Staphylococcus aureus Serine protease-like protein A (SplA) induces IL-8 by keratinocytes and synergizes with IL-17A.

BACKGROUND: Serine protease-like (Spl) proteins produced by Staphylococcus (S.) aureus have been associated with allergic inflammation. However, effects of Spls on the epidermal immune response have not been investigated. OBJECTIVES: To assess the epidermal immune response to SplA, SplD and SplE dependent on differentiation of keratinocytes and a Th2 or Th17 cytokine milieu. METHODS: Human keratinocytes of healthy controls and a STAT3-hyper-IgE syndrome (STAT3-HIES) patient were cultured in different calcium concentrations in the presence of Spls and Th2 or Th17 cytokines. Keratinocyte-specific IL-8 production and concomitant migration of neutrophils were assessed. RESULTS: SplE and more significantly SplA, induced IL-8 in keratinocytes. Suprabasal-like keratinocytes showed a higher Spl-mediated IL-8 production and neutrophil migration compared to basal-like keratinocytes. Th17 cytokines amplified Spl-mediated IL-8 production, which correlated with neutrophil recruitment. Neutrophil recruitment by keratinocytes of the STAT3-HIES patient was similar to healthy control cells. CONCLUSION: S. aureus-specific Spl proteases synergized with IL-17A on human keratinocytes with respect to IL-8 release and neutrophil migration, highlighting the importance of keratinocytes and Th17 immunity in barrier function.

Impacts of metal mining on river systems: a global assessment.

An estimated 23 million people live on floodplains affected by potentially dangerous concentrations of toxic waste derived from past and present metal mining activity. We analyzed the global dimensions of this hazard, particularly in regard to lead, zinc, copper, and arsenic, using a georeferenced global database detailing all known metal mining sites and intact and failed tailings storage facilities. We then used process-based and empirically tested modeling to produce a global assessment of metal mining contamination in river systems and the numbers of human populations and livestock exposed. Worldwide, metal mines affect 479,200 kilometers of river channels and 164,000 square kilometers of floodplains. The number of people exposed to contamination sourced from long-term discharge of mining waste into rivers is almost 50 times greater than the number directly affected by tailings dam failures.

Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus.

INTRODUCTION: The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. PATIENTS AND METHODS: We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. RESULTS: Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. DISCUSSION: Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.

Outcomes for Pressure Ulcer Trials (OUTPUTs) project: review and classification of outcomes reported in pressure ulcer prevention research.

In order to overcome inconsistencies in the reporting of outcomes in clinical trials, core outcome sets (COSs) have been developed in many clinical areas and the awareness of this concept is growing steadily. The Outcomes for Pressure Ulcer Trials (OUTPUTs) project aims to improve the quality of evidence from pressure ulcer prevention trials by developing a COS. As an initial step in the COS process we aimed to identify and classify both outcomes and concepts that represent potential outcomes for future trials that have been reported in pressure ulcer prevention research. A review was conducted in 12 major databases covering the literature indexed until 2016. Outcomes and relevant concepts reported in primary studies and/or reviews on pressure ulcer prevention in adult patients were extracted as presented in the articles, and afterwards inductively grouped into outcome domains. The domains were then categorized according to the outcome domain taxonomy recently proposed by the COMET group. In total 332 studies were included and 68 outcome domains were identified, covering multiple aspects of pressure ulcer prevention. Pressure ulcer occurrence was reported in 71% of all included studies, representing the most frequent outcome, followed by costs (22% of all studies) and acceptability of intervention and comfort (18% of all studies). A plethora of different outcomes are applied in pressure ulcer prevention research and substantial variations in definitions and reporting of similar outcomes were observed. A COS for pressure ulcer prevention trials is needed to overcome the noncomparability of outcomes.

The effectiveness of two silicone dressings for sacral and heel pressure ulcer prevention compared with no dressings in high-risk intensive care unit patients: a randomized controlled parallel-group trial.

BACKGROUND: There is a high incidence of pressure ulcers in high-risk settings such as intensive care. There is emerging evidence that the application of dressings to pressure ulcer predilection areas (sacrum and heels) improves prevention strategies. OBJECTIVES: To determine whether preventive dressings, applied to the sacrum and heels of high-risk patients in intensive care units, in addition to standard prevention, reduces the incidence of pressure ulcers. METHODS: Between June 2015 and July 2018, a randomized, controlled, two-arm, superiority pragmatic study was performed with a concealed 1 : 1 allocation to the intervention and control group. Patients assigned to the intervention group had dressings applied to the sacrum and heels. RESULTS: In total, 7575 patients were screened for eligibility and 475 patients were included and allocated to both groups. Finally, 212 patients in the intervention group and 210 in the control group were analysed. The mean age was 63·5 years and the majority of patients were male (65·4%). The cumulative pressure ulcer incidence category II and above was 2·8% in the intervention, and 10·5% in the control group (P = 0·001). Compared with the control group, the relative risk in the intervention group was 0·26 [95% confidence interval (CI) 0·11-0·62] and the absolute risk reduction was 0·08 (95% CI 0·03-0·13). CONCLUSIONS: The results indicate that the application of dressings, in addition to standard prevention, in high-risk intensive care unit patients is effective in preventing pressure ulcers at the heels and sacrum. What's already known about this topic? Pressure ulcers are severe soft tissue injuries and wounds, which occur worldwide in all healthcare settings. Despite preventive interventions, pressure ulcers still develop. There is emerging evidence that dressings help to prevent pressure ulcers. What does this study add? The incidence of pressure ulcers in intensive care units among high-risk patients remains high. The application of dressings to the sacrum and heels, in addition to standard preventive measures, reduces the relative and absolute risks for the development of pressure ulcers. The application of preventive dressings at the heels and sacrum seems to be feasible in intensive care settings.

Depressive symptoms, impaired glucose metabolism, high visceral fat, and high systolic blood pressure in a subgroup of women with recent gestational diabetes.

Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 ± 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.

Serum and plasma amino acids as markers of prediabetes, insulin resistance, and incident diabetes.

Presently, routine screening misses many cases of prediabetes and early type 2 diabetes (T2D). Therefore, better biomarkers are needed for a simple and early detection of abnormalities of glucose metabolism and prediction of future T2D. Possible candidates for this include plasma or serum amino acids because glucose and amino acid metabolism are closely connected. This review presents the available evidence of this connectivity and discusses its clinical implications. First, we examine the underlying physiological, pre-analytical, and analytical issues. Then, we summarize results of human studies that evaluate amino acid levels as markers for insulin resistance, prediabetes, and future incident T2D. Finally, we illustrate the interconnection of amino acid levels and metabolic syndrome with our own data from a deeply phenotyped human cohort. We also discuss how amino acids may contribute to the pathophysiology of T2D. We conclude that elevated branched-chain amino acids and reduced glycine are currently the most robust and consistent amino acid markers for prediabetes, insulin resistance, and future T2D. Yet, we are cautious regarding the clinical potential even of these parameters because their discriminatory power is insufficient and their levels depend not only on glycemia, but also on other components of the metabolic syndrome. The identification of more precise intermediates of amino acid metabolism or combinations with other biomarkers will, therefore, be necessary to obtain in order to develop laboratory tests that can improve T2D screening.

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVES: Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR. METHODS: 88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS). RESULTS: The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS. CONCLUSION: Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

Insulin secretory defect in familial partial lipodystrophy Type 2 and successful long-term treatment with a glucagon-like peptide 1 receptor agonist.

BACKGROUND: Familial partial lipodystrophies are rare monogenic disorders that are often associated with diabetes. In such cases, it can be difficult to achieve glycaemic control. CASE REPORT: We report a 34-year old woman with familial partial lipodystrophy type 2 (Dunnigan) and diabetes; her hyperglycaemia persisted despite metformin treatment. A combined intravenous glucose tolerance-euglycaemic clamp test showed severe insulin resistance, as expected, but also showed strongly diminished first-phase insulin secretion. After the latter finding, we added the glucagon-like peptide-1 receptor agonist liraglutide to the patient's treatment regimen, which rapidly normalized plasma glucose levels. HbA1c values <42 mmol/mol (6.0%) have now been maintained for over 4 years. CONCLUSION: This case suggests that a glucagon-like peptide-1 receptor agonist may be a useful component of glucose-lowering therapy in individuals with familial partial lipodystrophy and diabetes mellitus.

Physical fitness and plasma leptin in women with recent gestational diabetes.

AIMS/HYPOTHESIS: Low physical fitness (PF) is a risk factor for type 2 diabetes mellitus (T2D). Women with a history of gestational diabetes (GDM) are at risk for T2D at a young age, but the role of PF in this population is not clear. PF has also been found to correlate inversely with plasma leptin in previous studies. Here, we examine whether women who had GDM have lower PF than women after a normoglycemic pregnancy and, second, whether PF is associated with plasma leptin, independently of body fat mass. METHODS: Cross-sectional analysis of 236 participants in the PPSDiab Study (cohort study of women 3-16 months after delivery, 152 after gestational diabetes (pGDM), 84 after normoglycemic pregnancy (control subjects); consecutively recruited 2011-16); medical history, physical examination with bioelectrical impedance analysis (BIA), whole body magnetic resonance imaging (MRI) (n = 154), 5-point oral glucose tolerance test, cardiopulmonary exercise testing, clinical chemistry including fasting plasma leptin; statistical analysis with Mann-Whitney U and t -test, Spearman correlation coefficient, multiple linear regression. RESULTS: Women pGDM had lower maximally achieved oxygen uptake (VO2peak/kg: 25.7(21.3-29.9) vs. 30.0(26.6-34.1)ml/min/kg; total VO2peak: 1733(1552-2005) vs. 1970(1767-2238)ml/min; p<0.0001 for both), and maximum workload (122.5(105.5-136.5) vs. 141.0(128.5-159.5)W; p<0.0001). Fasting plasma leptin correlated inversely with PF (VO2peak/kg ρ = -0.72 p<0.0001; VO2peak ρ = -0.16 p = 0.015; max. load ρ = -0.35 p<0.0001). These associations remained significant with adjustment for body mass index, or for body fat mass (BIA and MRI). CONCLUSIONS/INTERPRETATION: Women with a recent history of GDM were less fit than control subjects. Low PF may therefore contribute to the risk for T2D after GDM. This should be tested in intervention studies. Low PF also associated with increased leptin levels-independently of body fat. PF may therefore influence leptin levels and signaling. This hypothesis requires further investigation.

Private land manager capacity to conserve threatened communities under climate change.

Major global changes in vegetation community distributions and ecosystem processes are expected as a result of climate change. In agricultural regions with a predominance of private land, biodiversity outcomes will depend on the adaptive capacity of individual land managers, as well as their willingness to engage with conservation programs and actions. Understanding adaptive capacity of landholders is critical for assessing future prospects for biodiversity conservation in privately owned agricultural landscapes globally, given projected climate change. This paper is the first to develop and apply a set of statistical methods (correlation and bionomial regression analyses) for combining social data on land manager adaptive capacity and factors associated with conservation program participation with biophysical data describing the current and projected-future distribution of climate suitable for vegetation communities. We apply these methods to the Tasmanian Midlands region of Tasmania, Australia and discuss the implications of the modelled results on conservation program strategy design in other contexts. We find that the integrated results can be used by environmental management organisations to design community engagement programs, and to tailor their messages to land managers with different capacity types and information behaviours. We encourage environmental agencies to target high capacity land managers by diffusing climate change and grassland management information through well respected conservation NGOs and farm system groups, and engage low capacity land managers via formalized mentoring programs.

Poor sleep quality is associated with impaired glucose tolerance in women after gestational diabetes.

We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02-1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM.

[Current concepts in diagnostics and therapy of diabetes mellitus]. / Aktuelle Konzepte in der Diagnostik und Therapie des Diabetes mellitus.

In Germany approximately 7.2% of the population currently suffer from diabetes mellitus. A further increase in the prevalence is expected in the coming years. Many therapy options, sometimes even without a risk of hypoglycemia, are now available. The foundations of a sufficient therapy of type 2 diabetes are, however, still lifestyle measures, such as weight reduction, optimized nutrition and increased physical activity. Optimization of cardiac and cerebrovascular risk factors is also an essential component of management of diabetes in order to reduce or even avoid secondary complications.

[Optimising pain therapy for neurological inpatients]. / Optimierung der Schmerztherapie an neurologischen Stationen.

BACKGROUND: The Department of Neurology at the Medical University Graz has implemented a multiprofessional pain management concept and evaluated the outcome by means of a patient survey. METHODS: Standard operating procedures for standardised pain measurement, documentation and therapy were developed. All engaged professional participants were trained before implementation. RESULTS: 88.7 % of the surveyed 63 patients reported pain during the hospitalisation. During the night and in the morning, the occurrence of severe pain was most likely. The position or activity most likely triggering severe pain was mobilisation (19 %). Patients with degenerative diseases of the spine without radiculopathy reported the highest levels of pain. CONCLUSIONS: Pain is an important problem for neurological inpatients. Nocturnal pain, pain induced by mobilisation, and pain therapy for patients with degenerative diseases of the spine without radiculopathy require particular attention.

Characterizing spatial uncertainty when integrating social data in conservation planning.

Recent conservation planning studies have presented approaches for integrating spatially referenced social (SRS) data with a view to improving the feasibility of conservation action. We reviewed the growing conservation literature on SRS data, focusing on elicited or stated preferences derived through social survey methods such as choice experiments and public participation geographic information systems. Elicited SRS data includes the spatial distribution of willingness to sell, willingness to pay, willingness to act, and assessments of social and cultural values. We developed a typology for assessing elicited SRS data uncertainty which describes how social survey uncertainty propagates when projected spatially and the importance of accounting for spatial uncertainty such as scale effects and data quality. These uncertainties will propagate when elicited SRS data is integrated with biophysical data for conservation planning and may have important consequences for assessing the feasibility of conservation actions. To explore this issue further, we conducted a systematic review of the elicited SRS data literature. We found that social survey uncertainty was commonly tested for, but that these uncertainties were ignored when projected spatially. Based on these results we developed a framework which will help researchers and practitioners estimate social survey uncertainty and use these quantitative estimates to systematically address uncertainty within an analysis. This is important when using SRS data in conservation applications because decisions need to be made irrespective of data quality and well characterized uncertainty can be incorporated into decision theoretic approaches.

Plasma MR-proANP levels are associated with carotid intima-media thickness in the general community: the KORA F4 study.

OBJECTIVE: Subjects with metabolic syndrome (MetS) and individuals with type 2 diabetes are at high risk for vascular complications. Hormones acting on vascular endothelium may be involved in the atherogenic process associated with metabolic disorders. The objective of this study was to determine the correlation of pro-atrial natriuretic hormone (proANP) with the presence of subclinical atherosclerosis. METHODS: In 1272 subjects participating in the KORA F4 study, we determined plasma levels of mid-regional proANP (MR-proANP) and the intima-media thickness (IMT) of the carotid artery. We used logistic regression models to investigate the relation of MR-proANP with components of MetS and IMT. RESULTS: In multiple adjusted regression models, MR-proANP levels were inversely associated with MetS (OR = 0.66, 95% CI 0.47-0.93), central obesity (OR = 0.67, 95% CI 0.46-0.96), raised triglyceride levels (OR = 0.53, 95% CI 0.37-0.77), prediabetes (OR = 0.62, 95%, CI 0.44-0.87) and type 2 diabetes (OR = 0.55, 95% CI 0.35-0.88) when comparing the top quartile vs. the lower three quartiles. Furthermore, there was an inverse relationship between MR-proANP and IMT. After adjustment for traditional cardiovascular risk markers, individuals with high MR-proANP plasma levels in the top quartile (Q4) had significantly lower IMT values (Q4 vs. Q1-Q3: ß -0.0178, 95% CI -0.0344; -0.0013). CONCLUSIONS: In this population-based study, high plasma concentrations of MR-proANP were significantly associated with a lower incidence of MetS components and lower measures of early atherosclerosis. The data suggest a link between MR-proANP levels and the development of vascular complications.

[Update on type 1 diabetes]. / Update Typ-1-Diabetes.

Type 1a diabetes develops from a chronic autoimmune process leading to absolute insulin deficiency and proneness to ketosis. Prospective studies have clearly shown that intensive insulin therapy (ICT) results in improved quality of life and reduced development of diabetes-associated microvascular and macrovascular complications. The gold standard of therapy in type 1 diabetes is insulin injection with a basal bolus insulin regimen, in which patient daily routine and wishes are considered. The treatment goals should be determined on an individualized basis together with the patient. An HbA(1c) value < 7.0% is considered to be well controlled while values ≤ 6.5% indicate an excellent blood glucose control, as long as there are no episodes of severe hypoglycemia. As many adult patients with type 1 diabetes develop additional cardiovascular risk factors dyslipidemia and hypertension should also be considered and treated according to current treatment guidelines. A multimodal treatment may be the best way to preserve quality of life in patients with type 1 diabetes.

Suppression of the nuclear factor Eny2 increases insulin secretion in poorly functioning INS-1E insulinoma cells.

Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y)2, is a nuclear factor that participates in several steps of gene transcription and in mRNA export. We had previously found that Eny2 expression changes in mouse pancreatic islets during the metabolic adaptation to pregnancy. We therefore hypothesized that the protein contributes to the regulation of islet endocrine cell function and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2 had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased glucose and exendin-4-induced insulin secretion from otherwise poorly glucose-responsive INS-1E cells. Insulin content, cellular viability, and the expression levels of several key components of glucose sensing remained unchanged; however glucose-dependent cellular metabolism was higher after Eny2 knockdown. Suppression of Eny2 enhanced the intracellular incretin signal downstream of cAMP. The use of specific cAMP analogues and pathway inhibitors primarily implicated the PKA and to a lesser extent the EPAC pathway. In summary, we identified a potential link between the nuclear protein Eny2 and insulin secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced insulin release from a poorly glucose-responsive INS-1E subline. Whether these findings extend to other experimental conditions or to in vivo physiology needs to be determined in further studies.

Reduced urinary glutamate levels are associated with the frequency of migraine attacks in females.

BACKGROUND AND PURPOSE: Recent evidences indicate that glutamatergic homeostasis disorders are implicated in the pathogenesis of migraine. In particular, plasma and cerebrospinal fluid glutamate levels seem to be altered in migraine patients. However, the impacts of glutamate on migraine and especially on aura symptoms, alterations in the frequency of migraine attacks as well as investigations on glutamate on migraine-related metabolic dysfunctions, like hyperinsulinaemia, and an atherogenic lipid profile remain elusive to date. The aim of the present study was to investigate the impact of glutamate on migraine and related metabolic dysfunctions. METHODS: We investigated the urinary glutamate levels of female migraineurs (n = 48) in the interictal phase and healthy controls (n = 48). Parameters of the insulin- and lipid metabolism, inflammatory parameters and anthropometric parameters were additionally determined. RESULTS: Urinary glutamate levels of female migraineurs were significantly decreased with respect to the control group. Logistic regression revealed an odds ratio of 4.04 for migraine. We found a significant correlation with the time-period of patients' last attack and a significant inverse correlation with the annual frequency of migraine attacks. Other parameters of the insulin- and lipid metabolism, anthropometric and inflammatory parameters showed no significant correlation with glutamate levels. CONCLUSION: We show here that female migraineurs exhibit decreased urinary glutamate levels which are associated with a 4.04-fold higher risk for migraine and correlated with patients' frequency of migraine attacks.

[Gestational diabetes]. / Gestationsdiabetes.

Gestational diabetes is one of the most common complications during pregnancy. Its incidence has increased in recent decades. This is partly due to improved screening strategies and more stringent diagnostic criteria. Using the updated diagnostic thresholds, it is expected that 5-10% at least of all pregnant women will be diagnosed with diabetes mellitus. The rationale for the novel blood glucose criteria are data from prospective studies reporting an increase of fetal and maternal complications even when the blood glucose is only slightly increased. For the first time, solid evidence now exists for the diagnosis and treatment of gestational diabetes.