Prefrontal gray matter volume mediates genetic risks for obesity.

Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

Sonographic discrimination between benign and malignant adnexal masses in premenopause.

PURPOSE: The aim of this study was to assess the diagnostic value of sonographic pattern recognition by experts, a standardized morphological scoring system, the risk malignancy index (RMI) and CA 125 assay for the preoperative assessment of ovarian lesions in premenopausal patients. MATERIAL AND METHODS: Diagnostic work-up of 1320 patients who underwent surgical exploration due to an adnexal mass at a tertiary referral center were included. We assessed the discriminative value of pattern recognition, a sonographic morphological scoring system, RMI and CA 125 by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa for each diagnostic approach while using histopathology as the reference standard. RESULTS: Pattern recognition showed the highest discriminative power with an observed kappa of 0.53. Sensitivity and specificity yielded 0.76 and 0.97 respectively. Combining pattern recognition with CA 125 serum measurement in the context of a triage system diminished the diagnostic value (kappa: 0.24; sensitivity: 0.29 specificity: 0.97). For the RMI we observed a sensitivity of 0.54 and a specificity of 0.96 and estimated kappa value yielded 0.37. Omitting the CA 125 assay and using a morphological sonographic assessment system increased the kappa value to 0.45 with sensitivity and specificity observed at 0.61 and 0.97 respectively. CONCLUSION: Expert pattern recognition was found to be the method with the highest discriminative power in assessing an adnexal mass during premenopause. Additional assessment of serum CA 125 diminished the diagnostic accuracy. Standardized morphological sonographic assessment resulted in a moderate diagnostic accuracy. Supplementing the morphological sonographic assessment with CA 125 by using the RMI algorithm did not improve the diagnostic value.

Monocyte haptotaxis induced by the RANTES chemokine.

BACKGROUND: Soluble mediators and inducible cell-surface molecules coordinate the ordered cascade of events giving rise to inflammation. The specific mechanisms underlying the attraction of antigen-specific cells into a site of inflammation remain sketchy, however. In particular, it is unclear how chemoattractants cause rapidly moving immune cells to adhere to the blood vessel wall and to enter inflamed tissues. RESULTS: Here we show that RANTES, a potent chemo-attractant for monocytes and T lymphocytes, is inducibly expressed within an inflamed organ, binds to endothelial cells, and promotes haptotaxis, the migration of cells induced by surface-bound gradients. CONCLUSION: These findings lead us to propose a model for the role of RANTES in the migration of antigen-specific immune cells into an inflammatory site.

[Decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension]. / Dekompensierte Rechtsherzinsuffizienz, Intensiv- und Perioperativ-Management bei Patienten mit pulmonaler Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.

Indomethacin reduces substance P levels in human ocular aqueous humor.

Substance P immunoreactivity was measured by radioimmunoassay in aqueous humor samples of patients treated 13 h earlier with gentamicin, indomethacin or timolol. The indomethacin-treated group showed significantly decreased levels of substance P. The indomethacin effect is due to inhibition of the synthesis of arachidonic acid metabolites or involves non-specific mechanisms. It is suggested that suppression of substance P release may contribute to therapeutic effects of indomethacin in the human eye in conditions such as surgical miosis.

Orthotopic liver transplantation in a patient with severe portopulmonary hypertension.

Liver transplantation in patients with severe portopulmonary hypertension (PPH) has been associated with mortality rates in the range of 70% to 80%. Preoperative long-term epoprostenol therapy reverses pulmonary hypertension and may be a valuable possibility to reduce mortality in patients with severe PPH undergoing orthotopic liver transplantation. We want to report a patient with severe PPH, who was treated with intravenous epoprostenol for an 8-month period, after which pulmonary vascular resistance had decreased from 12 to 3 Wood units. Nevertheless, the patient developed intractable perioperative right heart failure necessitating transient mechanical circulatory support. The patient was weaned from mechanical circulatory support, but died from another episode of acute right heart failure after 28 days. Complicated liver transplantation associated with major cardiovascular stress is obviously not tolerated in patients with severe portopulmonary hypertension even after preoperative long-term epoprostenol therapy.

Multicentre study of fetal cardiac time intervals using magnetocardiography.

OBJECTIVE: A database with reference values of the durations of the various waveforms in a magnetocardiogram of fetuses in uncomplicated pregnancies is assessed. This database will be of help to discriminate between pathologic and healthy fetuses. A fetal magnetocardiogram is a recording of the magnetic field in a location near the maternal abdomen and reflects the electric activity within the fetal heart. It is a non-invasive method, which can be used with nearly 100% reliability from the 20th week of gestation onward. DESIGN: Durations of the waveforms were assembled from averaged magnetocardiograms and statistically processed. SETTING: Fetal magnetocardiograms were measured with different magnetocardiographs. All measurements were carried out in magnetically shielded rooms. SAMPLE: Fetal magnetocardiograms were obtained for 582 healthy patients. METHOD: The durations of the waveforms were extracted from fetal magnetocardiograms measured at the cooperating centres. The variables collected included the duration of the P-wave, the PR interval, the PQ interval, the QRS complex, the QT interval and the T-wave and QTc value. The results were compared with values extracted from electrocardiograms of fetuses measured via electrodes attached to the maternal abdomen, from electrocardiograms measured during labour using a scalp electrode, and from electrocardiograms recorded in newborns, that were found in the literature. MAIN OUTCOME MEASURES: Values of the durations are given as a function of gestational age including the regression line as well as the bounds marking the 90%, 95% and 98% prediction interval. RESULTS: The durations of the P-wave, the PR interval, the QRS complex, the QT interval and QTc value increase linearly with gestational age. The durations of the PQ interval and the T-wave are independent of fetal age. CONCLUSION: The values found agree with those found in the literature. The scatter of the data is wide due to the variation in normal physiology, the measuring system and signal processing and the subjectivity of the researcher. However, the system can define normal ranges and may be used in diagnosis.