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Background: During the COVID-19 pandemic, psoriasis care underwent significant changes in consultation methods and treatment management. However, comprehensive data on these changes and patient perceptions are limited. Aims: To evaluate the pandemic's implications on psoriasis patients, focusing on access to information, consultation methods, patient satisfaction, disease control assessment, and treatment management changes. Methods: A multicenter cross-sectional survey was performed in psoriasis patients from 4 dutch hospitals during the second wave of the pandemic. Results: Among 551 respondents, approximately 55% received information their treatment in relation to COVID-19 from their treating physician, while 16.3% sought information online. Consultation methods were shifted to remote formats for 43.6% of patients, primarily via phone and the shift was often initiated by physicians. Overall patient satisfaction during the pandemic scored high (8.0), with remote consultations scoring between 8.0–9.0. Patients on biological treatment reported better disease control (8.0), compared to those on topical (6.0) or conventional systemic treatments (7.0). However, within the systemic treatment group and biologics group, a notable percentage interrupted (16.3% resp. 12.9%) or discontinued treatment (14.1 resp. 10.6%) during the pandemic. Disease control was moderate-to-good assessed by 75% of patients receiving face-to-face and 68% receiving remote consultations. Conclusion: Remote care appears to be a viable alternative to face-to-face consultations, with potential benefits in enhancing access to information provided by treating physicians. [ABSTRACT FROM AUTHOR]

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors. Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations. Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p  < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p  = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p  = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning. Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer-nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer., (© 2023. The Author(s).)

Background: The risk of SARS-CoV-2 infection does not appear to be increased for psoriasis patients using biologics compared to those on other treatments, but evidence is still limited., Objectives: (1) to estimate the prevalence of SARS-CoV-2 infection in patients with psoriasis, (2) to compare SARS-CoV-2 infection rates for different psoriasis treatments groups (biologic vs. systemic conventional vs. topical therapy) corrected for confounders and (3) to describe patients with severe COVID-19 for all treatment groups., Methods: In this cross-sectional cohort study all patients received a questionnaire to gather data on psoriasis treatment, SARS-CoV-2 infections and related risk factors. Simultaneously, they underwent a blood test to screen for antibodies to SARS-CoV-2 N-antigen. Prevalence of SARS-CoV-2 infections was calculated and logistic regression and Cox proportional-hazards models were performed to determine the association between treatment group and SARS-CoV-2 infection risk, corrected for confounders. Patients with severe COVID-19 disease were described and the mortality rate per treatment group was calculated for the target population., Results: Patients were included between April 12 2021 and October 31 2021. Of 551 patients, 59 (10.7% (CI95% 8.3-13.6)) had experienced a SARS-CoV-2 infection, based on questionnaire data combined with serological data. In our study cohort, corrected for confounders, biologic or non-biologic systemic therapy users did not appear to have increased SARS-CoV-2 infection risk compared to patients using other treatment. Only 4 hospitalizations (0.7% (CI95% 0.2-1.0) were reported in our study population and no ICU admissions were reported. The rough mortality rate in the target cohort was 0.32% (CI95% 0.13-0.66) in all treatment groups., Conclusions: Corrected for risk-mitigating behavior and vaccination status, a higher SARS-CoV-2 incidence for biologics or non-biologics systemics compared to other treatments could not be proven. Severe cases were infrequent in all treatment groups. This finding further strengthens treatment recommendations that systemic therapies for patients with psoriasis do not require preventive cessation for reduction of SARS-CoV-2 infection risk.

Molecular motors often work in teams to move a cellular cargo. Yet measuring the forces exerted by each motor is challenging. Using a sensor made with denatured ssDNA and multi-color fluorescence, we measured picoNewtons of forces and nanometer distances exerted by individual constrained kinesin-1 motors acting together while driving a common microtubule in vitro . We find that kinesins primarily exerted less than 1 pN force, even while the microtubule is bypassing artificial obstacles of 20-100 nanometer size. Occasionally, individual forces increase upon encountering obstacles, although at other times they do not, with the cargo continuing in a directional manner. Our high-throughput technique, which can measure forces by many motors simultaneously, is expected to be useful for many different types of molecular motors.

The global prevalence of antibiotic-resistant bacteria has increased the risk of dangerous infections, requiring rapid diagnosis and treatment. The standard method for diagnosis of bacterial infections remains dependent on slow culture-based methods, carried out in central laboratories, not easily extensible to rapid identification of organisms, and thus not optimal for timely treatments at the point-of-care (POC). Here, we demonstrate rapid detection of bacteria by combining electrochemical immunoassays (EC-IA) for pathogen identification with confirmatory quantitative mass spectral immunoassays (MS-IA) based on signal ion emission reactive release amplification (SIERRA) nanoparticles with unique mass labels. This diagnostic method uses compatible reagents for all involved assays and standard fluidics for automatic sample preparation at POC. EC-IA, based on alkaline phosphatase-conjugated pathogen-specific antibodies, quantified down to 10 4 bacteria per sample when testing Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa lysates. EC-IA quantitation was also obtained for wound samples. The MS-IA using nanoparticles against S. aureus , E. coli , Klebsiella pneumoniae , and P. aeruginosa allowed selective quantitation of ∼10 5 bacteria per sample. This method preserves bacterial cells allowing extraction and amplification of 16S ribosomal RNA genes and antibiotic resistance genes, as was demonstrated through identification and quantitation of two strains of E. coli , resistant and nonresistant due to β-lactamase cefotaximase genes. Finally, the combined immunoassays were compared against culture using remnant deidentified patient urine samples. The sensitivities for these immunoassays were 83, 95, and 92% for the prediction of S. aureus , P. aeruginosa , and E. coli or K. pneumoniae positive culture, respectively, while specificities were 85, 92, and 97%. The diagnostic platform presented here with fluidics and combined immunoassays allows for pathogen isolation within 5 min and identification in as little as 15 min to 1 h, to help guide the decision for additional testing, optimally only on positive samples, such as multiplexed or resistance gene assays (6 h).

How cargoes move within a crowded cell-over long distances and at speeds nearly the same as when moving on unimpeded pathway-has long been mysterious. Through an in vitro force-gliding assay, which involves measuring nanometer displacement and piconewtons of force, we show that multiple mammalian kinesin-1 (from 2 to 8) communicate in a team by inducing tension (up to 4 pN) on the cargo. Kinesins adopt two distinct states, with one-third slowing down the microtubule and two-thirds speeding it up. Resisting kinesins tend to come off more rapidly than, and speed up when pulled by driving kinesins, implying an asymmetric tug-of-war. Furthermore, kinesins dynamically interact to overcome roadblocks, occasionally combining their forces. Consequently, multiple kinesins acting as a team may play a significant role in facilitating smooth cargo motion in a dense environment. This is one of few cases in which single molecule behavior can be connected to ensemble behavior of multiple motors., Competing Interests: MT Marco Tjioe is affiliated with Element Biosciences. The author has no other competing interests to declare. SS, RV, AT, CB, KT, YC, PS No competing interests declared, (© 2019, Tjioe et al.)

We develop magnetic cytoskeleton affinity (MiCA) purification, which allows for rapid isolation of molecular motors conjugated to large multivalent quantum dots, in miniscule quantities, which is especially useful for single-molecule applications. When purifying labeled molecular motors, an excess of fluorophores or labels is usually used. However, large labels tend to sediment during the centrifugation step of microtubule affinity purification, a traditionally powerful technique for motor purification. This is solved with MiCA, and purification time is cut from 2 h to 20 min, a significant time-savings when it needs to be done daily. For kinesin, MiCA works with as little as 0.6 μg protein, with yield of ∼27%, compared to 41% with traditional purification. We show the utility of MiCA purification in a force-gliding assay with kinesin, allowing, for the first time, simultaneous determination of whether the force from each motor in a multiple-motor system drives or hinders microtubule movement. Furthermore, we demonstrate rapid purification of just 30 ng dynein-dynactin-BICD2N-QD (DDB-QD), ordinarily a difficult protein-complex to purify.

Objective: To gain insight into the trends in the use of psychostimulants among adults., Design: Retrospective database study., Methods: We selected data on adults (≥ 18 years) who had had a minimum of 2 prescriptions for a psychostimulant drug within 1 year from IADB.nl, a Netherlands database of filled prescriptions (59 public pharmacies, approximately 600,000 patients). We calculated both the number of new users and the total number of users of psychostimulants per year in the period 2004-2014. We also assessed which agent was the most commonly prescribed psychostimulant drug and who had initiated treatment., Results: The number of adults who were prescribed psychostimulants (methylphenidate, dexamphetamine and amphetamine) increased from 1.5 per 1000 adults in 2004 to 7.8 per 1000 adults in 2014. Users were mainly male (63.0%) and methylphenidate was the most frequently prescribed agent (85.7%). The number of new users of these agents increased from 0.5 to 1.5 per 1000 adults, and the greatest increase was observed among young adults (< 30 years). The increase in new users seems to have stabilized since 2012. Around 40% of new treatments were initiated by the GP., Conclusion: The large increase in the number of adults who are prescribed psychostimulants seems mainly to be the result of an increase in the number of new users, especially among young adults. As psychostimulants are only approved for the treatment of ADHD in children from 6 years of age and in adolescents, short- and long-term effects and side effects of these drugs need to be better assessed in the adult population.

To measure nanometric features with super-resolution requires that the stage, which holds the sample, be stable to nanometric precision. Herein we introduce a new method that uses conventional equipment, is low cost, and does not require intensive computation. Fiduciary markers of approximately 1 µm x 1 µm x 1 µm in x, y, and z dimensions are placed at regular intervals on the coverslip. These fiduciary markers are easy to put down, are completely stationary with respect to the coverslip, are bio-compatible, and do not interfere with fluorescence or intensity measurements. As the coverslip undergoes drift (or is purposely moved), the x-y center of the fiduciary markers can be readily tracked to 1 nanometer using a Gaussian fit. By focusing the light slightly out-of-focus, the z-axis can also be tracked to < 5 nm for dry samples and <17 nm for wet samples by looking at the diffraction rings. The process of tracking the fiduciary markers does not interfere with visible fluorescence because an infrared light emitting diode (IR-LED) (690 and 850 nm) is used, and the IR-light is separately detected using an inexpensive camera. The resulting motion of the coverslip can then be corrected for, either after-the-fact, or by using active stabilizers, to correct for the motion. We applied this method to watch kinesin walking with ≈ 8 nm steps.

The scabies mite is an ectoparasite able to infest humans. Its clinical presentation is typical, although in immunocompromised, mentally retarded and elderly patients the clinical presentation may be altered. Diagnosis may therefore be difficult in such patient groups, who often reside in nursing homes. Because delay in diagnosis may induce rapid spread of the scabies mite, immediate diagnosis and treatment are necessary. Normal scabies (scabies vulgaris) and crusted scabies (scabies crustosa, scabies norvegica), although sometimes difficult to diagnose, especially in the elderly, are fortunately quite easy to treat. However, the elderly patient may experience toxicity from local or systemic scabicidal treatment. Single cases of scabies vulgaris should be treated with permethrin cream because of its outstanding efficacy and favourable adverse events profile. Scabies outbreaks and cases of scabies crustosa can easily be managed using combination therapy consisting of topical application of permethrin and two oral doses of ivermectin 200 microg/kg (administered 1 week apart). In addition to treatment of the scabies infestation, preventative measures are necessary, particularly in nursing homes.

Objective: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ., Design: Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment., Setting: Forty outpatient dermatology centers in 11 European countries., Patients: Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression., Interventions: Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated., Main Outcome Measures: Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale)., Results: At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months., Conclusion: Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis.

Recently, topical macrolide immunomodulators have been successfully introduced in the treatment of atopic dermatitis. With the growing interest in this new line of topical immunosuppressants, research into the efficacy of these medicines in other T-cell-mediated skin diseases, such as psoriasis, lichen planus, and even vitiligo, is expanding rapidly. It is generally accepted that autoimmune factors play an important role in vitiligo. In this article, the possible use and mechanism of topical macrolide immunomodulators in the treatment of vitiligo are discussed, together with the current state of clinical studies and case reports. These limited reports indicate that topical macrolide immunomodulators may play a role in the treatment of vitiligo, particularly in areas where use of potent corticosteroids is contraindicated.

TNF-alpha is known to play an important role in UV-induced immunomodulation and photodamage. It plays a role in UVB-mediated induction of apoptosis and is a strong inducer of the c-Jun N-terminal kinase (JNK) pathway, which eventually leads to the loss of dermal collagen and elastin content. Recently chimeric anti-TNF-alpha has been introduced as a therapy for rheumatoid arthritis. The aim of the present study was to investigate the effect of anti-TNF-alpha treatment on UV-induced DNA damage, apoptosis, and induction of matrix metallo proteinases. Twelve patients with rheumatoid arthritis were included and irradiated with 2 MED broadband UVB before and after administration of 0.5 mg/kg anti-TNF-alpha monoclonal antibody. Twenty-four hours after irradiation biopsies were taken. Frozen and paraffin sections were stained for p53, c-Jun, phosphorylated c-Jun, sunburn cells and MMP-1. No significant changes were observed in the expression of p53 and sunburn cells and MMP-1 content after treatment with anti-TNF-alpha, whereas a slight but significant decrease in c-Jun and phosphorylated c-Jun expression was noted (P = 0.0250 and P = 0.0431, respectively). Our results showed no influence of anti-TNF-alpha on UV response at therapeutic doses in patients with rheumatoid arthritis.

Narrow band UVB is succeeding psoralen and UVA irradiation as the main treatment of vitiligo vulgaris in several European countries. Vitamin B12 and folic acid deficiency in some vitiligo patients has prompted researchers to investigate the efficacy of these vitamins in the treatment of vitiligo. In the present controlled study we investigated the value of narrow band UVB phototherapy in the treatment of vitiligo and the possible additive effect of vitamin B12 and folic acid. Twenty-seven patients with long-term stable vitiligo were included and randomized in a "UVB only" (UVB) or "UVB combined with vitamin B12 and folic acid" (UVB+) group. Patients were irradiated thrice weekly for one year, whilst repigmentation was carefully monitored. In 92% (25/27) of the patients up to 100% repigmentation was seen. Repigmentation was notable in lesions on the face, neck and throat, lower arm, chest, back and lower legs, whilst repigmentation on the hands, wrists, feet and ankles proved to be minimal. Maximum repigmentation rates did not differ significantly between the UVB group and the UVB+ group. Our study reconfirms that narrow band UVB phototherapy is an effective treatment for vitiligo and shows that co-treatment with vitamin B12 and folic acid does not improve the outcome of treatment of vitiligo with narrow band UVB phototherapy.