Multi-angle in situ dynamic light scattering at a neutron spin echo spectrometer.

A new sample environment, called Bio-Oven, has been built for the Neutron Spin Echo (NSE) Spectrometer J-NSE Phoenix. It provides active temperature control and the possibility to perform Dynamic Light Scattering (DLS) measurements during the neutron measurement. DLS provides diffusion coefficients of the dissolved nanoparticles, and thus one can monitor the aggregation state of the sample on a time scale of minutes during the spin echo measurement times on the order of days. This approach helps to validate the NSE data or to replace the sample when its aggregation state influences the spin echo measurement results. The new Bio-Oven is an in situ DLS setup based on optical fibers decoupling the free space optics around the sample cuvette in a lightproof casing from the laser sources and the detectors. It collects light from three scattering angles simultaneously. Six different values of momentum transfer can be accessed by switching between two different laser colors. Test experiments were performed with silica nanoparticles with diameters ranging from 20 nm up to 300 nm. Their hydrodynamic radii were determined from DLS measurements and compared with the ones obtained by a commercial particle sizer. It was demonstrated that also the static light scattering signal can be processed and gives meaningful results. The protein sample apomyoglobin was used for a long-term test and in a first neutron measurement using the new Bio-Oven. The results prove that the aggregation state of the sample can be followed using in situ DLS along with the neutron measurement.

Material properties and bioactivity of a resin infiltrant functionalized with polyhedral oligomeric silsesquioxanes.

OBJECTIVES: To investigate the effect of methacrylate polyhedral oligomeric silsesquioxanes (POSS-8) on various material properties and mineral precipitation potential of a resin infiltrant. METHODS: A TEGDMA-based resin infiltrant was mixed with 0.5, 1, 3, 5 or 10 wt% POSS-8 or left unchanged (control). Degree of conversion (DC), water sorption (WS), viscosity, elastic modulus (E-modulus), flexural strength (FS), Knoop microhardness (KHN) and softening ratio (SR) were assessed. Growth of calcium phosphate (Ca/P) precipitates infiltrant-treated bovine enamel and dentin specimens immersed in artificial saliva or artificial dentinal fluid, respectively, for 28 days was analyzed by scanning electron microscopy and energy-dispersive X-ray spectroscopy. For viscosity assessment, pure TEGDMA filled with 0-10 wt% POSS-8 was used. Statistical analyses were performed using ANOVA and Tukey's post-hoc tests (p < 0.05). RESULTS: POSS-8 did not change the flexural strength, water sorption and softening ratio. The apparent degree of conversion was increased at lower concentrations only while E-modulus remained constant in almost all groups. The particles led to a slight decrease of KHN at concentrations below 3%. The effect on viscosity is comparable to the reinforcement effect. Ca/P precipitates formed on dentin specimens treated with POSS-8-filled infiltrant after 4 weeks of immersion, but were not detected on the control infiltrant. The mineral precipitation on enamel was not improved by POSS-8. SIGNIFICANCE: POSS-8 particles did not worsen the material properties of the resin infiltrant, while the Ca/P precipitation on dentin was stimulated.

The impact of micronized progesterone on cardiovascular events - a systematic review.

Biologically identical menopausal hormone therapy (MHT) including micronized progesterone (MP) has gained much attention. We aimed to assess the impact of MP in combined MHT on venous and arterial thromboembolism (VTE/ATE) (e.g. deep venous thrombosis/pulmonary embolism, myocardial infarction [MI] and ischemic stroke). Articles were eligible if they provided endpoints regarding cardiovascular events and use of exogenous MP. Literature searches were designed and executed for the databases Medline, Embase, CINAHL, the Cochrane Library, ClinicalTrials.gov and interdisciplinary database Web of Science. Twelve studies consisting of randomized controlled trials (RCTs), case-control studies and prospective or retrospective cohort studies were included, and risk of bias was assessed. Only a minority assessed thromboembolic events as a primary endpoint, showing that in contrast to norpregnane derivatives, primary and recurrent VTE risk was not altered by combining estrogens with MP, which was also true for ischemic stroke risk. Similarly, in placebo-controlled RCTs assessing VTE/ATE as adverse events there were no significant intergroup differences. Studies on MI as a primary endpoint are missing. In conclusion, while available data suggest that MP as a component in combined MHT may have a neutral effect on the vascular system, more RCTs investigating the impact of MP alone or in combined MHT on vascular primary endpoints are needed.

High-Resolution Gadolinium-Enhanced MR Cisternography Using Compressed-Sensing T1 SPACE Technique for Detection of Intracranial CSF Leaks.

In patients with CSF rhinorrhea, accurate identification of the CSF leakage site is crucial for surgical planning. We describe the application of a novel gadolinium-enhanced high-resolution 3D compressed-sensing T1 SPACE technique for MR cisternography and compare findings with CT cisternography and intraoperative results. In our pilot experience with 7 patients, precise detection of CSF leaks was feasible using compressed-sensing T1 SPACE, which appeared to be superior to CT cisternography.

The impact of menopausal hormone therapy on overall mortality - a comprehensive review.

Menopausal hormone therapy (MHT) is indicated for menopausal symptom relief. However, MHT has also been shown to be beneficial for prevention of long-term estrogen deficiency sequelae including mortality. Based on a comprehensive literature review on MHT and mortality, the authors' recommendations are as follows: in postmenopausal women, MHT appears to confer a (significant) reduction in overall mortality; the benefit especially applies to women who initiate long-term MHT early after menopause; in women with prevalent cardiovascular risk factors (except for diabetes mellitus, where results are mixed), the benefit of MHT on overall mortality is even more pronounced; and, however, study results are difficult to compare due to heterogeneous study designs.

Impact of endogenous and exogenous progesterone exposure on stress biomarkers: a systematic review.

Stress activates the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal axis (HPAA). Based on a systematic literature review of the impact of endogenous and exogenous exposure with natural progesterone on the stress response in healthy premenopausal and postmenopausal women, the following conclusions can be drawn: the HPAA activity was not relevantly affected by endogenous progesterone exposure across the menstrual cycle, but might be reduced by exogenous micronized progesterone application; in contrast, the ANS has a sympathetic predominance in the (progesterone-dominated) luteal phase of the menstrual cycle. Future studies should assess various stress biomarkers under various hormonal conditions to, for example, allow for cardiovascular risk stratification in hormone users.

Impacts of supragingival and subgingival periodontal treatments on oral health-related quality of life.

OBJECTIVE: The aim of this study was to evaluate the impact of distinct phases of a non-surgical periodontal treatment protocol on oral health-related quality of life (OHRQoL). METHODS: Fifty-five participants (51.4 ± 9.4 years), diagnosed with both gingivitis and moderate-to-severe periodontitis, were included. Periodontal and OHRQoL (OHIP-14) data were collected before (Day 0) and after the supragingival (Day 30) and subgingival (Day 90) treatments. A linear mixed model was used. OHIP-14 scores, effect size, and ceiling and floor effects were calculated. RESULTS: The total OHIP-14 score was significantly higher at Day 0 (17.3 ± 10.5) compared to Day 30 (9.7 ± 8.3) and Day 90 (9.5 ± 7.4). Scores of all domains decreased significantly after the supragingival treatment. This response was maintained after the subgingival therapy, except in the physical pain and physical disability domains. Clinical variables were not associated with the change in OHIP scores. The effect size was 0.72 at Day 30 and 0.74 at Day 90. No ceiling and floor effect were observed. CONCLUSIONS: Perceptions on OHRQoL improved along periodontal therapy, particularly after the supragingival treatment, suggesting that this intervention might be considered important to reduce the negative impacts in oral health-related quality of life.

"Heidelberg standard examination" and "Heidelberg standard procedures" - Development of faculty-wide standards for physical examination techniques and clinical procedures in undergraduate medical education.

The competent physical examination of patients and the safe and professional implementation of clinical procedures constitute essential components of medical practice in nearly all areas of medicine. The central objective of the projects "Heidelberg standard examination" and "Heidelberg standard procedures", which were initiated by students, was to establish uniform interdisciplinary standards for physical examination and clinical procedures, and to distribute them in coordination with all clinical disciplines at the Heidelberg University Hospital. The presented project report illuminates the background of the initiative and its methodological implementation. Moreover, it describes the multimedia documentation in the form of pocketbooks and a multimedia internet-based platform, as well as the integration into the curriculum. The project presentation aims to provide orientation and action guidelines to facilitate similar processes in other faculties.

Fast internal dynamics in alcohol dehydrogenase.

Large-scale domain motions in alcohol dehydrogenase (ADH) have been observed previously by neutron spin-echo spectroscopy (NSE). We have extended the investigation on the dynamics of ADH in solution by using high-resolution neutron time-of-flight (TOF) and neutron backscattering (BS) spectroscopy in the incoherent scattering range. The observed hydrogen dynamics were interpreted in terms of three mobility classes, which allowed a simultaneous description of the measured TOF and BS spectra. In addition to the slow global protein diffusion and domain motions observed by NSE, a fast internal process could be identified. Around one third of the protons in ADH participate in the fast localized diffusive motion. The diffusion coefficient of the fast internal motions is around two third of the value of the surrounding D2O solvent. It is tempting to associate the fast internal process with solvent exposed amino acid residues with dangling side chains.

Medical preparedness, incidents, and group dynamics during the analog MARS2013 mission.

Participants on spaceflights and international scientific analog Mars missions can encounter medical incidents (accidents, illnesses) and psychological issues (e.g., stress, group interaction, sleep disturbance, emotions). The aim of this study was to examine these parameters in a field crew living in a desert environment similar to Mars (Group 1) and in Mission Support Center (MSC) personnel on "Earth" (Group 2) during a 4-week mission. Of the 107 medical interventions in the field, 73 mainly minor incidents together with four near accidents and 29 medical checkup interventions were recorded. Of the 32 medical interventions, medical treatments for 23 incidents of minor severity were necessary in Group 2. Injuries (Group 1: 1.4/100 h, Group 2: 0.1/100 h) were significantly increased in the field, and illnesses (Group 1: 0.3/100 h, Group 2: 3.0/100 h) in the MSC personnel. Causes of accidents and illnesses are described. Psychological results show that emotions and stress remained stable in both groups. Sympathy, social competence, teamwork, and leadership showed high scores. These scores were lower on "Earth" but significantly increased in the last weeks. The Sahara's nighttime coldness was reflected in an increased wake-up frequency, and a longer sleeping time peaked in the third week, probably as a result of overfatigue. MARS2013 was a successful mission with highly motivated participants and minor medical incidents. For future analog missions and possibly long-distance open-space missions, some recommendations in terms of medical and psychological preparedness are made to reduce risks for field crew members and MSC personnel.

The role of dual energy CT in differentiating between brain haemorrhage and contrast medium after mechanical revascularisation in acute ischaemic stroke.

OBJECTIVES: To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. METHODS: Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as "conventional CT", and DE-CT interpretations were evaluated and compared with follow-up CT. RESULTS: Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. CONCLUSIONS: Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. KEY POINTS: • Contrast material and haemorrhage have similar density on conventional 120-kV CT. • Contrast material hinders interpretation of CT in stroke patients after recanalisation. • Iodine and haemorrhage have different attenuation at lower kVs. • Dual energy CT improves accuracy in early differentiation of haemorrhage and contrast extravasation. • Early differentiation between iodine and haemorrhage helps to initiate therapy promptly.

Flow behavior of fetal, neonatal and adult RBCs in narrow (3-6 µm) capillaries--Calculation and experimental application.

BACKGROUND AND OBJECTIVES: In capillaries with diameters less than those of resting RBCs, the cells have to deform to pass through such narrow vessels. Since RBCs of fetuses, neonates and adults differ in their geometrical properties the flow behavior of RBCs with different sizes in uniform tubes with diameters of 3 to 6 µm were studied by means of a micropipette system and a mathematical model. Assumptions in this model include an RBC flow velocity of 1 mm/s, axisymmetric cell shape and a gap between the RBC and the vessel wall that allows sufficient lubrication. The flow resistance depends on the surface area and volume of RBCs, the plasma viscosity and the vessel diameter. METHODS: Surface area and volume of different RBC populations (20 fetuses, 20 preterm neonates, 10 term neonates and 10 adults) were determined by means of a micropipette system and plasma viscosity was measured using a capillary tube viscometer. The flow behavior of RBCs with different volumes (61, 83 and 127 fl) was studied by direct microscopic observation using a micropipette system. The micropipettes had diameters of 3.5, 4.1, 5.1, and 6.0 µm. The flow velocity of the RBC in the pipettes was 1 mm/s and the calculated and measured cell lengths were compared. RESULTS: Volume and surface area of RBCs were 140 ± 29 fl and 172 ± 20 µm2, respectively, in the fetuses, decreased with increasing maturity (term neonates: 110 ± 20 fl and 149 ± 18 µm2) and reached the lowest values in adults (93 ± 14 fl and 136 ± 12 µm2). Plasma viscosities increased with increasing maturity due to rising plasma protein concentrations. The flow model leads to the following conclusions: During the passage of 3- to 6-µm vessels, the large fetal and neonatal RBCs are more elongated than the smaller adult RBCs. The critical vessel diameter, i.e., when the rear of the RBC becomes convex during passage of a narrow capillary, was 4.1 µm for fetal RBCs, 3.6 µm for neonatal RBCs and 3.3 µm adult cells. Suspended in the same medium, fetal and neonatal RBCs require 27% (term neonates) to 100% (fetuses) higher driving pressures than adult RBCs to achieve the necessary elongation for passing through a 4.5-µm capillary. However, the different RBCs require similar driving pressures if the cells are suspended in the corresponding autologous plasma. Cell lengths of the RBCs with different geometry determined during the flow experiments agreed with the predicted values. CONCLUSION: We conclude that the large size of fetal and neonatal RBCs may cause impaired flow in narrow vessels with diameters below the critical values of 3.6 to 4.1 µm. In vessels with diameters above the critical diameter (Dcr), the disadvantage of the large size of neonatal and fetal RBCs appears to be completely compensated for by the lower plasma viscosity.

[First-trimester cystic hygroma: prenatal diagnosis and fetal outcome]. / Hygroma kystique découvert à l'échographie obstétricale du 1er trimestre : caractéristiques échographiques, caryotypiques et devenir de la grossesse.

OBJECTIVES: To describe the ultrasonographic (US) and fetal karyotyping data of fetuses with cystic hygroma diagnosed in the first trimester. PATIENTS & METHODS: Maternal and fetal data of 69 consecutive fetal cystic hygroma were analysed between 2002 and 2009. RESULTS: The mean size of the cystic hygroma was 6.3 mm ± 2.4 mm. US abnormalities were present in 54% of cases (37/69) (essentially hydrops fetalis in 45%), with an unfavourable prognosis (P=0.006). Chromosomal abnormalities were present in 53% of cases (36/68) (including 44% of Down syndrome). The rate of unfavourable outcome of pregnancy was 71% of cases (49/69) and was associated with the oldest mothers (P=0.011). In the chromosomally normal pregnancies, there were 59% (19/32) fetus with no apparently abnormalities. Among these 19 children, 13 have been followed up until an average age of 5 years and a half, the infant development was strictly normal. DISCUSSION AND CONCLUSION: The current results suggest to look for the poor prognosis data: nuchal thickness superior to 6 to 6,5 mm, presence of a hydrops fetalis and/or US abnormalities, fetal karyotyping and/or US evolution of cystic hygroma.

Multiplanar reconstruction computed tomography for diagnosis of scaphoid waist fracture union: a prospective cohort analysis of accuracy and precision.

OBJECTIVE: To examine reliability and validity concerning union of scaphoid fractures determined by multiplanar reconstruction computed tomography randomized at 6, 12, and 24 weeks after injury. MATERIALS AND METHODS: We used Fleiss' kappa to measure the opinions of three observers reviewing 44 sets of computed tomographic scans of 44 conservatively treated scaphoid waist fractures. We calculated kappa for the extent of consolidation (0-24 %, 25-49 %, 50-74 %, or 75-100 %) on the transverse, sagittal and coronal views. We also calculated kappa for no union, partial union, and union, and grouped the results for 6, 12, and 24 weeks after injury. As the reference standard for union, CT scans were performed at a minimum of 6 months after injury to determine validity. RESULTS: Overall inter-observer agreement was found to be moderate (κ = 0.576). No union (κ = 0.791), partial union (κ = 0.502), and union (κ = 0.683) showed substantial, moderate, and substantial agreement, respectively. The average sensitivity of multiplanar reconstruction CT for diagnosing union of scaphoid waist fractures was 73 %. The average specificity was 80 %. CONCLUSIONS: Our results suggest that multiplanar reconstruction computed tomography is a reliable and accurate method for diagnosing union or nonunion of scaphoid fractures. However, inter-observer agreement was lower with respect to partial union.

Thermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics.

Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the ß-subunits.

From powder to solution: hydration dependence of human hemoglobin dynamics correlated to body temperature.

A transition in hemoglobin (Hb), involving partial unfolding and aggregation, has been shown previously by various biophysical methods. The correlation between the transition temperature and body temperature for Hb from different species, suggested that it might be significant for biological function. To focus on such biologically relevant human Hb dynamics, we studied the protein internal picosecond motions as a response to hydration, by elastic and quasielastic neutron scattering. Rates of fast diffusive motions were found to be significantly enhanced with increasing hydration from fully hydrated powder to concentrated Hb solution. In concentrated protein solution, the data showed that amino acid side chains can explore larger volumes above body temperature than expected from normal temperature dependence. The body temperature transition in protein dynamics was absent in fully hydrated powder, indicating that picosecond protein dynamics responsible for the transition is activated only at a sufficient level of hydration. A collateral result from the study is that fully hydrated protein powder samples do not accurately describe all aspects of protein picosecond dynamics that might be necessary for biological function.

From shell to cell: neutron scattering studies of biological water dynamics and coupling to activity.

An integrated picture of hydration shell dynamics and of its coupling to functional macromolecular motions is proposed from studies on a soluble protein, on a membrane protein in its natural lipid environment, and on the intracellular environment in bacteria and red blood cells. Water dynamics in multimolar salt solutions was also examined, in the context of the very slow water component previously discovered in the cytoplasm of extreme halophilic archaea. The data were obtained from neutron scattering by using deuterium labelling to focus on the dynamics of different parts of the complex systems examined.