Cell wall-mediated maternal control of apical-basal patterning of the kelp Undaria pinnatifida.

The role of maternal tissue in embryogenesis remains enigmatic in many complex organisms. Here, we investigate the contribution of maternal tissue to apical-basal patterning in the kelp embryo. Focussing on Undaria pinnatifida, we studied the effects of detachment from the maternal tissue using microsurgery, staining of cell wall modifications, morphometric measurements, flow cytometry, genotyping and a modified kelp fertilisation protocol synchronising kelp embryogenesis. Detached embryos are rounder and often show aberrant morphologies. When a part of the oogonial cell wall remains attached to the zygote, the apical-basal patterning is rescued. Furthermore, the absence of contact with maternal tissue increases parthenogenesis, highlighting the critical role of maternal signals in the initial stages of development. These results show a key role for the connection to the maternal oogonial cell wall in apical-basal patterning in kelps. This observation is reminiscent of another brown alga, Fucus, where the cell wall directs the cell fate. Our findings suggest a conserved mechanism across phylogenetically distant oogamous lineages, where localised secretion of sulphated F2 fucans mediates the establishment of the apical-basal polarity. In this model, the maternal oogonial cell wall mediates basal cell fate determination by providing an extrinsic patterning cue to the future kelp embryo.

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.

Contact allergy to neomycin in consecutively patch tested Danish eczema patients from 2000 to 2023: A cross-sectional study.

BACKGROUND: Neomycin is an aminoglycoside antibiotic that may cause contact allergy. It was withdrawn as a medicine for human use in Denmark in October 2009 but is still found in some vaccines. OBJECTIVES: To identify time trends in contact allergy to neomycin in the period from 2000 to 2023. METHODS: A cross-section study of patients ≥18 years consecutively patch-tested with neomycin sulfate (20% in pet.) at Gentofte Hospital, Denmark, during the period 2000-2023 was conducted. RESULTS: The overall prevalence of contact allergy to neomycin was 1.4%. The prevalence was significantly lower in the period '2010-2023' (1.2%) than in '2000-2009' (1.8%) (p < 0.005). Contact allergy to neomycin was significantly positively associated with facial dermatitis and age >40 years, and significantly negatively associated with occupational dermatitis and hand dermatitis. No changes in sex, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, or age > 40/≤40 (the MOAHLFA-index) were identified when comparing neomycin contact allergic-patients in the two periods '2010-2023' and '2001-2009'. CONCLUSION: Neomycin is a rare cause of contact allergy in Denmark with a significantly lower prevalence following its withdrawal as a medicinal product for human use in Denmark in 2009.

Contents of sensitising rubber accelerators in disposable rubber gloves: A Copenhagen market survey.

BACKGROUND: Rubber gloves contain rubber accelerators that may cause contact allergy. The content of sensitising rubber accelerators in contemporary rubber gloves is not well known. OBJECTIVES: Identify and quantify the content of rubber accelerators in disposable rubber gloves. METHODS: Fifty-one gloves of 49 different brands were collected. Forty-eight of the gloves were disposable and three re-usable. The gloves were analysed for their content of sensitising rubber accelerators, that is, zinc dithiocarbamates, thiurams, thiazoles/benzothiazoles, diphenylguanidine, and thioureas by high-performance liquid chromatography. RESULTS: Rubber accelerators were identified in 43/48 (90%) of the disposable gloves. In total, 39 gloves contained zinc dibutyldithiocarbamate (ZDBC) (0.18-1.96 mg/g), 34 zinc diethyldithiocarbamate (ZDEC) (0.032-2.78 mg/g), three zinc dibenzyldithiocarbamate (0.65-1.4 mg/g), one zinc dimethyldithiocarbamate (0.23 mg/g), and one 1,3-diphenylguanidine (0.21 mg/g). 2-cyanoethyl dimethyldithiocarbamate (CEDMC) was identified in three gloves (<0.052 mg/g). The one glove labelled as accelerator free contained ZDBC (1.07 mg/g). Only few glove packages had the specific content of rubber accelerators labelled. CONCLUSIONS: The most frequent rubber accelerators in rubber gloves are ZDEC and ZDBC. Accelerator-free gloves may contain rubber accelerators. Full labelling of rubber gloves is needed and producers should be sure not to falsely claim that the rubber gloves are free of rubber accelerators.

Cross-reactivity between thiuram disulfides and dithiocarbamates. A study of TETD and ZDEC using mouse models.

BACKGROUND: Rubber accelerators are used in the vulcanization of rubber. However, rubber accelerators for example tetraethylthiuram disulfide (TETD) and zinc diethyldithiocarbamate (ZDEC) may cause contact allergy. Concomitant reactions between ZDEC and TETD have been observed in patients which could be explained by co- or cross-reactivity. OBJECTIVES: To investigate cross-reactivity between TETD and ZDEC and vice versa. METHODS: Groups of mice were sensitized with TETD or ZDEC based on reported EC3-values. Proliferation of lymphocytes were measured on day 5. To test cross-reactivity, mice were sensitized and challenged 3 weeks later with TETD or ZDEC. The inflammatory response was measured by changes in ear thickness and the proliferative response in CD4+ and CD8+ T cells in the submandibular and cervical draining lymph nodes. RESULTS: Sensitization of mice with doses of ZDEC 3%, TETD 5.6% or TETD 16.2% induced significant increased ear thickness and proliferation of CD4+ and CD8+ T cells. Challenge with ZDEC or TETD in these groups induced significant increased ear thickness. Challenge with ZDEC in mice sensitized to TETD 5.6% or TETD 16.2% induced significant increased proliferation of CD4+ and CD8+ T cells. CONCLUSIONS: We show cross-reactivity between TETD and ZDEC. Patients sensitized to TETD or ZDEC should avoid exposure to both ZDEC and TETD.

Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

BACKGROUND: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). OBJECTIVE: To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. METHODS: A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. RESULTS: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. CONCLUSION: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

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.