, despite their strong sequence homology, exhibit interesting structural and functional differences between members of different subfamilies.

New approaches with the Chem-1 creatinine determination.

Three modifications of the Chem-1 determination of serum creatinine were tested. Two different algorithms developed for compensating the interference of bilirubin were compared with the current one by analysing bilirubin-enriched albumin solutions and 82 icteric serum samples. A number of known other interfering substances were also tested. The modification involving parallel bichromatic measurement plus bilirubin correction appeared to give the best performance. However, despite the improvements, the determination is not yet completely satisfactory.

Sequence-informative fragmentation of peptides up to a molecular weight of 4.6 kDa in plasma-desorption mass spectrometry.

The potential of plasma-desorption mass spectrometry (PDMS) in peptide sequencing is investigated. This paper shows that PDMS spectra recorded for longer times and using larger amounts of peptide than used for obtaining molecular weight information, provides sequence information on peptides of up to 4.5 kDa molecular weight. This approach strongly enhances the utility of PDMS for validation of the sequence of recombinant peptides.