Incontinentia pigmenti Stage 1 is not simply vesiculo-bullous but vesiculo-pustular.

Incontinentia pigmenti (IP) is a rare X-linked dominant, male-lethal disorder characterized by pathognomic skin lesions. As described in the literature the typical cutaneous changes follow the pattern of Blaschko's lines and develop in four stages that usually start at birth. Stage 1 is called vesicular, bullous or inflammatory. The vesicles are rapidly filled with eosinophils and thus turn into pustules. Thus, the term "pustular" is relevant to the first phase of IP, and the stage can be considered as "vesiculopustular/inflammatory" to be more precise than "vesicular" or "bullous."

Trophic amplification: A model intercomparison of climate driven changes in marine food webs.

Marine animal biomass is expected to decrease in the 21st century due to climate driven changes in ocean environmental conditions. Previous studies suggest that the magnitude of the decline in primary production on apex predators could be amplified through the trophodynamics of marine food webs, leading to larger decreases in the biomass of predators relative to the decrease in primary production, a mechanism called trophic amplification. We compared relative changes in producer and consumer biomass or production in the global ocean to assess the extent of trophic amplification. We used simulations from nine marine ecosystem models (MEMs) from the Fisheries and Marine Ecosystem Models Intercomparison Project forced by two Earth System Models under the high greenhouse gas emissions Shared Socioeconomic Pathways (SSP5-8.5) and a scenario of no fishing. Globally, total consumer biomass is projected to decrease by 16.7 ± 9.5% more than net primary production (NPP) by 2090-2099 relative to 1995-2014, with substantial variations among MEMs and regions. Total consumer biomass is projected to decrease almost everywhere in the ocean (80% of the world's oceans) in the model ensemble. In 40% of the world's oceans, consumer biomass was projected to decrease more than NPP. Additionally, in another 36% of the world's oceans consumer biomass is expected to decrease even as projected NPP increases. By analysing the biomass response within food webs in available MEMs, we found that model parameters and structures contributed to more complex responses than a consistent amplification of climate impacts of higher trophic levels. Our study provides additional insights into the ecological mechanisms that will impact marine ecosystems, thereby informing model and scenario development.

Next-generation ensemble projections reveal higher climate risks for marine ecosystems.

Projections of climate change impacts on marine ecosystems have revealed long-term declines in global marine animal biomass and unevenly distributed impacts on fisheries. Here we apply an enhanced suite of global marine ecosystem models from the Fisheries and Marine Ecosystem Model Intercomparison Project (Fish-MIP), forced by new-generation Earth system model outputs from Phase 6 of the Coupled Model Intercomparison Project (CMIP6), to provide insights into how projected climate change will affect future ocean ecosystems. Compared with the previous generation CMIP5-forced Fish-MIP ensemble, the new ensemble ecosystem simulations show a greater decline in mean global ocean animal biomass under both strong-mitigation and high-emissions scenarios due to elevated warming, despite greater uncertainty in net primary production in the high-emissions scenario. Regional shifts in the direction of biomass changes highlight the continued and urgent need to reduce uncertainty in the projected responses of marine ecosystems to climate change to help support adaptation planning.

Intergenerational inequities in exposure to climate extremes.

Young generations are severely threatened by climate change.

Comparing the effects of proactive treatment with tacrolimus ointment and mometasone furoate on the epidermal barrier structure and ceramide levels of patients with atopic dermatitis.

BACKGROUND: The epidermal skin barrier and lipids that are integral to its structure are impaired in atopic dermatitis (AD). Current treatment guidelines include proactive therapy. OBJECTIVE: This study assessed the effect of 12 weeks of proactive treatment with tacrolimus ointment 0.1% (TAC) compared with mometasone furoate cream (MF) on specific skin barrier lipids in patients with AD who previously received 10 days of reactive treatment with either agent. METHODS: This was an open-label, non-interventional study. In the reactive phase, forearm lesions in 20 patients were treated with either TAC or MF twice daily for 10 days. In the subsequent proactive phase, patients applied TAC or MF twice weekly for 12 weeks (n = 16 patients). RESULTS: Over the 12-week proactive treatment period, the mean local SCORAD significantly decreased in the TAC and MF treatment group. Levels of total and individual ceramides increased in both groups. Normalized intercellular lipid lamellae values were significantly higher with proactive TAC treatment than MF and undistinguishable from healthy skin. CONCLUSION: The results show that proactive treatment with TAC is superior in restoring the skin barrier.

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, or chronically relapsing, inflammatory skin disease associated with asthma and allergic rhinitis, and is dominated by Th2 cells. The co-stimulatory T-cell receptor OX40 and its ligand, OX40L, play a central role in the pathogenesis of AD, as their interactions are crucial for the generation of TH2 memory cells. Using enzyme-linked immunoassay (ELISA) and flow cytometry on blood samples from patients with AD and healthy volunteers, this study shows that the serum level of soluble (s) OX40 is decreased in patients with AD, and the expression of OX40 by activated skin-homing CD4+ T cells is increased. This study further shows, using immunofluorescence on skin biopsies, that OX40+ and OX40L+ cells are co-located within the dermis, indicating local activity of OX40/OX40L. Serum levels of sOX40 were associated with atopic diseases and, together, these results support that the OX40 system is important for chronic inflammation in AD skin.

Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change.

While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (±4% SD) under low emissions and 17% (±11% SD) under high emissions by 2100, with an average 5% decline for every 1 °C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.

State-of-the-art global models underestimate impacts from climate extremes.

Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.

[S2k-Guideline on Meniscal Disease: Non-operative and Surgical Management]. / S2k-Leitlinie Meniskuserkrankung: konservative und operative Therapie.

A meniscal injury should not automatically lead to surgery. Even in light of all the developments in arthroscopic surgery, non-operative management still has a place in the treatment algorithms for lesions around the knee. In this second publication of the German guidelines for meniscal surgery, the authors describe the various treatment possibilities, their indications and offer critical insight into the various therapeutic options. This will allow the patient and physician alike to make the proper individual decisions. Various German speaking associations addressing topics surrounding the knee have joined forces to develop these guidelines for meniscal lesions. The hope is that these two publications on the topic will shed light on the ongoing debate and offer some guidance.

Linked sustainability challenges and trade-offs among fisheries, aquaculture and agriculture.

Fisheries and aquaculture make a crucial contribution to global food security, nutrition and livelihoods. However, the UN Sustainable Development Goals separate marine and terrestrial food production sectors and ecosystems. To sustainably meet increasing global demands for fish, the interlinkages among goals within and across fisheries, aquaculture and agriculture sectors must be recognized and addressed along with their changing nature. Here, we assess and highlight development challenges for fisheries-dependent countries based on analyses of interactions and trade-offs between goals focusing on food, biodiversity and climate change. We demonstrate that some countries are likely to face double jeopardies in both fisheries and agriculture sectors under climate change. The strategies to mitigate these risks will be context-dependent, and will need to directly address the trade-offs among Sustainable Development Goals, such as halting biodiversity loss and reducing poverty. Countries with low adaptive capacity but increasing demand for food require greater support and capacity building to transition towards reconciling trade-offs. Necessary actions are context-dependent and include effective governance, improved management and conservation, maximizing societal and environmental benefits from trade, increased equitability of distribution and innovation in food production, including continued development of low input and low impact aquaculture.

Birch pollen influence the severity of atopic eczema - prospective clinical cohort pilot study and ex vivo penetration study.

There is little clinical evidence for a correlation between the severity of atopic eczema (AE) and pollen exposition. To obtain more data, we performed a clinical cohort pilot study about the influence of pollen on AE between sensitized and nonsensitized subjects and an experimental study addressing the cutaneous penetration of pollen into the skin. Fifty-five patients were monitored during birch pollen season. To study the cutaneous penetration, grass pollen allergens were applied on excised skin and the uptake in CD1c-expressing dendritic cells was investigated. The correlation between environmental pollen load and severity of the Scoring Atopic Dermatitis (SCORAD) score and pruritus was observed, regardless of the status of sensitization. The sensitized group recovered significantly worse after the birch pollen season. Remarkably higher amounts of pollen allergens taken up by CD1c cells were detected in epidermal cells derived from skin explants with a disturbed epidermal barrier. These findings suggest an exacerbating role of pollen in AE utilizing the epidermal route.

Malassezia spp.-specific immunoglobulin E level is a marker for severity of atopic dermatitis in adults.

The significance of allergen-specific IgE as marker for severity of atopic dermatitis is controversial. The aim of this study was to determine the frequency of IgE-mediated sensitisation to food and environmental allergens in 132 children and 67 adults with atopic dermatitis, and its correlation to severity of atopic dermatitis (SCORAD). Total IgE was elevated (> 100 kU/l) in 79.7% of adults and 46.8% of children. Sensitisation frequencies to allergens, particularly microbial allergens, were up to 10-fold higher in adults compared to children. Severity of atopic dermatitis correlated with elevated total IgE in adults (r = 0.549, p < 0.001) and children (r = 0.344, p = 0.005) and with Malassezia spp.-specific IgE in adults (r = 0.429, p = 0.007). Total IgE is a marker for severe atopic dermatitis in both age groups. Malassezia spp.-specific IgE is an important allergen-specific marker for severity of atopic dermatitis in adults.

Comparison of effects of tacrolimus ointment and mometasone furoate cream on the epidermal barrier of patients with atopic dermatitis.

BACKGROUND: The skin barrier plays a crucial role in the pathophysiology of atopic dermatitis. The quality of the skin barrier can be assessed using a new semi-quantitative method to measure intercellular lipid lamellae. This procedure was used to evaluate the influence of the topical application of the calcineurin inhibitor tacrolimus 0.1% ointment (Protopic®) versus mometasone furoate cream (Ecural®) on the quality of the skin barrier. PATIENTS AND METHODS: 20 adult patients with active atopic dermatitis (SCORAD 10-63) were included in an open, non-interventional study. Lesions on their forearms were treated twice daily over 10 days with either tacrolimus 0.1% ointment or mometasone furoate cream. At the beginning and the end of the treatment period, SCORAD, TEWL and skin hydration were determined and the intercellular lipids were measured using transmission electron microscopy. RESULTS: The SCORAD improved in both groups nearly to the same extent, whereas TEWL and skin hydration improved significantly only in the tacrolimus group. Using the semi-quantitative analysis of intercellular lipid length per 1,000 nm(2) intercellular space, a twofold increase for mometasone furoate cream and a fourfold increase for tacrolimus 0.1% ointment were determined. CONCLUSIONS: In addition to its known antiinflammatory effect, tacrolimus 0.1% ointment leads also to a measurable increase of the lipids of the skin barrier in patients with atopic dermatitis, exceeding the effect of mometasone furoate cream.

Long-term outcome of anterior cruciate ligament reconstruction with an autologous four-strand semitendinosus tendon autograft.

PURPOSE: Although the short- and mid-term outcomes of ACL reconstruction with a hamstring graft are promising, clinical investigations reporting the long-term results after ten years or longer are rare. Therefore we performed a retrospective single-blinded evaluation of ACL reconstruction using a four-stranded single-bundle reconstruction with a semitendinosus tendon graft with extracortical fixation. METHODS/RESULTS: At follow-up patients obtained at least the same level in the clinical outcome scores (Lysholm, IKDC, Tegner) compared to previous studies with a similar follow-up time using a STG graft. Furthermore there was no detectable difference in the incidence of osteoarthritis. Patients having a negative pivot shift test showed significantly fewer signs of radiographic osteoarthritis and better functional assessment scores. CONCLUSION: On the basis of our investigation, we conclude that the reconstruction of the ACL by a quadrupled semitendinosus tendon graft with extracortical anchorage can achieve excellent clinical and subjective results after a follow-up of ten years.

Interferometric measurement of the temperature dependence of an index of refraction: application to fused silica.

The light reflected by an uncoated Fabry-Perot etalon presents dark rings which give a very sensitive measurement of the variations of the return optical path in the etalon. By measuring the diameters of these rings as a function of the etalon temperature T, we get a sensitive measurement of the derivative dn/dT of the index of refraction n. We have made this experiment with a fused silica etalon and we have achieved a 2% relative uncertainty on dn/dT, comparable to the uncertainty of the best experiments.

The role of IL-8 in patients with fibromyalgia: a prospective longitudinal study of 6 months.

OBJECTIVE: In this prospective longitudinal clinical study, we evaluated the role of proinflammatory cytokine IL-8 and its clinical relevance in patients with fibromyalgia (FM) who fulfilled clearly defined inclusion and exclusion criteria and underwent a 3-week inpatients multidisciplinary pain therapy. METHODS: IL-8 in sera was measured in 20 patients with FM and 80 healthy participants at 4 fixed time points: at the beginning of the study, at 10 days, 21 days, and 6 months, respectively. Pain intensity, back function, depression, nicotine/alcohol consumption, and medication were assessed in the patient group and correlated with IL-8 levels. RESULTS: Before and during the inpatient therapy, the serum level of IL-8 was significantly higher in patients with FM compared with controls (P<0.001), but did not correlated with pain intensity and medication. Already at T1 there was a significant reduction of IL-8 serum level (P=0.023) in patient group. Six months after multidisciplinary pain therapy, IL-8 serum level in FM patients was still significantly higher than controls (P=0.044) but reduced approximately to normal range and correlated significantly negatively with pain intensity (r=-0.782, P=0.001). Patients with FM had significantly less pain (P<0.001) and better back function (P<0.001) at day 2 than at day 0. In addition, in patients with FM, IL-8 serum level correlated with nicotine consumption (r=0.471, P=0.042). CONCLUSIONS: Our results suggest that IL-8 level contributes in patients with FM whose pain intensity and back function can be improved under influence of multidisciplinary pain therapy without need of an anti-IL-8 therapy.

Circulating cytokine levels compared to pain in patients with fibromyalgia -- a prospective longitudinal study over 6 months.

OBJECTIVE: This prospective study examined circulating cytokines in patients with fibromyalgia (FM) over 6 months rather than at only one timepoint, and investigated correlations between serum cytokine concentrations and pain intensity in FM patients receiving multidisciplinary pain therapy. METHODS: Serum concentrations of proinflammatory cytokines interleukin 6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) and antiinflammatory cytokines IL-4 and IL-10 were measured (Bio-Plex system) in 20 FM patients and 80 healthy subjects on admission and 10, 21, and 180 days after initiation of treatment and correlated to pain intensity. RESULTS: On admission, serum levels of IL-8 (p < 0.001) and TNF-alpha (p < 0.001), but not IL-6, were elevated in patients with FM. No significant difference in IL-4 and IL-10 was found between FM patients and controls. High IL-8 levels remained consistent during the followup, but TNF-alpha was already reduced after 10 days and until 6 months after therapy. After 6 months' treatment with multidisciplinary pain therapy, IL-8 and TNF-alpha levels were significantly lower than at the beginning (p < 0.05 for IL-8, p < 0.001 for TNF-alpha). IL-8 but not TNF-alpha serum levels were correlated with pain intensity (r = -0.782, p = 0.001) in FM patients after 6 months' multidisciplinary pain therapy. CONCLUSION: Our results suggest that proinflammatory cytokines TNF-alpha and IL-8 are involved in FM, but they do not apparently provoke the pain of FM directly. Multidisciplinary pain therapy modified the cytokine profile in patients with FM during the observation period.

The role of TNF-alpha in patients with chronic low back pain-a prospective comparative longitudinal study.

OBJECTIVES: In this prospective longitudinal clinical study with a matched-pair design, we evaluated the role of tumor necrosis factor-alpha (TNF-alpha) and its clinical relevance in patients with chronic low back pain. METHODS: One hundred twenty patients with chronic low back pain were matched to a healthy control group. Patients and controls were prospectively followed for 6 months. At 4 fixed time points (day 0, day 10, day 20, and 6 mo) blood samples were taken and TNF-alpha levels compared in the 2 groups, and correlations with pain level and clinical function were analyzed. RESULTS: At the beginning and at all other time points, there was a significantly higher proportion of TNF-alpha positive participants in the patients group than in the control group. The proportion of TNF-alpha positive patients decreased during the first 10 days of a multidisciplinary therapy in the patient group, but after this initial period, TNF-alpha levels remained constantly high with no further change until the final follow-up. In the healthy control group, the proportion of participants with positive TNF-alpha levels remained constant throughout the entire period. No significant correlation between TNF-alpha levels and pain or clinical function was detected. DISCUSSION: TNF-alpha seems to have a significant role in patients with chronic low back pain. However, the pathophysiology of this process, the clinical relevance of TNF-alpha and, especially, its part in a potential therapy regimen in these patients need to be more closely examined and defined in additional studies.