Aortic Steal Correlates with Acute Organ Dysfunction and Short-Term Outcomes in Neonates with Vein of Galen Malformation.

INTRODUCTION: Vein of Galen aneurysmal malformation (VGAM) is a rare, congenital cerebrovascular malformation with high morbidity and mortality. Parameters to foresee clinical progression and allow individualized parent counseling are lacking. The aim of this study was to evaluate aortic steal measured by Doppler ultrasound as a prognostic parameter in these neonates. METHODS: A retrospective monocentric analysis of cardiac ultrasound exams before embolization in neonates with VGAM was conducted. Percentage of aortic steal measured by time-averaged maximum velocity above and below the zero flow baseline by pulsed Doppler ultrasound at the preductal aortic isthmus was calculated. Association of aortic steal with parameters of acute organ dysfunction (Bicêtre neonatal evaluation score [BNES], neonatal multiple organ dysfunction score [NeoMODS]) and mortality and determination of correlation between aortic steal and cerebral damage on initial and follow-up cerebral magnetic resonance imaging (cMRI) were evaluated. RESULTS: Twelve neonates were included, of which 3 died. Per 10 percentage point increase of aortic steal, BNES decreased by 1.64 (95% confidence interval [CI]: 1.28-2.0) points and the maximum observed NeoMODS increased by 1.25 (CI: 0.94-1.57) points. The odds for mortality increased by 2.3 (CI: 1.14-13.67) per 10 percentage point increase of aortic steal. There was a correlation between aortic steal and cerebral damage at baseline (white matter ρ [rho] = 0.34, gray matter ρ = 0.81) and follow-up (white matter ρ = 0.80, gray matter ρ = 0.72). CONCLUSION: The degree of aortic steal in neonates with VGAM was highly associated with the severity of organ dysfunction, disease progression on cMRI, and mortality.

Review on Pediatric Malignant Focal Liver Lesions with Imaging Evaluation: Part I.

Malignant focal liver lesions (FLLs) are commonly reported in adults but rarely seen in the pediatric population. Due to the rarity, the understanding of these diseases is still very limited. In children, most malignant FLLs are congenital. It is very important to choose appropriate imaging examination concerning various factors. This paper will outline common pediatric malignant FLLs, including hepatoblastoma, hepatocellular carcinoma, and cholangiocarcinoma and discuss them against the background of the latest knowledge on comparable/similar tumors in adults. Medical imaging features are of vital importance for the non-invasive diagnosis and follow-up of treatment of FLLs in pediatric patients. The use of CEUS in pediatric patients for characterizing those FLLs that remain indeterminate on conventional B mode ultrasounds may be an effective option in the future and has great potential to be integrated into imaging algorithms without the risk of exposure to ionizing radiation.

Review on Pediatric Malignant Focal Liver Lesions with Imaging Evaluation: Part II.

Malignant focal liver lesions (FLLs) represent various kinds of epithelial and mesenchymal tumors. In pediatric patients, the understanding of pediatric liver diseases and associated imaging manifestations is essential for making accurate diagnosis and differential diagnosis. This paper will discuss the latest knowledge of the common pediatric malignant FLLs, including undifferentiated embryonal sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant rhabdoid tumor. Medical imaging features are not only helpful for clinical diagnosis, but can also be useful in the evaluation and follow-up of pre- and post-treatment. The future perspectives of contrast-enhanced ultrasound (CEUS) enhancement patterns of FLLs in pediatric patients are also mentioned.

Pulmonary Sonography - Neonatal Diagnosis Part 2. / Lungensonografie ­ Diagnostik in der Neonatologie Teil 2.

A healthy, air-filled lung can only be visualized by its artifacts, and pathologies of the lung are revealed by changes in these artifacts. Because ultrasound artifacts are predominantly used in pulmonary sonography to assess pathologic processes, the variability of sonographically imageable phenomena is limited. For this reason, different pulmonary diseases may present very similarly in ultrasound. Therefore, a correct interpretation of the findings is only possible in the clinical context, taking into account the age-dependent differential diagnoses.The particular relevance of lung ultrasound in the treatment of neonatal patients results from a close correlation between the extent of sonographically-depictable pathologies and parameters of respiratory insufficiency. This suggests a direct correlation between ultrasound findings and the severity of lung injury. Lung ultrasound thus represents a unique, ubiquitously available, bedside, serial method for monitoring the pulmonary status.

Pulmonary Sonography - Neonatal Diagnosis Part 1. / Lungensonografie ­ Diagnostik in der Neonatologie Teil 1.

Diseases of the respiratory system are among the main problems of premature patients in the neonatal intensive care unit. Radiography of the thorax is the gold standard of imaging. This results in high cumulative radiation exposure with potential negative long-term consequences. Ultrasound examination of thoracic structures represents a promising radiation-free and ubiquitously available alternative.A healthy, ventilated lung can only be imaged via artifacts, since total reflection of the sound waves occurs due to the high impedance difference between tissue and air-filled lung. Pathologies of pleura and subpleural lung tissue lead to changes in the acoustic properties of the tissue and thus to variations in the artifacts that can be imaged. The main sonographic characteristics of pulmonary pathology are: pleural line abnormalities, increased B-lines and comet-tail artifacts, lung consolidations, a visible pulmonary pulse, pleural sliding abnormalities, and visualization of effusions. Deviations from normal sonographic findings can be assigned to specific underlying pathophysiologies, so that conclusions about the disease can be drawn in conjunction with the clinical symptoms.

Prevalence of xerostomia and hyposalivation and their association with quality of life in elderly patients in dependence on dental status and prosthetic rehabilitation: a pilot study.

OBJECTIVES: The aims of this pilot study were to investigate the prevalence of xerostomia and hyposalivation and their impact on quality of life in a cohort of elderly patients including dental status and the character of potential prosthetic restorations as independent variables. METHODS: Patients aged 60 years or older without any objective or subjective need for prosthodontic treatment taking part in a regular recall programme were included in the trial. Quality of life was assessed using the German version of the GOHAI; prevalence and severity of xerostomia was investigated using the shortened version of the Xerostomia Inventory (XI). Stimulated salivary flow rate was determined using a sialometric approach. Dental status and the character of prosthetic restorations (no/fixed restorations and removable but tooth-supported dentures vs. gum-supported dentures) were assessed in a clinical examination by experienced dentists specialized in prosthodontic treatment. RESULTS: A total of 68 patients were included in the trial; a prevalence of xerostomia of 16% and a prevalence of hyposalivation of 31% were identified. The quality of life in the study cohort decreased significantly as a function of xerostomia severity but not salivary flow; moreover, a significant impact of the number of teeth/implants in the upper jaw and the presence of gum-supported dentures in both jaws on GOHAI scores could be identified. CONCLUSIONS: Within the limitations of a pilot study, the results support the assumption that the quality of life in elderly patients is particularly related to their subjective perception of xerostomia. A decline in salivary flow, the dental status and the character of prosthetic restorations appear to play a subordinate role for the quality of life in elderly patients. CLINICAL SIGNIFICANCE: The quality of life in elderly patients may be severely diminished due to an increased subjective perception of dry mouth. Dental treatment should focus on alleviating xerostomia, whereas the impact of dental status and prosthetic restoration appear to be subordinate.

Combination effects of digalloylresveratrol with arabinofuranosylcytosine and difluorodeoxycytidine in human leukemia and pancreatic cancer cells.

Digalloylresveratrol (DIG) is a newly synthesized agent aimed to combine the biological effects of the natural compounds, gallic acid and resveratrol, which both are free radical scavengers exhibiting anticancer activity. In this study, we investigated the effects of DIG on the growth of human HL-60 leukemia cells and on the colony formation of human BxPC-3 and PANC-1 pancreatic cancer cells. DIG was applied alone and in combination with arabinofuranosylcytosine (Ara-C) or difluorodeoxycytidine (dFdC), depending on the cell line employed. All IC(50) values observed were in the low micromolar range rendering DIG a promising antitumor compound in vitro. Considering the combination experiments, DIG yielded additive effects with Ara-C in HL-60 cells and-to a lesser extent-with dFdC in BxPC-3 and PANC-1 cells. Owing to our results, DIG may be further investigated in vitro and in animals.

Perceived stress and team performance during a simulated resuscitation.

PURPOSE: Barriers to optimal performance of cardiopulmonary resuscitation may partly relate to human factors, such as stress and specific emotions. The aim of this study was to investigate whether mental stress and different perceived emotions have a negative impact on the performance of rescuers. METHODS: This prospective, observational study was conducted at the Simulator Center of the University Hospital Basel, Switzerland. A total of 120 medical students (70% female) participated in teams of three. They reported levels of perceived stress, feeling overwhelmed, motivation and specific emotions before, during, and after a simulated resuscitation. The association of stress/overload (index of stress and feeling overwhelmed), motivation, and specific emotions with resuscitation performance defined as hands-on time during the first 180 s after cardiac arrest was investigated. RESULTS: During resuscitation, levels of stress/overload, motivation, and negative emotions were significantly higher as compared to the periods before and after resuscitation. In contrast, positive emotions were highest before and after resuscitation and significantly lower during resuscitation. In general, females reported higher stress/overload and negative emotions, whereas males reported more positive emotions. A multivariate linear regression model showed negative associations of stress/overload (regression coefficient -18.12, 95% CI -30.73, -5.51, p = 0.006) and positive associations of motivation (regression coefficient 13.45, 95% CI 0.95, 25.95, p = 0.036) with resuscitation performance. CONCLUSION: A simulated cardiac arrest caused substantial perceived stress/overload and negative emotions, particularly in female students, which adversely impacted resuscitation performance. Further studies are required to expand our findings to more experienced medical professionals and investigate whether stress coping strategies improve resuscitation performance.

3D QSAR analyses-guided rational design of novel ligands for the (alpha4)2(beta2)3 nicotinic acetylcholine receptor.

Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)2(beta2)3 nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r2 = 0.928, q2 = 0.692, no. of components = 3; CoMSIA r2 = 0.899, q2 = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r2 values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)2(beta2)3 subtype, demonstrate the high quality of the 3D QSAR models.

Synthesis and nicotinic binding studies on enantiopure diazine analogues of the novel (2-chloro-5-pyridyl)-9-azabicyclo[4.2.1]non-2-ene UB-165.

As part of our program aimed at optimizing therapeutic effects over toxic effects (as observed in the naturally occurring nicotinic acetylcholine receptor modulators (-)-nicotine, (-)-epibatidine, (-)-ferruginine, and (+)-anatoxin-a), we investigated the bioisosteric potential of diazines in the field of (+)-anatoxin-a-type structures. In the series of diazine analogues of deschloro-UB-165 (DUB-165, 6), bioisosteric replacement of the 3-pyridyl pharmacophoric element by a 4-pyridazinyl, 5-pyrimidinyl, or 2-pyrazinyl moiety resulted in novel nAChR ligands 7, 8, and 9. A palladium-catalyzed Suzuki cross-coupling of the 3-diethylboranylpyridine (14) and a Stille cross-coupling of the corresponding tributylstannyl diazines 15-17 with the vinyl triflate 13 of the N-protected 9-azabicyclo[4.2.1]nonan-2-one 12 constitute the key steps in the syntheses of these enantiopure anatoxinoids 6-9. Studies of the in vitro affinity for (alpha4)(2)(beta2)(3), alpha3(beta)4, and alpha7 nAChR subtypes by radioligand binding assays demonstrated that the diazine analogues 7-9 can be considered as pharmacologically attractive bioisosteres of DUB-165 (6) but with different effects on the binding affinity with regard to the diazine moiety. The pyrimidine-containing bioisostere 8 turned out to be the most active diazine analogue, which interacts potently (K(i) = 0.14 nM) with the (alpha4)(2)(beta2)(3) subtype and differentiates significantly among the nAChR subtypes investigated. The nitrogens in this anatoxinoid 8 show by far the most negative atomic charges (calculated using the AM1 Hamiltonian). This qualitatively correlates with the highest binding affinity observed for 8 for all subtypes under consideration.

Syntheses and evaluation of pyridazine and pyrimidine containing bioisosteres of (+/-)-pyrido[3.4-b]homotropane and pyrido-[3.4-b]tropane as novel nAChR ligands.

Bioisosteric replacement of the pyridine pharmacophoric element in (+/-)-pyrido[3.4-b]homotropane (PHT) and pyrido[3.4-b]tropane with the pyridazine and pyrimidine nucleus resulted in hitherto unknown nAChR ligands such as 5-8. Inverse type Diels-Alder reactions constitute the key steps in the new routes to the pyridazine- or pyrimidine-annulated bioisosteres. The enantiopure (+)-2-tropinone (11) from the 'chiral pool' is transformed to the ring-expanded silyl enol ether 12 and to the enamine 15. Both proved to be highly dienophilic species in the inverse type [4+2] cycloaddition reactions with the 1,2,4,5-tetrazines 13 and 16a,b or with the 1,3,5-triazine 19 to provide the enantiopure target compounds 5-7. In the same way the racemic pyrimidine-annulated species 8 was obtained from 3-tropanone 21. The new ligands were tested for their in vitro affinity for (alpha4)2(beta2)3 and alpha7* nAChR subtype. In comparison to PHT, well known to exhibit affinity for agonist binding sites in rat brain approximately equivalent to that of (+)-anatoxin-a (1), replacement of the pyridine by the bioisosteric pyridazine resulted in 30-fold lower affinity at the (alpha4)2(beta2)3 subtype. The annulated diazinotropanes 6-8, ligands with ferruginine-like structures more or less retained the affinity of (-)-norferruginine (3) except of compound 7. Remarkably, all of the novel ligands are devoid of affinity at the alpha7* subtype.