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."

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.

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.

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.

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.

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.

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.

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.

Intergenerational inequities in exposure to climate extremes.

Young generations are severely threatened by climate change.

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.

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.

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.

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.

[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.

Age as a predicting factor in the therapy outcome of multidisciplinary treatment of patients with chronic low back pain--a prospective longitudinal clinical study in 405 patients.

This prospective longitudinal clinical study evaluates the prognostic value of age in the therapy outcome of patients with chronic low back pain treated with a multidisciplinary therapy. Four hundred five patients with chronic low back pain for 3 months or longer and a corresponding sick leave for longer than 6 weeks underwent a 3-week standardized multidisciplinary therapy. Patients were assigned into three groups of age with comparable baseline values at T0. At the 6-month follow-up (T1) five different therapy outcomes were analysed and compared in the three groups: back-to-work status, generic health status (SF36), pain intensity, functional capacity, and satisfaction with the therapy. All three treatment groups improved significantly in all outcome criteria between T0 and T1 except of functional capacity, which did not improve in the older patients. In the total group, the back-to-work rate was 61.7%. At the final follow-up, there were significantly better results in terms of functional capacity and pain level in younger patients, whereas back-to-work rate and satisfaction with therapy did not show a significant difference between the groups analysed. According to the results of this study, older patients with chronic low back pain also derive significant benefit from a multidisciplinary treatment strategy, although in some outcome criteria results were inferior to those obtained in younger patients.

Anterior cruciate ligament reconstruction with quadrupled semitendinosus tendon - minimum 6 year clinical and radiological follow-up.

This clinical study evaluates the minimum 6 year follow-up clinical, functional, radiological and isometric results after arthroscopic reconstruction of the anterior cruciate ligament (ACL) with quadrupled semitendinosus tendon autograft (femoral endobutton and tibial suture disc fixation). Seventy out of 85 operated patients (lost to follow-up 17%) with an average age of 34.3 years could be clinically examined at a mean follow-up time of 6 years and 4 months after surgery. Results revealed a high subjective satisfaction rate of 93%. The preoperative activity level could be maintained in 71% of the patients. The Lysholm score showed very good and good results in 85% with a mean of 83.6%. Normal or nearly normal results on the IKDC score were reported in 85% of the patients. The KT-1000 arthrometer stability testing showed a difference of less than 3 mm compared to the contralateral knee in 75% of the patients. Five patients (7%) had a graft failure during follow-up time. There were no or only mild degenerative changes at the radiographic evaluation in 85% of the patients. In 15% of the patients a femoral and in 40% a tibial tunnel widening of more than 50% was observed, however without a relevance for the clinical and functional status. Midterm results obtained in this study after arthroscopic ACL reconstruction with the quadrupled semitendinosus tendon confirm the outcomes in the literature after shorter follow-up periods that provide very good and good subjective, functional and stability results in about 80-85% of the patients. This surgical technique can be recommended for the active patient with ACL deficiency. However, patients must be informed that activity level cannot always be maintained and a failure rate of 5-10% must be taken into account in the longer term when decision for surgery is made.

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.

The course of high-sensitive C-reactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain - a 6 months prospective longitudinal study.

In this prospective longitudinal study with a follow-up of 6 months, the course of serum concentration of C-reactive protein was measured by an ultrasensitive immunoassay in 31 patients with acute lumbosciatic pain and 41 patients with chronic low back pain. High-sensitive CRP (hsCRP), pain and clinical function were assessed at ten fixed time-points during follow-up. The course of hsCRP values was assessed in relation to the course of pain and clinical function adjusting for possible confounding factors. At the beginning of the study, there were no statistically significant differences in mean hsCRP levels in patients with acute lumbosciatic pain (1.49mg/l) compared to the levels obtained in patients with chronic low back pain (1.30mg/l) and those in a control group from the general population (1.26mg/l). In patients with acute lumbosciatic pain, hsCRP declined significantly in the initial period of 3 weeks with a corresponding decrease in pain and improvement in function and clinical evaluation as assessed with the straight leg raising test (SLR), whereas after this period, the course of the hsCRP did not correspond with the clinical parameters. In patients with chronic low back pain, hsCRP remained approximately constant throughout the whole period with no correlation with pain or function. As a conclusion, according to this study levels of hsCRP do not have a major clinical relevance when evaluating the long-term course of patients with acute lumbosciatic pain and chronic low back pain and therefore should not be taken into primary consideration when decisions on therapy are made.