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.

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.

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.

Words matter: The role of family weight talk in anxiety and depression.

Family weight talk, in the forms of both family weight teasing and encouragement to diet, has been linked to numerous adverse outcomes, including increased disordered eating, unhealthy weight control behaviors, and body mass index. However, little is known about its role in mental health outcomes, especially for emerging adults. Utilizing structural equation modeling, we examined the role of family weight teasing (FWT) and parental encouragement to diet in anxiety and depression and explored body weight perception as a moderator within a sample of 292 emerging adults. Results indicated that FWT was significantly associated with increased anxiety and depression. No significant relationships were found between parental encouragement to diet and the outcome variables, and no group differences emerged across body weight perception. Findings of this pilot study can be used to inform future research to decrease family weight talk and improve psychosocial outcomes for emerging adults.

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.

Soft monolithic infrared neural interface for simultaneous neurostimulation and electrophysiology.

Controlling neuronal activity using implantable neural interfaces constitutes an important tool to understand and develop novel strategies against brain diseases. Infrared neurostimulation is a promising alternative to optogenetics for controlling the neuronal circuitry with high spatial resolution. However, bi-directional interfaces capable of simultaneously delivering infrared light and recording electrical signals from the brain with minimal inflammation have not yet been reported. Here, we have developed a soft fibre-based device using high-performance polymers which are >100-fold softer than conventional silica glass used in standard optical fibres. The developed implant is capable of stimulating the brain activity in localized cortical domains by delivering laser pulses in the 2 µm spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo from the motor cortex and hippocampus in acute and chronic settings, respectively. Immunohistochemical analysis of the brain tissue indicated insignificant inflammatory response to the infrared pulses while the signal-to-noise ratio of recordings still remained high. Our neural interface constitutes a step forward in expanding infrared neurostimulation as a versatile approach for fundamental research and clinically translatable therapies.

Neuroimaging is the new "spatial omic": multi-omic approaches to neuro-inflammation and immuno-thrombosis in acute ischemic stroke.

Ischemic stroke (IS) is the leading cause of acquired disability and the second leading cause of dementia and mortality. Current treatments for IS are primarily focused on revascularization of the occluded artery. However, only 10% of patients are eligible for revascularization and 50% of revascularized patients remain disabled at 3 months. Accumulating evidence highlight the prognostic significance of the neuro- and thrombo-inflammatory response after IS. However, several randomized trials of promising immunosuppressive or immunomodulatory drugs failed to show positive results. Insufficient understanding of inter-patient variability in the cellular, functional, and spatial organization of the inflammatory response to IS likely contributed to the failure to translate preclinical findings into successful clinical trials. The inflammatory response to IS involves complex interactions between neuronal, glial, and immune cell subsets across multiple immunological compartments, including the blood-brain barrier, the meningeal lymphatic vessels, the choroid plexus, and the skull bone marrow. Here, we review the neuro- and thrombo-inflammatory responses to IS. We discuss how clinical imaging and single-cell omic technologies have refined our understanding of the spatial organization of pathobiological processes driving clinical outcomes in patients with an IS. We also introduce recent developments in machine learning statistical methods for the integration of multi-omic data (biological and radiological) to identify patient-specific inflammatory states predictive of IS clinical outcomes.

Occurrence of glycidyl esters in infant formula products on the Canadian market between 2015 and 2019.

Glycidyl fatty acid esters (GEs) are processing contaminants formed during refining steps of vegetable oils. 'In vivo' hydrolysis of GEs releases potentially carcinogenic and genotoxic glycidol (2,3-epoxy-1-propanol). Occurrence of GEs in vegetable oils used for infant formula manufacturing may pose a potential health concern for formula-fed infants. Refined oils are commonly used as the main fat ingredient in formula manufacturing. For this study, different infant formula products (powders, concentrates and ready-to-feed formula products) were purchased and analysed in 2015 (35 samples) and 2019 (33 samples). Seven individual GEs were analysed by LC-MS/MS via direct approach by stable isotope dilution analysis, and total bound glycidol concentrations were calculated. Concentrations of bound glycidol in reconstituted formula reached maxima of 40.3 ng/g in the 2015 samples and 31.5 ng/g in the samples collected in 2019, with respective means of 8.7 ng/g and 6.7 ng/g. The analysed bound glycidol concentrations are comparable with concentration ranges from other studies, but are higher than observed in studies from the European market. Temporal trend data show a reduction of bound glycidol concentrations in 2019. GE concentrations were compared across different manufacturers.

Occurrence of 2- and 3-monochloropropanediol esters (MCPDE) in infant formula products on the Canadian market between 2015 and 2019.

2- and 3-monochloropropanediol esters (MCPDEs) are most commonly formed as process-induced contaminants during the refinement of vegetable oils used for food production. 'In vivo' hydrolysis of 3-MCPDEs releases the potential carcinogen 3-monochloropropanediol (3-MCPD). Levels of MCPDEs in infant formula are of particular concern, as refined oils are commonly used as main fat ingredients. For this study, infant formula samples (powders, liquid concentrates and ready-to-feed infant formula samples) from the Canadian market were purchased and analysed in 2015 (35 samples) and 2019 (33 samples). MCPDE concentrations (expressed as free MCPD equivalents) were examined through an indirect analytical approach, applying acid-catalysed ester cleavage and using cyclohexanone as derivatising agent. Labelled diesters were used as internal standards. 2015 Survey data were analysed by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode (SIM). 2019 Survey data were analysed with an updated method using GC-MS/MS in multiple reaction monitoring modes (MRM). In 2015, levels in reconstituted formula ranging from 3.7 ng/g to 111 ng/g for 3-MCPD and 2.2 ng/g to 56.2 ng/g for 2-MCPD were found. In 2019, levels ranging from 3.9 ng/g to 74.8 ng/g for 3-MCPD and 1.0 ng/g to 33.9 ng/g for 2-MCPD were found. A significantly reduced mean of combined MCPDEs was observed between 2015 and 2019 data (64.5 ng/g, standard deviation (SD) 8.6 ng/g in 2015 to 31.8 ng/g, SD 5.6 ng/g in 2019, p-value = 0.024). For the majority of manufacturers, the data comparison among brand products over time shows decreased levels of MCPDEs. Occurrence data of MCPDEs, including data from previously published surveys (2012/2013), were also compared and a temporal trend was established.

Highlighting uncertainty in clinical risk prediction using a model of emergency laparotomy mortality risk.

Clinical prediction models typically make point estimates of risk. However, values of key variables are often missing during model development or at prediction time, meaning that the point estimates mask significant uncertainty and can lead to over-confident decision making. We present a model of mortality risk in emergency laparotomy which instead presents a distribution of predicted risks, highlighting the uncertainty over the risk of death with an intuitive visualisation. We developed and validated our model using data from 127134 emergency laparotomies from patients in England and Wales during 2013-2019. We captured the uncertainty arising from missing data using multiple imputation, allowing prospective, patient-specific imputation for variables that were frequently missing. Prospective imputation allows early prognostication in patients where these variables are not yet measured, accounting for the additional uncertainty this induces. Our model showed good discrimination and calibration (95% confidence intervals: Brier score 0.071-0.078, C statistic 0.859-0.873, calibration error 0.031-0.059) on unseen data from 37 hospitals, consistently improving upon the current gold-standard model. The dispersion of the predicted risks varied significantly between patients and increased where prospective imputation occurred. We present a case study that illustrates the potential impact of uncertainty quantification on clinical decision making. Our model improves mortality risk prediction in emergency laparotomy and has the potential to inform decision-makers and assist discussions with patients and their families. Our analysis code was robustly developed and is publicly available for easy replication of our study and adaptation to predicting other outcomes.

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.

Orodispersible Films: A Delivery Platform for Solid Lipid Nanoparticles?

To overcome the poor bioavailability observed for many newly developed active pharmaceutical ingredients (APIs), an appropriate formulation strategy is necessary. One approach is the formulation of these substances in solid lipid nanoparticles and their further processing into solid dosage forms. A promising and innovative oral delivery platform could be orodispersible films (ODFs). ODFs were already investigated more closely, e.g., for the administration of API nanoparticles, and proved their suitability for this formulation approach. The current study was aimed at investigating if the HPMC (hydroxypropyl methyl cellulose) film matrix is also suitable to serve as an appropriate delivery platform for solid lipid nanoparticles. Dependent on the type of triglyceride nanoparticles embedded in the film matrix and the formulation of the lipid particles, lipid contents of up to 54 wt.% could be realized in the film matrix without the loss of the nanoparticulate state. Good mechanical properties were confirmed for these films by determining the tensile strength as well as the elongation before breakage. Interestingly, processing of a lipid suspension into this solid dosage form led to a significantly reduced transformation of the lipid particles from the metastable α- into the stable ß-polymorph. This could prove very beneficial when the lipid particles are loaded with APIs.

Stoichiometry-Controlled Reversible Lithiation Capacity in Nanostructured Silicon Nitrides Enabled by in Situ Conversion Reaction.

In modern Li-based batteries, alloying anode materials have the potential to drastically improve the volumetric and specific energy storage capacity. For the past decade silicon has been viewed as a "Holy Grail" among these materials; however, severe stability issues limit its potential. Herein, we present amorphous substoichiometric silicon nitride (SiNx) as a convertible anode material, which allows overcoming the stability challenges associated with common alloying materials. Such material can be synthesized in a form of nanoparticles with seamlessly tunable chemical composition and particle size and, therefore, be used for the preparation of anodes for Li-based batteries directly through conventional slurry processing. Such SiNx materials were found to be capable of delivering high capacity that is controlled by the initial chemical composition of the nanoparticles. They exhibit an exceptional cycling stability, largely maintaining structural integrity of the nanoparticles and the complete electrodes, thus delivering stable electrochemical performance over the course of 1000 charge/discharge cycles. Such stability is achieved through the in situ conversion reaction, which was herein unambiguously confirmed by pair distribution function analysis of cycled SiNx nanoparticles revealing that active silicon domains and a stabilizing Li2SiN2 phase are formed in situ during the initial lithiation.

Multi-year observations of the high mountain water cycle in the Langtang catchment, Central Himalaya.

The Langtang catchment is a high mountain, third order catchment in the Gandaki basin in the Central Himalaya (28.2°N, 85.5°E), that eventually drains into the Ganges. The catchment spans an elevation range from 1400 to 7234 m a.s.l. and approximately one quarter of the area is glacierized. Numerous research projects have been conducted in the valley during the last four decades, with a strong focus on the cryospheric components of the catchment water balance. Since 2012 multiple weather stations and discharge stations provide measurements of atmospheric and hydrologic variables. Full weather stations are used to monitor at an hourly resolution all four radiation components (incoming and outgoing shortwave and longwave radiation; SWin/out and LWin/out), air temperature, humidity, wind speed and direction, and precipitation, and cover an elevational range of 3862-5330 m a.s.l. Air temperature and precipitation are monitored along elevation gradients for investigations of the spatial variability of the high mountain meteorology. Dedicated point-scale observations of snow cover, depth and water equivalent as well as ice loss have been carried out over multiple years and complement the observations of the water cycle. All data presented is openly available in a database and will be updated annually.