Contact allergy to rubber accelerators in consecutively patch tested Danish eczema patients: A retrospective observational study from 1990 to 2019.

BACKGROUND: Rubber accelerators are used in the production of rubber gloves and may cause contact allergy. OBJECTIVES: To estimate long-term trend and prevalence of contact allergy to rubber accelerators for a 30-year period in Denmark, high-risk occupations, and exposures. METHODS: Data from all patients with contact dermatitis consecutively patch tested at the department of Skin and Allergy Gentofte hospital with the rubber accelerators from the European baseline series (EBS) from 1990 to 2019, were analysed. Further, patients under suspicion of rubber accelerator contact allergy were additionally patch-tested with rubber accelerators from the specialised rubber series from 2005 to 2019 and these were additional extracted. RESULTS: The overall prevalence of contact allergy to one or more of the rubber accelerators from the EBS series was 2.7% with a significant decline in the first 12-years, followed by a stable frequency in the past 18-years. Associations with occupational contact dermatitis, hand dermatitis, and leg/foot dermatitis were found. Wet-work occupations were most often affected and gloves the most frequent exposure. CONCLUSIONS: Contact allergy to one or more of the rubber accelerators from the EBS is frequent and has been unchanged for several decades, which calls for prevention.

Improvements in cuirass ventilation for airway surgery: origins in Copenhagen on the 70th anniversary of the first intensive care unit.

The first modern intensive care unit was established in Copenhagen 70 yr ago. This cornerstone of anaesthesia was largely based on experience gained using positive pressure ventilation to save hundreds of patients during the polio epidemic in 1952. Ventilation approaches, monitoring techniques, and pharmacological innovations have developed to such an extent that cuirass ventilation, which proved inadequate during the polio epidemic, might now have novel applications for both anaesthesia and treatment of the critically ill.

Immune and stem cell compartments of acetabular and femoral bone marrow in hip osteoarthritis patients.

OBJECTIVE: Hip osteoarthritis (OA) affects all components of the osteochondral unit, leading to bone marrow (BM) lesions, and unknown consequences on BM cell functionality. We analyzed the cellular composition in OA-affected acetabula compared to proximal femur shafts obtained of hip OA patients to reveal yet not explored immune and stem cell compartments. DESIGN: Combining flow cytometry, cellular assays and transcription analyses, we performed extensive ex vivo phenotyping of acetabular BM cells from 18 hip OA patients, comparing them with their counterparts from patient-matched femoral shaft BM samples. Findings were related to differences in skeletal sites and age. RESULTS: Acetabular BM had a greater frequency of T-lymphocytes, non-hematopoietic cells and colony-forming units fibroblastic potential than femoral BM. The incidence of acetabular CD45+CD3+ T-lymphocytes increased (95% CI: 0.1770 to 0.0.8416), while clonogenic hematopoietic progenitors declined (95% CI: -0.9023 to -0.2399) with age of patients. On the other side, in femoral BM, we observed higher B-lymphocyte, myeloid and erythroid cell frequencies. Acetabular mesenchymal stromal cells (MSCs) showed a senescent profile associated with the expression of survival and inflammation-related genes. Efficient osteogenic and chondrogenic differentiation was detected in acetabular MSCs, while adipogenesis was more pronounced in their femoral counterparts. CONCLUSION: Our results suggest that distinctions in BM cellular compartments and MSCs may be due to the influence of the OA-stressed microenvironment, but also acetabular vs femoral shaft-specific peculiarities cannot be excluded. These results bring new knowledge on acetabular BM cell populations and may be addressed as novel pathogenic mechanisms and therapeutic targets in OA.

Effects of different exercise intensity on bone mineral density in adults: a comparative systematic review and meta-analysis.

PURPOSE: The primary objective of the present systematic review and meta-analysis was to determine the effect of differing exercise intensity on (areal) bone mineral density (BMD) at lumbar spine and hip in adults by a comparative meta-analysis. METHODS: A systematic review of the literature according to the PRISMA statement included: (a) exercise trials, (b) with ≥two study arms that compared different exercise intensities, (c) intervention ≥6 months, (d) BMD assessments at lumbar spine (LS) or hip. Five electronic databases were scanned without language restrictions up to July 2021. The present analysis of exercise intensity was conducted as a mixed-effect meta-analysis and applied "type of exercise" and "study duration" as moderator in subgroup analyses. Outcome measures were standardized mean differences (SMD) for BMD changes at the LS, and hip. RESULTS: Eleven exercise studies with 26 study arms were included. Although the effect of high-intensity exercise was more pronounced on LS-BMD (SMD: 0.19, 95%-CI: 0.61 to -0.23) and hip-ROI (0.17, 0.38 to -0.04), we did not observe significant differences between the groups (LS-BMD: p=0.373 and hip-BMD: p=0.109). We observed a substantial level of heterogeneity between the trials for LS- but not for hip-BMD. Applying "type of exercise" and "study duration" as moderators did not significantly modify the differences between low and high exercise intensity on BMD at LS or hip. CONCLUSION: There is insufficient evidence for a superior effect of high-intensity exercise on areal BMD at lumbar spine and hip in people aged 50 years and older. Varying exercise intensity with periods of lower exercise intensity intermitted by higher intensity might be a promising option to address the issue of exercise intensities in intervention studies.

Sexual dysfunction in women with type 1 diabetes in Norway: A cross-sectional study on the prevalence and associations with physical and psychosocial complications.

AIM: To estimate the prevalence of sexual dysfunction in women with type 1 diabetes (T1D) compared with women without diabetes and to analyse associations between sexual dysfunction and the presence of chronic physical diabetes complications, diabetes distress and depression in women with T1D. METHODS: This cross-sectional study was conducted in Norway, and 171 women with T1D and 60 controls completed the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). Diabetes distress was assessed with the Problem Areas in Diabetes (PAID) scale. Data on diabetes complications were retrieved from medical records. We performed logistic regression to estimate differences in the prevalence of sexual dysfunction (defined as FSFI ≤26.55) between women with T1D and women without diabetes and to examine associations of sexual dysfunction with chronic diabetes complications, diabetes distress and depression in women with T1D. RESULTS: The prevalence of sexual dysfunction was higher in women with T1D (50.3%) compared with the controls (35.0%; unadjusted odds ratio [OR] 1.89 [95% confidence interval (CI) 1.06-3.37]; adjusted OR 1.93 [1.05-3.56]). In women with T1D, sexual dysfunction was associated with both diabetes distress (adjusted OR 1.03 [1.01-1.05]) and depression (adjusted OR 1.28 [1.12-1.46]), but there were no clear associations with chronic diabetes complications (adjusted OR 1.46 [0.67-3.19]). CONCLUSIONS: This study suggests that sexual dysfunction is more prevalent in women with T1D compared with women without diabetes. The study findings emphasize the importance of including sexual health in relation to diabetes distress and psychological aspects in diabetes care and future research.

Hypophosphatasia in adolescents and adults: overview of diagnosis and treatment.

This article provides an overview of the current knowledge on hypophosphatasia-a rare genetic disease of very variable presentation and severity-with a special focus on adolescents and adults. It summarizes the available information on the many known mutations of tissue-nonspecific alkaline phosphatase (TNSALP), the epidemiology and clinical presentation of the disease in adolescents and adults, and the essential diagnostic clues. The last section reviews the therapeutic approaches, including recent reports on enzyme replacement therapy (EnzRT).

A year-long immune profile of the systemic response in acute stroke survivors.

Stroke is a leading cause of cognitive impairment and dementia, but the mechanisms that underlie post-stroke cognitive decline are not well understood. Stroke produces profound local and systemic immune responses that engage all major innate and adaptive immune compartments. However, whether the systemic immune response to stroke contributes to long-term disability remains ill-defined. We used a single-cell mass cytometry approach to comprehensively and functionally characterize the systemic immune response to stroke in longitudinal blood samples from 24 patients over the course of 1 year and correlated the immune response with changes in cognitive functioning between 90 and 365 days post-stroke. Using elastic net regularized regression modelling, we identified key elements of a robust and prolonged systemic immune response to ischaemic stroke that occurs in three phases: an acute phase (Day 2) characterized by increased signal transducer and activator of transcription 3 (STAT3) signalling responses in innate immune cell types, an intermediate phase (Day 5) characterized by increased cAMP response element-binding protein (CREB) signalling responses in adaptive immune cell types, and a late phase (Day 90) by persistent elevation of neutrophils, and immunoglobulin M+ (IgM+) B cells. By Day 365 there was no detectable difference between these samples and those from an age- and gender-matched patient cohort without stroke. When regressed against the change in the Montreal Cognitive Assessment scores between Days 90 and 365 after stroke, the acute inflammatory phase Elastic Net model correlated with post-stroke cognitive trajectories (r = -0.692, Bonferroni-corrected P = 0.039). The results demonstrate the utility of a deep immune profiling approach with mass cytometry for the identification of clinically relevant immune correlates of long-term cognitive trajectories.

Superbenzene-Porphyrin Gas-Phase Architectures Derived from Intermolecular Dispersion Interactions.

A systematic series of superbenzene-porphyrin conjugates was synthesized and characterized. All conjugates show a high degree of cluster formation that correlates to the amount of tert-butylated hexa-peri-hexabenzocoronenes (tBuHBCs) attached to the porphyrin's periphery. Determined by mass spectrometry and X-ray diffraction, van der Waals (vdW) interactions like London dispersions (LD), stemming from solubilizing tert-butyl groups, were identified to be the major reason for the cluster formation. Cluster sizes comprised of more than twenty molecules with masses up to 70 000 Da were observed, which are rare examples of large architectures based on synthetic functional molecules, assembled by dispersion interactions. Novel strategies towards the design of solution processable functional materials, capable of dynamic transformations based on non-covalent synthesis can be envisioned.

Surface Pond Energy Absorption Across Four Himalayan Glaciers Accounts for 1/8 of Total Catchment Ice Loss.

Glaciers in High Mountain Asia, many of which exhibit surface debris, contain the largest volume of ice outside of the polar regions. Many contain supraglacial pond networks that enhance melt rates locally, but no large-scale assessment of their impact on melt rates exists. Here we use surface energy balance modeling forced using locally measured meteorological data and monthly satellite-derived pond distributions to estimate the total melt enhancement for the four main glaciers within the 400-km2 Langtang catchment, Nepal, for a 6-month period in 2014. Ponds account for 0.20 ± 0.03 m/year of surface melt, representing a local melt enhancement of a factor of 14 ± 3 compared with the debris-covered area, and equivalent to 12.5 ± 2.0% of total catchment ice loss. Given the prevalence of supraglacial ponds across the region, our results suggest that effective incorporation of melt enhancement by ponds is essential for accurate predictions of future mass balance change in the region.

Isothiazolinones are still widely used in paints purchased in five European countries: a follow-up study.

BACKGROUND: An increasing incidence of contact allergy to methylisothiazolinone (MI) has been seen, caused, in particular, by cosmetic products and paints. A study from 2015 showed that 93.0% of paints bought in five European countries contained MI. New regulations have been discussed for paints in the EU, which may have influenced this market. OBJECTIVES: To re-evaluate the use and concentrations of MI and four other isothiazolinones in water-based wall paints. METHODS: Water-based white wall paints (n = 60) were purchased in retail stores in five European countries: Denmark, France, Germany, Sweden, and the United Kingdom. The paints were analysed for isothiazolione content by the use of high-performance liquid chromatography coupled to ultraviolet detection, and the results were confirmed with high-performance liquid chromatography-tandem mass spectrometry. RESULTS: MI was identified in 55 (91.7%) of the paints, with concentrations ranging from 1.1 to 142.7 ppm. The other isothiazolinones were identified in 20.0% [methylchloroisothiazolinone (MCI)] to 88.3% [benzisothiazolinone (BIT)] of the paints. BIT concentrations varied significantly between countries, whereas MI and MCI concentrations did not. There were no statistically significant differences in MI, MCI and BIT concentrations between the current study and the 2015 study. CONCLUSIONS: MI and other isothiazolinones are widely used in paints available in Europe. Their use does not seem to be decreasing.

Direct Covalent Coupling of Porphyrins to Graphene.

Graphene-porphyrin nanohybrid materials with a direct covalent linkage between the graphene carbon network and the functional porphyrin unit have been successfully synthesized via a one-pot reductive diazotation approach. A graphite-potassium intercalation compound (KC8) was dispersed in THF, and different isolated porphyrin-diazonium salts were added. The direct covalent binding and the detailed characterization of the functional hybrid material were carried out by Raman spectroscopy, TG-MS, UV/vis, and fluorescence spectroscopy. LDI-ToF mass spectrometry was introduced as a new versatile and sensitive tool to investigate covalently functionalized graphene derivatives and to establish the composition of the respective nanohybrid materials.

Dithiafulvenyl-Extended N-Heterotriangulenes and Their Interaction with C60 : Cooperative Fluorescence.

We describe the synthesis as well as the electronic and photophysical characterization of novel N-heterotriangulene derivatives decorated with methoxycarbonyl- and methyl-sulfanyl-substituted dithiafulvenyl moieties. The association of these electron-rich compounds with fullerene C60 as electron acceptor was investigated by means of photophysical, voltammetric, and mass spectrometric methods and rationalized by DFT calculations. Importantly, light-induced interactions between the dithiafulvene-substituted N-heterotriangulene bearing methoxycarbonyl substituents with C60 leads to cooperative fluorescence. Quantitative Job plot analyses by means of fluorescence spectroscopy and voltammetry confirm a 1:1 association with binding constants in the order of 104 m-1 . Supportive results for the supramolecular assembly of both N-heterotriangulenes with C60 were obtained by ESI mass spectrometric investigations in the gas phase.

Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). MEASUREMENTS AND MAIN RESULTS: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

The epidemic of methylisothiazolinone: a European prospective study.

BACKGROUND: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. OBJECTIVES: To describe demographics and MI exposures for European patients with MI contact allergy. METHODS: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000 ppm aq.). RESULTS: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave-on and rinse-off cosmetic products, 24.8% only to leave-on cosmetic products and 38.9% only to rinse-off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms. CONCLUSION: Clinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse-off and leave-on cosmetic products.

Surgery for pressure ulcers in spinal cord-injured patients following a structured treatment programme: a 10-year follow-up.

With the aim to improve the outcomes for spinal cord-injured patients undergoing surgery for pressure ulcers, a structured treatment programme regulating pre- and postoperative care and rehabilitation was introduced in 2002 in Stockholm. Fifty-one consecutive patients operated on between 2002 and 2007 were included in a 10-year follow-up to evaluate the programme regarding initial healing results and long-term ulcer and health status. At one month postoperatively, 49 out of 51 (96%) patients were completely healed. Five patients (5/44, 11%) developed recurrent or new ulcers within 3 years of surgery. Two patients were re-operated on (2/44, 5%). Between 3 and 10 years after surgery, 9 patients (9/33, 27%) had a history of recurrent ulcers, and 6 (6/33, 18%) had a history of new ulcers, a total of 15 patients (15/33, 45%). Of these, three needed re-operation (3/33, 9 %). The health status values using a visual analogue rating scale were 70 (median) at 3 and 10 years compared with 30 (median) preoperatively. The good initial healing, the low ulcer recurrence rate and the raise in health status indicate the value of a structured treatment programme, especially for the first few postoperative years.

Whole-body electromyostimulation to fight sarcopenic obesity in community-dwelling older women at risk. Resultsof the randomized controlled FORMOsA-sarcopenic obesity study.

The effect of whole body-electromyostimulation in community-dwelling women ≥70 with sarcopenic obesity was heterogeneous, with high effects on muscle mass, moderate effects on functional parameters, and minor effects on fat mass. Further, we failed to determine a supportive effect of additional protein-enriched dietary supplementation in this albeit predominately well-nourished group. INTRODUCTION: The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on sarcopenic obesity (SO) in community-dwelling women more than 70 years with sarcopenic obesity. METHODS: Seventy-five community-dwelling women ≥70 years with SO were randomly allocated to either a WB-EMS-application with (WB-EMS &P; 24.9 ± 1.9 kg/m2) or without (WB-EMS; 25.2 ± 1.8 kg/m2) dietary supplementation (150 kcal/day, 56 % protein) or a non-training control group (CG; 24.7 ± 1.4 kg/m2). WB-EMS consisted of one weekly session of 20 min (85 Hz, 350 µs, 4 s of strain-4 s of rest) performed with moderate to high intensity. Primary study endpoint was the Sarcopenia Z-Score constituted by skeletal muscle mass index (SMI, as assessed by dual energy X-ray absorptiometry), grip strength, and gait speed, and secondary study endpoint was body fat (%). RESULTS: Sarcopenia Z-score comparably increases in the WB-EMS and the WB-EMS&P-group (p ≤ .046). Both groups differ significantly (p ≤ .001) from the CG which deteriorated significantly (p = .006). Although body fat changes were most pronounced in the WB-EMS (-0.9 ± 2.1; p = .125) and WB-EMS&P (-1.4 ± 2.5; p = .028), reductions did not statistically differ (p = .746) from the CG (-0.8 ± 2.7; p = .179). Looking behind the covariates, the most prominent changes were determined for SMI, with a significant increase in both EMS-groups (2.0-2.5 %; p ≤ .003) and a decrease in the CG (-1.2 ± 3.1 %; p = .050) with significant between-group differences (p = .001). CONCLUSION: WB-EMS is a safe and attractive method for increasing muscle mass and functional capacity in this cohort of women 70+ with SO; however, the effect on body fat is minor. Protein-enriched supplements did not increase effects of WB-EMS alone.

Three Short Stories about Hexaarylbenzene-Porphyrin Scaffolds.

A feasible two-step synthesis and characterization of a full series of hexaarylbenzene (HAB) substituted porphyrins and tetrabenzoporphyrins is presented. Key steps represent the microwave-assisted porphyrin condensation and the statistical Diels-Alder reaction to the desired HAB-porphyrins. Regarding their applications, they proved to be easily accessible and effective high molecular mass calibrants for (MA)LDI mass spectrometry. The free-base and zinc(II) porphyrin systems, as well as the respective tetrabenzoporphyrins, demonstrate in solid state experiments strong red- and near-infrared-light emission and are potentially interesting for the application in "truly organic" light-emitting devices. Lastly, they represent facile precursors to large polycyclic aromatic hydrocarbon (PAH) substituted porphyrins. We prepared the first tetra-hexa-peri-hexabenzocoronene substituted porphyrin, which represents the largest prepared PAH-porphyrin conjugate to date.

Contact Allergy in Danish Healthcare Workers: A Retrospective Matched Case-control Study.

Contact dermatitis in healthcare workers is a world wide problem. We conducted a retrospective observational study of the patch-test results of 1402 healthcare workers and 1402 matched controls with contact dermatitis who were treated at 3 hospitals departments in Denmark between 2007 and 2014. The primary objective was to determine whether healthcare work was associated with contact allergy to thiuram mix. Unadjusted univariate analyses revealed that healthcare work was significantly associated with occupational contact dermatitis and hand dermatitis. Contact allergy to thiuram mix was more common in healthcare workers was significantly associated with having occupational contact dermatitis, hand dermatitis and older age. In conclusion, we report here a potential problem of contact allergy to thiurams in healthcare workers with contact dermatitis. Legislative authorities may in the future focus on the use of rubber accelerators in, for example, protective gloves, which are widely used by healthcare professionals.