Dynamic changes of circulating miRNAs induced by the Ebola virus vaccine VSV-EBOV.

VSV-EBOV is a replication-competent Ebola virus (EBOV) vaccine, which was tested in clinical trials as response to the Ebola virus disease (EVD) outbreak 2013-2016. It is the most advanced EBOV candidate currently in the licensure process. The experimental vaccine was again administered as response to outbreaks in the Democratic Republic of Congo. However, underlying molecular mechanisms that convey protection remain incompletely understood. MicroRNAs (miRNAs) are known key regulators that influence gene expression on a post-transcriptional level. The miRNA-mediated control has emerged as a critical regulatory principle in the immune system, which strongly influences the balance of innate and adaptive immune responses by modulation of signaling pathways critical for differentiation of immune cells. We investigated expression levels of circulating miRNAs (c-miRNAs) in plasma from healthy vaccinees, as they may reflect cellular dynamics following VSV-EBOV immunization and additionally may serve as potential biomarkers for vaccine efficacy. As part of the WHO-led VEBCON consortium, we investigated safety and immunogenicity of VSV-EBOV in a phase I trial. A comprehensive analysis of expression levels on c-miRNAs from plasma samples following VSV-EBOV immunization (day 0, 1, 3 post vaccination) was conducted using RT-qPCR assays. Potential biological relevance was assessed using in silico analyses. Additionally, we correlated dynamics of miRNA expressions with our previously reported data on vaccine-induced antibody and cytokine responses and finally evaluated the prognostic power by generating ROC curves. We identified four promising miRNAs (hsa-miR-146a, hsa-miR-126, hsa-miR-199a, hsa-miR-484), showing a strong association with adaptive immune responses, exhibited favourable prognostic performance and are implicated in immunology-related functions. Our results provide evidence that miRNAs may serve as useful biomarkers for prediction of vaccine-induced immunogenicity. Furthermore, our unique data set provides insight into molecular mechanisms that underlie VSV-EBOV-mediated protective immune responses, which may help to decipher VSV-EBOV immune signature and accelerate strategic vaccine design or personalized approaches.

Time from accident to admission to a burn intensive care unit: how long does it actually take? A 25-year retrospective data analysis from a german burn center.

Severe burn injuries often require specialized treatment at a burn center. It is known that prompt admission to an intensive care unit is essential for achieving good outcome. Nevertheless, very little is known about the duration of time before a patient is admitted to a specialized center after a burn injury in Germany, and whether the situation has improved over time. We retrospectively analyzed time from burn injury to admission to the burn intensive care unit in the Cologne-Merheim Medical Center - one of Germany's specialized burn centers - over the last 25 years. Moreover, we analyzed the data based on differences according to time of injury and day of the week, as well as severity of the burn injury. There was no weekend effect with regard to transfer time; instead transfer time was particularly short on a Monday or on Sundays. Furthermore, patients with severe burn injuries of 40-89% total body surface area (TBSA) showed the least differences in transfer time. Interestingly, the youngest and the oldest patients arrived at the burn intensive care unit (BICU) the fastest. This study should help elucidate published knowledge regarding transfer time from the scene of the accident to admission to a BICU in Germany.

Les brûlés graves ont fréquemment besoin d'une prise en charge spécialisée dans un centre de brûlés (CTB). Il est avéré qu'une admission rapide dans un service de réanimation pour brûlés (SRB) est un paramètre d'évolution favorable. Cependant, on ne sait que peu de chose sur le temps écoulé, en Allemagne, entre la brûlure et l'admission en CTB, et si ce délai s'est raccourci au fil du temps. Nous avons analysé le délai entre brûlure et arrivée dans le SRB de Cologne-Merheim sur une durée de 25 ans. Nous avons aussi étudié l'impact de la gravité de la brûlure, du jour et de l'heure de sa survenue sur ce délai. Il n'y a pas « d'effet week-end ¼, et le délai est plus court les lundis et dimanches. Le délai est relativement homogène pour des surfaces brûlées de 40 à 89%. Les patients les plus jeunes et les plus âgés sont ceux qui arrivent le plus vite en SRB. Cette étude devrait aider à clarifier les données déjà publiées concernant le temps de transfert du lieu de l'accident au SRB en Allemagne.

[A 73-year-old female patient after liver and kidney transplantation with dull pain in the epigastrium and recurrent epistaxis]. / 73-jährige leber- und nierentransplantierte Patientin mit dumpfen Oberbauchschmerzen und rezidivierendem Nasenbluten.

A 73-year-old female patient who had received a liver and kidney transplantation presented with symptomatic pancytopenia and right-sided upper abdominal pain. The histological investigation of a bone marrow biopsy showed the extremely rare manifestation of a disseminated Merkel cell carcinoma with infiltration of the bone marrow and suppression of hematopoiesis. Also a Coombs test positive hemolytic anemia did not show a significant response to high-dose steroid therapy. Palliative chemotherapy with carboplatin and etoposide at reduced dosage had to be terminated due to deterioration of the patient's general condition. The patient died 2 days after initiation of chemotherapy.

Accuracy of peri-implant bone evaluation using cone beam CT, digital intra-oral radiographs and histology.

OBJECTIVES: The present study assesses the accuracy of three-dimensional (3D) cone beam CT (CBCT) and intra-oral radiography (CR) in visualizing peri-implant bone compared with histology. METHODS: 26 titanium dental implants were placed in dog jaws with chronic type vestibular defects. After a healing period of 2 and 8 weeks (n = 12 dogs) the animals were sacrificed. CBCT scans and CR of the specimen were recorded. Dissected blocks were prepared, and histomorphometric analysis was performed. Both modalities were measured twice by two observers and compared with histomorphometry regarding bone levels and thickness around implants as well as length and diameter of implants. RESULTS: Measurements of CBCT correlated well with histomorphometry of the vestibular bone level, oral bone thickness and implant length (all p-values <0.05). Compared with histomorphometry, the mean differences between CBCT and histomorphometry were between 0.06 and 2.61 mm. Mesial bone level (MBL) and distal bone level (DBL) were underestimated by both CR and CBCT. CR and histology measurements were only significantly correlated for implant length measurements. All intraclass correlations were highly significant. CONCLUSIONS: 3D CBCT provides usable information about bone in all dimensions around implants with varying accuracy. CR and CBCT perform similar in assessing MBL and DBL, but, within its limits, the CBCT can assess oral and buccal bone. Metallic artefacts limit the visualization quality of bone around implants and further research could elucidate the value of post-processing algorithms. When information about osseous perforation of implants is needed, CBCT may still provide clinically valuable information.

Bimaxillary 'rotation advancement' procedures in patients with obstructive sleep apnea: a 3-dimensional airway analysis of morphological changes.

The aim of this retrospective three dimensional (3D) computed tomographic analysis was to investigate the morphological airway changes in 17 obstructive sleep apnea (OSA) patients following bimaxillary rotation advancement procedures. Morphological changes of the nasal cavity and naso-, oro- and hypopharynx were analysed separately, as were the total airway changes using nine parameters of airway size and four of shape. The Wilcoxon test was used to compare airway changes and the intraclass correlation coefficient to qualify inter-observer reliability. Following bimaxillary advancement and anti-clockwise maxillary rotation, the total airway volume and the lateral dimension of the cross-sectional airway increased significantly. The total length of the airway became shorter (p<0.05). Remarkable changes were seen in the oropharynx: the length, volume, cross-sectional area (CSA), antero-posterior and medio-lateral distance changed (p<0.05). This combined with a significant 3D change in the shape of the airway from round to elliptical. The average cross-sectional oropharyngeal area was nearly doubled, the minimal CSA increased 40%, and the hyoid bone was located more anterior and superior. Inter-examiner reliabilities were high (0.89). 3D airway analysis aids the understanding of postoperative pathophysiological changes in OSA patients. The airway became shorter, more voluminous, medio-laterally wider, and more compact and elliptical.

Liver transplantation in a patient with developmental interruption of the inferior vena cava with azygos substitution.

Infrahepatic interruption of the inferior vena cava (IVC) with azygos or hemiazygos substitution has been reported frequently in children with biliary atresia where this venous abnormality is associated with other venous abnormalities such as preduodenal portal vein or congenital heart disease. It is important to recognize this anomaly pretransplant because the hepatic vein may drain directly into the right atrium rather than into the suprahepatic vena cava. We describe herein the first report of an orthotopic deceased donor liver transplant in an adult patient with an interrupted IVC and azygos continuation. We also review the embryological development of the IVC and the vascular anomalies that can occur.

Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis.

OBJECTIVE: To explore whether high-dose atorvastatin can be administered safely to persons with relapsing-remitting multiple sclerosis (MS) taking thrice weekly, 44 microg dose subcutaneous interferon beta-1a. METHODS: Persons with clinically stable, relapsing-remitting MS, on standard high-dose subcutaneous interferon beta-1a, were randomized in a double-blind fashion to receive either placebo or atorvastatin at dosages of 40 or 80 mg/day for 6 months. Blinded neurologic examinations and brain MRI readings were obtained at months 0, 3, 6, and 9. Laboratory blood testing was performed monthly. Main outcome measures were the determination of drug toxicity using blood tests and ECG and determination of MS-related disease activity, either clinical relapses or new or contrast-enhancing lesions on MRI. RESULTS: Twenty-six subjects received at least one dose of study drug. Ten of 17 subjects on either 80 mg or 40 mg of atorvastatin per day had either new or enhancing T2 lesions on MRI or clinical relapses. One of the nine subjects on placebo had a relapse with active lesions on MRI. The subjects receiving atorvastatin were at greater risk for either clinical or MRI disease activity compared to placebo (p = 0.019). Significant changes in blood tests were noted only for lower cholesterol levels in subjects receiving atorvastatin. CONCLUSION: The combination of 40 or 80 mg atorvastatin with thrice weekly, 44 microg interferon beta-1a in persons with multiple sclerosis resulted in increased MRI and clinical disease activity. Caution is suggested in administering this combination.

Intraoperative navigation in the maxillofacial area based on 3D imaging obtained by a cone-beam device.

The aim of this study was to evaluate intraoperative navigation in the maxillofacial area based on three-dimensional imaging obtained by a cone-beam device. Digital volume tomograms (DVT) were obtained by the prototype of GALILEOS (Sirona Dental Systems Inc., Bensheim, Germany), a newly developed, compact size, cone-beam machine with a scan volume of 15 cm x 15 cm x 15 cm. Intraoperative navigation was performed in 12 patients in three selected indications. Target detection error expressing the accuracy of DVT navigation and registration performance of specially developed methods for image-to-patient registration was estimated. Target detection error was maximally 2 mm and depended on the registration method chosen. The automatic detection rate of the fiducial markers ranged between 0.64 and 0.32. The preoperatively defined treatment plan was fully accomplished in 11 out of 12 cases. A favourable surgical outcome was achievable in all cases. Intraoperative complications were not observed. Intraoperative navigation based on DVT imaging can be considered as a valuable alternative to CT-based procedures. Special characteristics of the cone-beam technique, in terms of contrast resolution and the limited field-of-view size of the devices, restrict the indication spectrum and create a demand for modifications of the usual registration methods.

Comparison of static and dynamic computer-assisted guidance methods in implantology.

The planning of dental implant position and its transfer to the operation site can be considered as one of the most important factors for the long-term success of implant-supported prosthetic and epithetic restorations. This study compares computer-assisted fabricated surgical templates as the static method with intro-operative image guided navigation as the dynamic method for transfer of three-dimensional pre-operative planning. For the static method, the systems Med3D, coDiagnostix/ gonyX, and SimPlant were used. For the dynamic method, the systems RoboDent und VectorVision2 were applied. A total of 746 implants were inserted between August 1999 and December 2005 in 206 patients. The static approach was used most frequently, accounting for 611 fixtures in 168 patients. The failure ratios within the first 6 months were 1.31% in the statically controlled insertion group compared to 2.96% in the dynamically controlled insertion group. Complications related to an incorrect position of the implants have not been observed so far in either group. All computer-assisted methods included in this study were successfully applied in a clinical setting after a certain start-up period. The indications for application of computer-assisted methods in implantology are currently given in difficult anatomical situations. Due to uncomplicated handling and low resource demands, the static template technique can be recommended as the method of choice for the majority of all cases falling into this category.

Isolation and identification of an ice-nucleating bacterium from the gills of the intertidal bivalve mollusc Geukensia demissa.

In the fall, freeze tolerant intertidal invertebrates usually produce ice-nucleating proteins that are secreted into the hemolymph. These proteins help protect against freeze damage by insuring that ice formation is limited to extracellular spaces. Geukensia demissa, a freeze tolerant, salt marsh bivalve mollusc was examined for the presence of ice nucleating proteins. The ice-nucleating temperature (INT) of the hemolymph was not significantly different from artificial seawater of the same salinity indicating the lack of an ice nucleating protein in the hemolymph. The palial fluid did have an elevated INT, indicating the presence of an ice nucleator. The INT of the palial fluid was significantly reduced by boiling and filtration through a 0.45-&mgr;m filter. High INT was also observed in the seawater associated with the bivalves, and was demonstrated in water samples collected from salt marshes but not sand and pebble beaches. Moreover, the INT of water samples collected from a salt marsh decreased in the summer. All of these data suggest that the ice-nucleating agents in the hemolymph and the seawater are ice-nucleating bacteria. One species of ice-nucleating bacteria, Pseudomonas fulva was isolated from the gills of Geukensia. These bacteria could perform the same function as hemolymph ice-nucleating proteins by limiting ice formation to extracellular compartments.

A longitudinal study of high scorers on the hypomanic personality scale.

Former college students (n = 36) identified by high scores on the Hypomanic Personality Scale (HYP; Eckblad & Chapman, 1986) were compared with control participants (n = 31) at a 13-year follow-up assessment. As hypothesized, the HYP group reported more bipolar disorders and major depressive episodes than the control group. The HYP group also exceeded the control group on the severity of psychotic-like experiences, symptoms of borderline personality disorder, and rates of substance use disorders. HYP group members with elevated scores on the Impulsive-Nonconformity Scale (Chapman et al., 1984) experienced greater rates of bipolar mood disorders, poorer overall adjustment, and higher rates of arrest than the remaining HYP or control participants.

Manipulating smoking motivation: impact on an electrophysiological index of approach motivation.

A chief goal of this research was to determine whether stimuli and events known to enhance smoking motivation also influence a physiological variable with the potential to index approach motivation. Asymmetry of electroencephalographic (EEG) activity across the frontal regions of the 2 hemispheres (left minus right hemisphere activation) was used to index approach motivation. In theory, if EEG asymmetry sensitively indexes approach dispositions, it should be influenced by manipulations known to affect smoking motivation, that is, exposure to smoking cues and tobacco deprivation. Seventy-two smokers participated in this research and were selectively exposed to a smoking-anticipation condition (cigarettes plus expectation of imminent smoking) following either 24 hr of tobacco withdrawal or ad libitum smoking. Results indicated that EEG asymmetry was increased by smoking anticipation and that smoking itself reduced EEG asymmetry. Results also suggested that smoking anticipation increased overall (bihemispheric) EEG activation. Results were interpreted in terms of major theories of drug motivation.

Magical ideation and social anhedonia as predictors of psychosis proneness: a partial replication.

The authors compared college students identified by high scores on the Magical Ideation Scale (M. Eckblad & L. J. Chapman, 1983) and the Revised Social Anhedonia Scale (MagSoc; n = 28; M. Eckblad, L. J. Chapman, J. P. Chapman, & M. Mishlove, 1982) with control participants (n = 20) at a 10-year follow-up assessment in an attempt to replicate L. J. Chapman, J. P. Chapman, T. R. Kwapil, M. Eckblad, and M. C. Zinser's (1994) report of heightened psychosis proneness in MagSoc individuals. The MagSoc group exceeded the control group on severity of psychotic-like experiences; ratings of schizotypal, paranoid, and borderline personality disorder symptoms; and rates of mood and substance use disorders. Two of the MagSoc participants but none of the control participants developed psychosis during the follow-up period (a nonsignificant difference). Consistent with L. J. Chapman et al.'s findings, the groups did not differ on rates of personality disorders or relatives with psychosis.

Putatively psychosis-prone subjects 10 years later.

The predictive validities of several indicators of psychosis proneness were evaluated in a 10-year longitudinal study (N = 508). As hypothesized, high scorers on the Perceptual Aberration Scale, Magical Ideation Scale, or both (n = 182), especially those who initially reported psychoticlike experiences of at least moderate deviance, exceeded control subjects (n = 153) on psychoses (revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders), psychotic relatives, schizotypal symptoms, and psychoticlike experiences at follow up. Ss who initially scored high on the Magical Ideation Scale and above the mean on the Social Anhedonia Scale were especially deviant. The Physical Anhedonia Scale and the Impulsive Nonconformity Scale were not effective predictors of psychosis proneness.

Relation between self-reported affect and drug urges and cravings in continuing and withdrawing smokers.

In 2 experiments we investigated the effects of withdrawal and stress on the affective correlates of urges to smoke. In both, habitual cigarette smokers were divided into continuing and withdrawing smoker groups. In the 1st study, 44 adults reported current mood, urge, and expectations over a 24-hr period. In the 2nd, a controlled laboratory study, urge, affect, and physiological data were obtained from continuing and withdrawing groups (N = 64) exposed to high- or low-stress conditions. Urges among withdrawing smokers were positively associated with negative affect and negatively associated with positive affect; continuing smokers reported urges that were directly associated with positive affect and unrelated to negative affect. Stress and withdrawal produced urge self-reports that were related to negative affect. Moreover, subjects who smoked after exposure to withdrawal and stress reported greater pleasure and arousal than did other subjects.

Subjective dimensions of heroin urges: influence of heroin-related and affectively negative stimuli.

Thirty-five male drug-free heroin addicts rated their affect, craving, and withdrawal in response to boring, anxiety-eliciting, and heroin stimuli. Results revealed that: (a) heroin cues were more effective than boring or anxiety-eliciting cues in prompting self-reports of craving or withdrawal; (b) heroin cues produced an affective state characterized by self-reported low-pleasure and high anxiety/tension; (c) craving was not correlated with any particular affective state, but rather was associated with a variety of negative affects--anxiety, depression, fatigue, anger; (d) the coherence (intercorrelations) of affective, craving, and withdrawal measures was greatest when addicts made their self-ratings immediately after exposure to drug stimuli; and (e) while addicts routinely reported craving without withdrawal sickness, they virtually never reported withdrawal sickness without reporting craving. These results suggested that the potential for negative reinforcement subserved stimulus elicited craving and that craving involved cognitive appraisal processes (attributions, expectations).

Sensory blockade of smoking satisfaction.

Cigarette smokers were presented with controlled doses of cigarette smoke to determine whether the resulting reduction in cigarette craving depended upon perceiving the sensory qualities of the smoke. Cigarette craving was assessed before and after inhaling controlled doses of smoke in two conditions: (1) Local anesthesia of the upper and lower respiratory airways, induced by mouth rinsing, gargling and inhalation of a mist containing the topical anesthetic lidocaine; and (2) no-anesthesia control, in which all solutions were saline. A sham smoking procedure was presented in both conditions. Craving and ad lib smoking behavior were also assessed 30 minutes after controlled smoking. The results indicated that smoke, as opposed to sham puffs, significantly reduced reports of cigarette craving, and local anesthesia significantly blocked this immediate reduction in craving produced by smoke inhalation. Puffs were also rated as less desirable in the anesthesia condition. Thirty minutes after smoking, craving was no different in the anesthesia and saline control conditions. However, craving as well as smoking intake in both conditions was less when smoke had been given previously than in the sham smoking control. These results suggest that sensory cues accompanying inhalation of cigarette smoke are important determinants of immediate smoking satisfaction. However, the sustained effects of smoke intake on subsequent smoking behavior (30 min later) may be mediated by processes other than sensory stimulation of the respiratory tract, such as plasma nicotine levels.