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Forest inventories provide reliable evidence-based information to assess the state and development of forests over time. They typically consist of a random sample of plot locations in the forest that are assessed individually by field crews. Due to the high costs of these terrestrial campaigns, remote sensing information available in high quantity and low costs is frequently incorporated in the estimation process in order to reduce inventory costs or improve estimation precision. With respect to this objective, the application of multiphase forest inventory methods (e.g., double- and triple-sampling regression estimators) has proved to be efficient. While these methods have been successfully applied in practice, the availability of open-source software has been rare if not non-existent. The R package forestinventory provides a comprehensive set of global and small area regression estimators for multiphase forest inventories under simple and cluster sampling. The implemented methods have been demonstrated in various scientific studies ranging from small to large scale forest inventories, and can be used for post-stratification, regression and regression within strata. This article gives an extensive review of the mathematical theory of this family of design-based estimators, puts them into a common framework of forest inventory scenarios and demonstrates their application in the R environment.

The German National Forest Inventory consists of a systematic grid of permanent sample plots and provides a reliable evidence-based assessment of the state and the development of Germany’s forests on national and federal state level in a 10 year interval. However, the data have yet been scarcely used for estimation on smaller management levels such as forest districts due to insufficient sample sizes within the area of interests and the implied large estimation errors. In this study, we present a double-sampling extension to the existing German National Forest Inventory (NFI) that allows for the application of recently developed design-based small area regression estimators. We illustrate the implementation of the estimation procedure and evaluate its potential for future large-scale operational application by the example of timber volume estimation on two small-scale management levels (45 and 405 forest district units respectively) over the entire area of the federal German state of Rhineland-Palatinate. An airborne laserscanning (ALS) derived canopy height model and a tree species classification map based on satellite data were used as auxiliary data in an ordinary least square regression model to produce the timber volume predictions. The results support that the suggested double-sampling procedure can substantially increase estimation precision on both management levels: the two-phase estimators were able to reduce the variance of the one-phase simple random sampling estimator by 43% and 25% on average for the two management levels respectively.

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Determining the exact position of a forest inventory plot—and hence the position of the sampled trees—is often hampered by a poor Global Navigation Satellite System (GNSS) signal quality beneath the forest canopy. Inaccurate geo-references hamper the performance of models that aim to retrieve useful information from spatially high remote sensing data (e.g., species classification or timber volume estimation). This restriction is even more severe on the level of individual trees. The objective of this study was to develop a post-processing strategy to improve the positional accuracy of GNSS-measured sample-plot centers and to develop a method to automatically match trees within a terrestrial sample plot to aerial detected trees. We propose a new method which uses a random forest classifier to estimate the matching probability of each terrestrial-reference and aerial detected tree pair, which gives the opportunity to assess the reliability of the results. We investigated 133 sample plots of the Third German National Forest Inventory (BWI, 2011–2012) within the German federal state of Rhineland-Palatinate. For training and objective validation, synthetic forest stands have been modeled using the Waldplaner 2.0 software. Our method has achieved an overall accuracy of 82.7% for co-registration and 89.1% for tree matching. With our method, 60% of the investigated plots could be successfully relocated. The probabilities provided by the algorithm are an objective indicator of the reliability of a specific result which could be incorporated into quantitative models to increase the performance of forest attribute estimations.

Abstract Background Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®. Methods Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing. Results In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels. Conclusions The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis. Trial registration The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.

Abstract Objectives The objective of this study was twofold: to determine the prevalence of arterial and venous thromboembolic events in the Norwegian Hereditary Hemorrhagic Telangiectasia (HHT) population, and to explore potential factors linked to such events, with particular emphasis on FVIII. Methods Patients with an HHT diagnosis attending the Otorhinolaryngology Department at Oslo University Hospital—Rikshospitalet were included consecutively between April 2021 and November 2022. We recorded the participants' medical history with an emphasis on thromboembolic events. Measurements of blood constituents, including FVIII, FIX, vWF, hemoglobin, iron, ferritin, and CRP were performed. Results One hundred and thirty‐four patients were included in the study. The total prevalence of thromboembolic events among the participants was 23.1%. FVIII levels were high (>150 IU/dL) in the majority of HHT patients (n = 84) (68.3%) and were significantly associated with thromboembolic events (p

Abstract Habitat disturbance affects not only the abundance, species richness and species composition of the local fauna, but also the body size of specific individuals and body size patterns in animal assemblages. Particularly large disturbances occur in agroecosystems, where many agricultural treatments are carried out. One of them, which is most commonly applied to grasslands and which significantly damages the habitat structure, is mowing. We examined the effect of mowing on mean, skewness and kurtosis of the body size in epigeic spider assemblages. The research was conducted on mesic meadows in eastern Poland, in an agricultural landscape typical for this region, consisting of a mosaic of meadows, fields and forests. Spiders were collected using pitfall traps in two sampling periods: the first before mowing and the second when part of the meadows had been mown. Mowing had no significant effect on mean body size, skewness and kurtosis of the body size in epigeic spider assemblages. However, after the cut, mown plots showed, on average, significantly smaller spider species than unmown plots. Both the value of skewness and kurtosis significantly increased after mowing but to the same extent on both the control and mown plots. The decrease in mean body size and increase in skewness in spider assemblages were mainly due to an increase in the number of small species from the Linyphiidae family. It is likely that these species began to migrate (via ballooning) during the second sampling session, following the start of haying, and were thus caught in traps more frequently. Our study showed no clear, significant changes in the body size structure of epigeic spiders in mown meadows compared to unmown ones, which may suggest that the mowing, where extensive farming is practised, does not have a long‐term significant negative impact on this group of invertebrates.

Abstract Background The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation. Methods We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations. Results Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260). Conclusion We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes.

Background A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis. Objective This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV). Method ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20–500 ng/mL). Commercially available trigger Ex-tem was compared with modified triggers based on FXa or RVV. Reversibility of apixaban in the samples was studied; CT was measured with and without addition of DOAC-Stop or andexanet alfa, respectively, and the difference in CT was calculated (CTdiff). Results Using FXa as trigger, we detected apixaban concentrations at 20 ng/mL and above with 100% sensitivity and 100% specificity in patient samples and in vitro. Corresponding data for Ex-tem were 92% sensitivity and 100% specificity in patients, and 94% sensitivity and 100% specificity in vitro, and for RVV 97% sensitivity and 94% specificity in patients, and 97% sensitivity and 100% specificity in vitro, respectively. CTdiff data were similar. Patient sample data were obtained within 20 minutes from sampling. Conclusion Apixaban at low therapeutic concentrations was detected within 20 minutes, and with high sensitivity and specificity. A trigger based on FXa outperformed the commercial trigger Ex-tem and a trigger based on RVV. ROTEM with a FXa-based trigger is a promising method to detect apixaban bedside in acute settings.

Serum amyloid P component (SAP) is present in seminal plasma, on spermatozoa, and in different tissues of the male reproductive tract, but its function is not known. The aims of this study were to determine if the concentration of SAP in seminal plasma is associated with commonly assessed semen parameters and to investigate if SAP could be a new, indirect biomarker for these parameters. In a cross-sectional study of 203 young volunteers, the concentration of SAP in seminal plasma was measured with a in-house developed enzyme-linked immunosorbent assay. Scatter plots, Pearson's correlation coefficients (r), and linear regression models were produced, and SAP showed a statistically significant correlation with sperm concentration (r = 0.75), sperm number (r = 0.68), semen volume (r = −0.19), progressive sperm motility (r = 0.24), and sperm immotility (r = −0.20). When the study group was dichotomized, SAP could be used to discriminate samples with a sperm concentration < or ≥5 × 106 ml−1, 15 × 106 ml−1, or 40 × 106 ml−1, and in receiver operating characteristic curves, the corresponding areas under the curves were 0.97, 0.93, and 0.82, respectively, with P < 0.001 for all three cutoff values studied. The concentration of SAP in seminal plasma showed a strong, positive correlation with the concentration of spermatozoa in semen. SAP may be used as a new indirect potential biomarker for sperm concentration in fresh and in frozen, stored samples. In addition, it is envisaged that the assay could be developed into a home fertility test to differentiate between a low and a normal sperm concentration.

BackgroundThe infestation with Echinococcus multilocularis larvae may persist in humans for up to decades without evident clinical symptoms. Longitudinal investigations are needed to understand the dynamic immunological processes in alveolar echinococcosis (AE) patients associated with an active and progressive, a stable or a regressive course of disease.Methodology/principal findingsThis study evaluated the E. multilocularis specific antibody responses, systemic cytokine, and chemokine serum levels over a 10-year follow-up period, as well as cellular responsiveness in AE patients. Our results demonstrate a rapid decrease in antibodies against E. multilocularis specific antigen Em2+. Especially in cured patients, these antibodies remained negative, making them a significant predictor for cured AE. E. multilocularis specific IgG4, and indirect hemagglutination IHA decreased later in time, after around 5 years. While total IgE did not show significant dynamics over the course of disease, E. multilocularis specific IgE decreased after one to two years, and increasing levels were a significant predictor of progressive disease. There was no significant change in systemic IL-8, IL-9, CCL18 or CCL20 serum levels over time. Univariate analysis across groups indicated lower IL-8 levels in cured patients; however, this result could not be confirmed by multivariate analysis. Levels of CCL17 decreased during treatment, especially in cured patients, and thus might serve as a predictive or risk factor for progressive disease. Levels of IL-10 and CCL13 decreased during disease, especially after five and ten years of intervention. The E. multilocularis antigen (EmAg) inducible cellular productions of MCP1(CCL13), TARC(CCL17) and PARC(CCL18) were lowest in patients with cured AE and infection-free controls, while the EmAg inducible cellular production of IFN-γ increased after cure. Significant positive cytokine and chemokine correlations were observed in AE patients for IL-9, IL-10, CCL13(MCP-4), CCL17(TARC) and CCL20(LARC)(for all pConclusions/significanceRepeated biomarker surveys are advisable to evaluate progression or regression of disease during longitudinal follow-up and such analyses can support imaging techniques and improve staging of AE patients.

Abstract Objective Calcitonin is considered to be a biomarker of medullary thyroid carcinoma and C-cell hyperplasia, but calcitonin can also be elevated in about 30% of the patients with end-stage kidney disease. We reported preoperative calcitonin serum levels in 31 patients on hemodialysis before parathyroid surgery, evaluate influencing factors on calcitonin levels and determine postoperative calcitonin levels after parathyroid surgery. Results Median preoperative serum calcitonin was 8 pg/ml (range 2 to 165 pg/ml), serum calcitonin concentration declined postoperatively to 3 pg/ml (range 1 to 192 pg/ml). There was a strong positive correlation between pre- and postoperative serum calcitonin levels (r = 0.92; p > 0.01). Elevated preoperative serum calcitonin concentrations (more than 10 pg/ml) were found in 14 out of 32 dialysis-dependent patients (44%). Preoperative calcitonin levels of male patients were significantly higher than female patients. Hypercalcitoninemia showed a positive correlation to body mass index (p

The “burnout” phenomenon, supposedly caused by work related stress, is a challenge for academic psychiatry both conceptually and professionally. Since the first description of burnout in 1974 until today, more than 140 definitions have been suggested. Burnout–symptomatology's main characteristic, the experience of exhaustion, is unspecific. Different development–models of burnout were proposed, assumed to depict a quasi-natural process. These could not be confirmed empirically. An expert consensus on the diagnostic criteria and the conceptual location, whether as an independent disorder or as a risk, could not be agreed on. Nevertheless, the phenomenon of burnout in the ICD-11 is considered to be categorized as a work-related disorder. Psychiatric research on the burnout–phenomenon ignores problems of definition resulting from different perspectives: It may meet societal expectations, but does not fulfill scientific criteria, and therefore is not suitable to establish an objective diagnosis and treatment. Parallel detection of ICD/DSM diagnoses from an expert perspective and subjective perturbation models are considered appropriate.

BackgroundAlveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes.Methodology/principal findingsWe evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group.Conclusions/significancemAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp.

Abstract Background Colorectal cancer (CRC) is the fourth leading cause of cancer related deaths worldwide and prognosis in advanced tumor stage still remains poor. Since CK1 isoforms have been reported to be deregulated in several tumor entities CK1 has emerged as a novel drug target in cancer therapy. In this study we set out to investigate whether CK1α might have the potential to serve as prognostic marker. Methods CK1α RNA and protein expression levels in healthy and tumor tissue of CRC patients were analyzed using quantitative real-time PCR and Western Blot analysis, respectively. Prognostic relevance was investigated by correlating obtained CK1α expression levels with patients’ survival rate generating Kaplan-Meier survival plots. Results It could be shown that CK1α is overexpressed in colorectal tumor tissue compared to normal tissue and CK1α overexpression in tumor tissue correlates with poor survival in CRC patients. Results become more significant when only considering patients with high-grade tumors, as well as patients assigned to UICC II and UICC III stage. Furthermore, Cox regression analysis revealed that CK1α is an independent prognostic factor. In addition, tumors expressing decreased levels of the kinase reveal positive effects on overall survival when localized in the right colon compared to those in the left side. Conclusion In summary, this study provides evidence for the first time that CK1α RNA levels might serve as prognostic marker for CRC.

Abstract Background Thyroid hemorrhage is considered to be an uncommon complication following blunt trauma to the neck. This condition is potentially life-threatening due to airway compression and may therefore require emergency airway management and surgical intervention in some cases. Case presentation We present the case of a 52-year-old woman who experienced a traumatic thyroid gland rupture (right lobe) with subsequent active arterial bleeding from branches of the inferior thyroid artery. On the same day, the patient presented to our emergency department with a painful swelling of the neck with an inspiratory stridor and hoarseness a few hours after a cycling accident. A right hemithyroidectomy was performed. The postoperative course was uneventful. We identified 33 additional cases published in English literature within the last 30 years, reporting blunt trauma to the neck with hemorrhagic complication of the thyroid gland. We provide a systematic review and particularly consider the aspects of endocrine surgery. Conclusion The treatment approach for patients with blunt thyroid trauma should be dependent on the extent of the thyroid injury. Patients with tracheal compression, active bleeding and increasing hoarseness/shortness of breath require emergency airway control and often surgical exploration for hemorrhage control followed by resection of the ruptured thyroid. Importantly, in contrast to routine thyroid surgery, no electromyographic endotracheal tube is used during emergency intubation. Exchange of an endotracheal tube should be carefully evaluated due to difficult airway management in this setting. For protection against double-sided recurrent nerve palsy and postoperative hypoparathyroidism, a unilateral approach is preferable whenever possible.

Alveolar echinococcosis (AE) is caused by the intermediate stage of Echinococcus multilocularis. We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Echinococcus multilocularis Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of Echinococcus multilocularis (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.

Background. Primary hyperparathyroidism (pHPT) is a common endocrine disorder of the parathyroid glands. In most cases pHPT is caused by single gland disease, but about 10% of patients suffer from sporadic multiglandular disease (MGD). Patients with MGD, especially with ectopic parathyroid adenomas, have an increased risk for persistence/recurrence after surgery. Normally, sporadic MGD cannot be diagnosed preoperatively by parathyroid scintigraphy. We analyzed the potential of positron emission tomography/computed tomography (Met-PET/CT) to predict MGD. Methods and Case Presentation. We reviewed the literature, if preoperative Met-PET/CT could predict MGD in patients with pHPT. Further, we present a 71-year-old female with ectopic MGD. Preoperative localization via Met-PET/CT showed MGD with two areas suspected to be enlarged parathyroid glands (left lateral to the thyroid lobe and posterior mediastinum). Both diagnostic findings were extirpated and parathormone dropped into normal levels. Results. We identified four additional manuscripts, referring to MGD and Met-PET/CT with divergent results. Preoperative localization diagnostics using Met-PET/CT may not necessarily identify MGD. In most cases, Met-PET/CT localized only one adenoma and localizes larger adenomas more reliably than smaller adenomas. Conclusion. Identifying patients at risk of MGD preoperatively remains challenging. We found MET-PET/CT seems to predict MGD in patients with large size and high weight PTH adenomas. For ectopic parathyroid adenomas, accurate preoperative localization is the key to successful surgical removal. Met-PET/CT appears to have great potential in soft-tissue analysis of complex anatomical regions and can predict ectopic parathyroid adenomas.

Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment.We analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy. A broad panel of monoclonal antibodies was used to characterize the lesion by immunohistochemistry. A change in the cellular infiltrate was observed between the different chemotherapy times. During the initial phases of treatment an increase in CD15+ granulocytes and CD68+ histocytes as well as in small particles of Echinococcus multilocularis (spems) was observed in the tissue surrounding the metacestode. Furthermore, we observed an increase in CD4+ T cells, CD20+ B cells and CD38+ plasma cells during a longer duration of treatment.ABZ treatment of AE leads to morphological changes characterized by an initial, predominantly acute, inflammatory response which is gradually replaced by a response of the adaptive immune system.

Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD.This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor (APC-PCI) and by markers of endothelial activation: Factor VIII coagulant activity (FVIII:C) and soluble thrombomodulin (s-TM) at 6-8 time points over three months.Overall, PC, AT and FVIII:C increased in parallel after engraftment. Significant correlations between PC and FVIII:C (r = 0.64-0.82, p

Andreas Hillenbrand1, Manfred Weiss3, Uwe Knippschild1, Hans G Stromeyer1, Doris Henne-Bruns1, Markus Huber-Lang2,† Anna M Wolf1,†1Department of General, Visceral, and Transplantation Surgery, 2Department of Traumatology, Hand and Reconstructive Surgery, 3Department of Anesthesiology, University Hospital of Ulm, Ulm, Germany †These authors contributed equallyPurpose: Intensive care unit patients usually have a deregulated glucose homeostasis and present with hyperglycemia and hyperinsulinemia, suggesting overall insulin resistance. Adiponectin has significant anti-inflammatory and insulin-sensitizing effects and is diminished in morbidly obese and in critically ill patients. Reduced adiponectin could contribute to insulin resistance in these patients. We examined how far insulin demand in critically ill patients is correlated with patient adiponectin levels.Patients and methods: Adiponectin, resistin, leptin, insulin demand, minimal and maximal blood sugar levels, epinephrine, and hydrocortisone demand were measured 1 day after diagnosis of severe sepsis or septic shock in 25 patients (8 female, 17 male; median age 65 years; range: 31 to 87 years).Results: Insulin demand (range: 0–8 IU/h; median 3.5 IU) was positively correlated with serum adiponectin levels (median: 10.1 µg/mL; range: 2.9–47.6 µg/mL; r = +0.56, P < 0.01). There was no significant correlation between insulin demand and leptin serum levels (median: 18.1 ng/mL; range: 0.3–80.7 ng/mL; r = +0.29, P = 0.08) or resistin serum levels (median: 103.9 ng/mL; range: 14.7–352.3 ng/mL; r = +0.13, P = 0.27). Epinephrine demand (median: 0.08 µg/kg*min; range: 0.02–0.63 µg/kg*min) was negatively correlated with male adiponectin levels (r = -0.58; P < 0.01; females: r = -0.36; P = 0.19) and positively correlated with resistin levels (r = 0.43; P = 0.02). Patient body mass index (median 26 kg/m²; range: 18–37) was positively correlated with serum leptin (r = 0.60; P < 0.01) but was not correlated with insulin demand (r = 0.19; P = 0.19), or adiponectin (females: r = -0.37, P = 0.18; males: r = -0.16, P = 0.27), or resistin levels (r = +0.17; P = 0.21).Conclusion: Adiponectin levels and insulin demand were positively correlated during sepsis. Adiponectin levels were negatively correlated with epinephrine demand in male patients and epinephrine demand was positively correlated with resistin levels, which might have increased insulin resistance. The relationship between adiponectin and insulin action in humans is more complex than often suggested.Keywords: adipokines, sepsis, diabetes, resistin, leptin

BACKGROUND: In several neurodegenerative diseases, hyperphosphorylation at position Ser129 is found in fibrillar deposits of alpha-synuclein (asyn), implying a pathophysiological role of asyn phosphorylation in neurodegeneration. However, recent animal models applying asyn phosphorylation mimics demonstrated a protective effect of phosphorylation. Since metal-ion induced asyn oligomers were identified as a potential neurotoxic aggregate species with membrane pore-forming abilities, the current study was undertaken to determine effects of asyn phosphorylation on oligomer membrane binding. METHODS: We investigated the influence of S129 phosphorylation on interactions of metal-ion induced asyn oligomers with small unilamellar lipid vesicles (SUV) composed of POPC and DPPC applying the phosphorylation mimic asyn129E. Confocal single-particle fluorescence techniques were used to monitor membrane binding at the single-particle level. RESULTS: Binding of asyn129E monomers to gel-state membranes (DPPC-SUV) is slightly reduced compared to wild-type asyn, while no interactions with membranes in the liquid-crystalline state (POPC-SUV) are seen for both asyn and asyn129E. Conversely, metal-ion induced oligomer formation is markedly increased in asyn129E. Surprisingly, membrane binding to POPC-SUV is nearly absent in Fe(3+) induced asyn129E oligomers and markedly reduced in Al(3+) induced oligomers. CONCLUSION: The protective effect of pseudophosphorylation seen in animal models may be due to impeded oligomer membrane binding. Phosphorylation at Ser129 may thus have a protective effect against neurotoxic asyn oligomers by preventing oligomer membrane binding and disruption of the cellular electrophysiological equilibrium. Importantly, these findings put a new complexion on experimental pharmaceutical interventions against POLO-2 kinase.

Lehrpersonen erweisen sich häufig als schwierige Klientel, was die Einbindung in Forschungsprojekte betrifft. Neben Problemstellungen wie geringen Rücklaufquoten bei Befragungen fiel in der das Projekt "LeguPan – Lehrergesundheit: Prävention an Schulen" begleitenden quantitativen Evaluation eine hohe Zahl von Fragebögen auf, die mit Kommentaren, Anmerkungen und ikonografischen Zeichen versehen waren. Die vorliegende Untersuchung folgt der These, dass diese ein kommunikatives Anliegen oder Angebot an die Durchführenden der Evaluation darstellen. Alle Fragenbögen wurden daher nach Kommentaren, Anmerkungen und ikonografischen Zeichen gescreent und diese wurden exzerpiert. Die Auswertung dieser als Kommunikationsangebote verstandenen Textstellen orientiert sich am Verfahren der qualitativen Inhaltsanalyse. Alle Kommentare und ikonografischen Zeichen wurden Kategorien zugeordnet. Dabei ergaben sich folgende Kategorien: Bestreiten der Passung eines Items oder eines Messinstruments, Einschränken der Aussagekraft einer Antwort, die Begründung oder Rechtfertigung einer Antwort sowie Verständnisfragen und (meist unspezifische) Befindlichkeitsäußerungen. Aus dem kommunikativen Anliegen bzw. den erarbeiteten Kategorien lassen sich in einem ersten Schritt Schlüsse über Lehrkräfte als die Zielgruppe von Forschung ableiten. In einem zweiten Schritt werden Folgerungen für die Planung und Durchführung von Evaluationen und Projekten ausgearbeitet. Diese beziehen sich vor allem auf die sprachliche Aufbereitung, die Instruktion und Strategien für den Umgang mit sensiblen Themen in Befragungen. Qualitative Forschung ist so handlungsleitend für quantitative Erhebungen. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs130389

BACKGROUND: Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. Differential diagnosis with cystic echinococcosis (CE) caused by E. granulosus and AE is challenging. We aimed at improving diagnosis of AE on paraffin sections of infected human tissue by immunohistochemical testing of a specific antibody. METHODOLOGY/PRINCIPAL FINDINGS: We have analysed 96 paraffin archived specimens, including 6 cutting needle biopsies and 3 fine needle aspirates, from patients with suspected AE or CE with the monoclonal antibody (mAb) Em2G11 specific for the Em2 antigen of E. multilocularis metacestodes. In human tissue, staining with mAb Em2G11 is highly specific for E. multilocularis metacestodes while no staining is detected in CE lesions. In addition, the antibody detects small particles of E. multilocularis (spems) of less than 1 µm outside the main lesion in necrotic tissue, liver sinusoids and lymphatic tissue most probably caused by shedding of parasitic material. The conventional histological diagnosis based on haematoxylin and eosin and PAS stainings were in accordance with the immunohistological diagnosis using mAb Em2G11 in 90 of 96 samples. In 6 samples conventional subtype diagnosis of echinococcosis had to be adjusted when revised by immunohistology with mAb Em2G11. CONCLUSIONS/SIGNIFICANCE: Immunohistochemistry with the mAb Em2G11 is a new, highly specific and sensitive diagnostic tool for AE. The staining of small particles of E. multilocularis (spems) outside the main lesion including immunocompetent tissue, such as lymph nodes, suggests a systemic effect on the host.

Background. Assessment of white adipose tissue has changed in recent years, with WAT now being considered as an active endocrine organ, secreting a large number of bioactive mediators, so-called adipokines. Besides other functions, these adipokines are involved in inflammatory response thereby exhibiting predominantly proinflammatory or anti-inflammatory properties and contribute to insulin resistance. Methods. Comprehensive review of the literature of the role of adipokines relevant to critical care medicine using PubMed search. Results. Adiponectin—the prototype of an anti-inflammatory and insulin-sensitizing adipokine—is diminished in sepsis, while resistin—a protein with proinflammatory properties—is elevated. Plasminogen activator inhibitor-1, interleukin (IL)-1, IL-6, IL-8, and IL-10, and tumor-necrosis-factor-alpha mediate insulin resistance and are elevated in sepsis, while retinol-binding protein-4 concentrations are significantly reduced in sepsis. Chemerin displays potent anti-inflammatory and insulin-resistance properties, while monocyte chemotactic protein-1—increased in sepsis—contributes to macrophage infiltration in adipose tissue and insulin resistance. Conclusions. The expression of adipokines in humans is altered as well in obese as in septic patients with elevated levels of proinflammatory adipokines. Changes in adipokine levels in acute sepsis could contribute to insulin resistance. Consequently, in critically ill patients, these alterations underline a possible contribution of adipokines in the development of hyperglycemia.