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.

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.

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.

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.

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.

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.

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.

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.

Dynamics of apomyoglobin in the alpha-to-beta transition and of partially unfolded aggregated protein.

Changes of molecular dynamics in the alpha-to-beta transition associated with amyloid fibril formation were explored on apomyoglobin (ApoMb) as a model system. Circular dichroism, neutron and X-ray scattering experiments were performed as a function of temperature on the protein, at different solvent conditions. A significant change in molecular dynamics was observed at the alpha-to-beta transition at about 55 degrees C, indicating a more resilient high temperature beta structure phase. A similar effect at approximately the same temperature was observed in holo-myoglobin, associated with partial unfolding and protein aggregation. A study in a wide temperature range between 20 and 360 K revealed that a dynamical transition at about 200 K for motions in the 50 ps time scale exists also for a hydrated powder of heat-denatured aggregated ApoMb.

Hemoglobin senses body temperature.

UNLABELLED: When aspirating human red blood cells (RBCs) into 1.3 mum pipettes (DeltaP = -2.3 kPa), a transition from blocking the pipette below a critical temperature T(c) = 36.3 +/- 0.3 degrees C to passing it above the T(c) occurred (micropipette passage transition). With a 1.1 mum pipette no passage was seen which enabled RBC volume measurements also above T(c). With increasing temperature RBCs lost volume significantly faster below than above a T(c) = 36.4 +/- 0.7 (volume transition). Colloid osmotic pressure (COP) measurements of RBCs in autologous plasma (25 degrees C < or = T < or = 39.5 degrees C) showed a T (c) at 37.1 +/- 0.2 degrees C above which the COP rapidly decreased (COP transition). In NMR T(1)-relaxation time measurements, the T(1) of RBCs in autologous plasma changed from a linear (r = 0.99) increment below T(c) = 37 +/- 1 degrees C at a rate of 0.023 s/K into zero slope above T(c) (RBC T(1) transition). IN CONCLUSION: An amorphous hemoglobin-water gel formed in the spherical trail, the residual partial sphere of the aspirated RBC. At T(c), a sudden fluidization of the gel occurs. All changes mentioned above happen at a distinct T(c) close to body temperature. The T(c) is moved +0.8 degrees C to higher temperatures when a D(2)O buffer is used. We suggest a mechanism similar to a "glass transition" or a "colloidal phase transition". At T(c), the stabilizing Hb bound water molecules reach a threshold number enabling a partial Hb unfolding. Thus, Hb senses body temperature which must be inscribed in the primary structure of hemoglobin and possibly other proteins.

Hemoglobin dynamics in red blood cells: correlation to body temperature.

A transition in hemoglobin behavior at close to body temperature has been discovered recently by micropipette aspiration experiments on single red blood cells (RBCs) and circular dichroism spectroscopy on hemoglobin solutions. The transition temperature was directly correlated to the body temperatures of a variety of species. In an exploration of the molecular basis for the transition, we present neutron scattering measurements of the temperature dependence of hemoglobin dynamics in whole human RBCs in vivo. The data reveal a change in the geometry of internal protein motions at 36.9 degrees C, at human body temperature. Above that temperature, amino acid side-chain motions occupy larger volumes than expected from normal temperature dependence, indicating partial unfolding of the protein. Global protein diffusion in RBCs was also measured and the findings compared favorably with theoretical predictions for short-time self-diffusion of noncharged hard-sphere colloids. The results demonstrated that changes in molecular dynamics in the picosecond time range and angstrom length scale might well be connected to a macroscopic effect on whole RBCs that occurs at body temperature.

"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.

[Fractures of the atlantoaxial complex in the elderly: assessment of radiological spectrum of fractures and factors influencing imaging diagnosis]. / Frakturen des Atlas und Axis bei älteren Patienten: Untersuchung des Radiologischen Spektrums der Frakturen und bedeutsamer Faktoren für die Bildgebende Diagnostik.

OBJECTIVE: To describe patterns of atlantoaxial fractures in a population of consecutive elderly patients, including assessment of type, distribution and associated clinical and radiological findings, and to analyze any influence of the causative trauma mechanism on the individual fracture pattern. MATERIALS AND METHODS: The distribution and type of 123 atlantoaxial fractures in 95 subjects older than 65 years (range: 65 - 102; mean age: 79 years) were retrospectively assessed. For each subject, trauma mechanism and clinical and neurological status were recorded at admission. Initial imaging studies of the cervical spine were reviewed. Preexistent degenerative changes were assessed and the atlantoaxial fractures classified. Data were evaluated for the frequency of different types of fractures of C1 and C2 and for accompanying fractures of cervical vertebrae or the occipital condyles, respectively. RESULTS: The majority of patients with injuries of the atlantoaxial complex had fractures of C2 (90 of 95, 95 %). A large proportion of these patients (67 of 90, 74 %) had odontoid fractures. An isolated fracture of C1 was present in only 5 (5 %) patients. Associated fractures of the occipital condyles or other cervical vertebrae were rare (10 of 95, 11 %). The main trauma mechanism for atlantoaxial injuries was a fall (56 of 95, 59 %). Elderly patients injured in motor vehicle accidents were more likely to have isolated fractures of C2 and Type III fractures of the odontoid (p < 0.02). CONCLUSION: In elderly patients, fractures of the atlantoaxial complex are mainly caused by falls and almost always involve C2. The trauma mechanism influences the fracture pattern.

Blood viscosity and optimal hematocrit in narrow tubes.

Blood viscosity in normal adults was measured in glass tubes with diameters of 50, 100 and 500 microns for a wide range of adjusted feed hematocrits (15-70%). Blood viscosity decreased at each of the adjusted feed hematocrits when going from a 500-micron tube to a 50-micron tube. The viscosity reduction increased with increasing hematocrit. The steepness in the hematocrit-viscosity curves decreased with decreasing tube diameter. Erythrocyte transport efficiency (hematocrit/blood viscosity) was calculated to estimate the optimal hematocrit for oxygen transport. Optimal hematocrit averaged 38% in 500-micron tubes, 44% in 100-micron tubes and 51% in 50-micron tubes. Our results suggest that the strong Fåhraeus-Lindqvist effect at high hematocrits may help to maintain oxygen transport in polycythemic patients as long as the driving pressure is sufficient.

Salmonella enteritidis colonization in turkey poults.

An experimental trial on the colonization of two Salmonella enteritidis strains (phage types 4 and 8) originating from meat turkey flocks, were carried out. Three-day old poults were inoculated orally with approximately 10(6) cfu/bird (one group with PT8 and the other with PT4). clinical signs were not observed in any of the groups. The total reisolation rates from cloacal swabs in birds inoculated with PT4 was higher than from birds inoculated with PT8. The inoculated strains could also be detected in contact birds. Examination of internal organs 21 days p.i. revealed higher isolation rates in the group infected with PT4 than with PT8. The results indicate that both phage types of S. enteritidis were able to colonize the intestinal tract and the internal organs of turkey poults. However, the colonization and duration of shedding differed between the two phage types. This may be due to the fact that PT8 strain used was free from the S. e. virulence plasmid 37 MDa.

Surveillance on Salmonella in turkey flocks and processing plants.

The present investigation was carried out to investigate the occurrence and distribution of Salmonella infection on all stages of turkey production. Therefore, samples from turkey parent flocks, hatchery, meat turkey flocks, turkey feed and finally from the surveillanced flocks at different steps in processing plant were examined. Salmonella was isolated from 4 out of 6 turkey parent flocks (66.7%), but none of the examined 485 samples from the hatchery revealed positive Salmonella results. Eight out of 24 monitored meat turkey flocks were free from Salmonella during the entire rearing period (33.3%); seven flocks (29.2%) appeared to be infected with only one serovar and in another 9 flocks (37.5%) two or more different serovars were isolated during the rearing period, in some cases at the same time. In 20 out of 506 examined feed samples Salmonella was isolated (3.95%). During processing, bacteriological investigations on the presence of Salmonella were carried out on the monitored flocks at different processing steps. Cross contamination seems to be very common during processing and even in several flocks contamination appeared to have started already during transport.

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.