Exposure to xenoestrogens alters the expression of key morphoregulatory proteins of oviduct adenogenesis in the broad-snouted caiman (Caiman latirostris).

Endocrine disrupting compounds (EDCs) are contaminants ubiquitously found in the environment, which pose a potential threat to aquatic and wetland ecosystems. Caiman latirostris, a crocodilian species that inhabits South American wetlands, is highly sensitive to EDC exposure. Previously, we reported that early postnatal exposure to EDCs such as Bisphenol A (BPA) and 17ß-Estradiol (E2) alters C. latirostris oviduct differentiation. The aim of this work was to elucidate the molecular mechanisms behind this alteration. To accomplish this, we established the ontogenic changes in histological features and the expression of Wnt-7a, Wnt-5a, ß-catenin, FoxA2, desmin, and alpha smooth muscle actin (α-SMA) in the oviduct of C. latirostris. Then, we evaluated the effects of BPA and E2 exposure on these histological features and protein expressions. Our results showed that during the postnatal differentiation of the oviduct the presence of histological features related to adenogenesis is associated with the levels of expression of FoxA2, ß-catenin, Wnt-5a and Wnt-7a. Early postnatal exposure to BPA and E2 decreased the presence of histological features related to adenogenesis and altered the levels of expression of FoxA2, ß-catenin, Wnt-5a and Wnt-7a, as well as the desmin/α-SMA ratio. These findings suggest that altered levels of Wnt-7a, Wnt-5a, ß-catenin and FoxA2 could play a role in the BPA and E2-induced alteration in oviduct differentiation in C. latirostris. Thus, impaired adenogenesis and, probably, impaired reproduction in wildlife naturally exposed to BPA and other estrogenic agonists cannot be completely ruled out.

[The German version of the Bath Body Perception Disturbance Scale (BBPDS-D) : Translation, cultural adaptation and linguistic validation on patients with complex regional pain syndrome]. / Die deutsche Version der Bath Body Perception Disturbance Scale (BBPDS-D) : Übersetzung, kulturelle Anpassung und linguistische Validierung an Patienten mit komplexem regionalem Schmerzsyndrom.

BACKGROUND: Besides the classical clinical manifestations, body perception disturbances are common among patients with complex regional pain syndrome (CRPS). The Bath Body Perception Disturbance Scale (BBPDS) represents a useful tool to assess these changes in CRPS patients; however, to date no validated German version is available. OBJECTIVE: The aim of this study was to translate the BBPDS into German, to perform a cross-cultural adaptation and linguistic validation in patients with acute (symptoms <3 months) and stable (symptoms ≥3 months) CRPS. MATERIAL AND METHODS: The original English version of the BBPDS was translated into German according to published guidelines (translation and back translation) and tested on 56 patients (mean age 50.9 ± 13.1 years) with acute (n = 28) or stable (n = 28) CRPS. RESULTS: The relative reliability, intraclass correlation and test-retest reliability were excellent overall and in the groups with acute and stable CRPS. The smallest detectable change was at 10 points. In the test-retest 48 points lay within the 95% confidence interval and visual inspection showed no tendency towards heteroscedasticity. Spearman's ρ­coefficient values showed no correlation between the total score of the BBPDS-D with the numerical rating scale (NRS, ρ = -0.19) and the EuroQol-5 D (ρ = 0.16). There were no significant differences between patients with acute and stable CRPS (p = 0.412). There were also no floor or ceiling effects. CONCLUSION: This German translation and cross-cultural adaptation of the original English version of the BBPDS is a valid instrument to assess body perception disturbances in German speaking CRPS patients. Future research should further assess the impact of body perception disturbance on treatment outcome and prognosis.

[Diseases and overuse injuries of the lower extremities in long distance runners]. / Erkrankungen und Überlastungsschäden an der unteren Extremität bei Langstreckenläufern.

Running is one of the most popular sports worldwide, with running events attracting hundreds of thousands of runners of all age groups. Running is an effective way to improve health but is also associated with a high risk of injuries. Up to 50% of regular runners report having more than one injury each year. Some injuries are caused by an accident but most are caused by overuse. The most frequent diagnoses are patellofemoral pain syndrome, tibial stress syndrome (shin splint), Achilles tendinopathy, iliotibial band friction syndrome (runner's knee), plantar fasciitis and stress fractures of the metatarsals and tibia. The knee is the most frequently injured joint in runners at all distances. Hamstring injuries are typically acute resulting in a sudden, sharp pain in the posterior thigh. Hip injuries are less common but it can be more difficult to make the correct diagnosis and treatment is more complex. Clinicians confronted by runners with shin pain must distinguish between stress fractures of the tibia, tibial stress syndrome (shin splints) and chronic exertional compartment syndrome. Foot and ankle injuries are the most common injuries reported by long distance and marathon runners. Excess body weight and the number of kilometers run per week are high risk factors for injuries. The roles of other factors, such as shoes, stretching and biomechanics are less clear. A detailed anamnesis and physical examination are important for the correct diagnosis or the necessity for further diagnostic imaging and subsequent therapy.

An interatomic potential for saturated hydrocarbons based on the modified embedded-atom method.

In this work, we developed an interatomic potential for saturated hydrocarbons using the modified embedded-atom method (MEAM), a reactive semi-empirical many-body potential based on density functional theory and pair potentials. We parameterized the potential by fitting to a large experimental and first-principles (FP) database consisting of (1) bond distances, bond angles, and atomization energies at 0 K of a homologous series of alkanes and their select isomers from methane to n-octane, (2) the potential energy curves of H2, CH, and C2 diatomics, (3) the potential energy curves of hydrogen, methane, ethane, and propane dimers, i.e., (H2)2, (CH4)2, (C2H6)2, and (C3H8)2, respectively, and (4) pressure-volume-temperature (PVT) data of a dense high-pressure methane system with the density of 0.5534 g cc(-1). We compared the atomization energies and geometries of a range of linear alkanes, cycloalkanes, and free radicals calculated from the MEAM potential to those calculated by other commonly used reactive potentials for hydrocarbons, i.e., second-generation reactive empirical bond order (REBO) and reactive force field (ReaxFF). MEAM reproduced the experimental and/or FP data with accuracy comparable to or better than REBO or ReaxFF. The experimental PVT data for a relatively large series of methane, ethane, propane, and butane systems with different densities were predicted reasonably well by the MEAM potential. Although the MEAM formalism has been applied to atomic systems with predominantly metallic bonding in the past, the current work demonstrates the promising extension of the MEAM potential to covalently bonded molecular systems, specifically saturated hydrocarbons and saturated hydrocarbon-based polymers. The MEAM potential has already been parameterized for a large number of metallic unary, binary, ternary, carbide, nitride, and hydride systems, and extending it to saturated hydrocarbons provides a reliable and transferable potential for atomistic/molecular studies of complex material phenomena involving hydrocarbon-metal or polymer-metal interfaces, polymer-metal nanocomposites, fracture and failure in hydrocarbon-based polymers, etc. The latter is especially true since MEAM is a reactive potential that allows for dynamic bond formation and bond breaking during simulation. Our results show that MEAM predicts the energetics of two major chemical reactions for saturated hydrocarbons, i.e., breaking a C-C and a C-H bond, reasonably well. However, the current parameterization does not accurately reproduce the energetics and structures of unsaturated hydrocarbons and, therefore, should not be applied to such systems.

Finite element analysis of occupant head injuries: parametric effects of the side curtain airbag deployment interaction with a dummy head in a side impact crash.

In this study, we investigated and assessed the dependence of dummy head injury mitigation on the side curtain airbag and occupant distance under a side impact of a Dodge Neon. Full-scale finite element vehicle simulations of a Dodge Neon with a side curtain airbag were performed to simulate the side impact. Owing to the wide range of parameters, an optimal matrix of finite element calculations was generated using the design method of experiments (DOE); the DOE method was performed to independently screen the finite element results and yield the desired parametric influences as outputs. Also, analysis of variance (ANOVA) techniques were used to analyze the finite element results data. The results clearly show that the influence of moving deformable barrier (MDB) strike velocity was the strongest influence parameter on both cases for the head injury criteria (HIC36) and the peak head acceleration, followed by the initial airbag inlet temperature. Interestingly, the initial airbag inlet temperature was only a ~30% smaller influence than the MDB velocity; also, the trigger time was a ~54% smaller influence than the MDB velocity when considering the peak head accelerations. Considering the wide range in MDB velocities used in this study, results of the study present an opportunity for design optimization using the different parameters to help mitigate occupant injury. As such, the initial airbag inlet temperature, the trigger time, and the airbag pressure should be incorporated into vehicular design process when optimizing for the head injury criteria.

Investigating occupant safety through simulating the interaction between side curtain airbag deployment and an out-of-position occupant.

The objective of this research is to elucidate the effect of side curtain airbag deployment on occupant injuries and safety when the occupant is either in-position or out-of-position (OOP). We used side impact vehicle collision simulations with a 1996 Dodge Neon model, which was further modified to include a side curtain airbag, a seatbelt, and a 50th percentile Hybrid III dummy. The airbag used in the study was inflated using both the uniform pressure (UP) and smooth particle hydrodynamics (SPH) methods. In-position and OOP simulations were performed to assess and establish guidelines for airbag aggressivity thresholds and occupant position versus risk of injury. Three different OOP scenarios (OOP1, OOP2, OOP3) were initially setup following the work of Lund (2003), then modified such that the dummy's head was closer to the airbag, increasing the chance of injury caused by the airbag. The resultant head acceleration as a function of time for in-position and OOP simulations shows that both UP and SPH methods produce similar peak accelerations in cases where the airbag is fully inflated prior to impact. In all cases, the head peak accelerations and the head injury criteria for simulations with an airbag were significantly lower when compared with the no airbag case, which would typically indicate that the use of an airbag results in improved occupant protection during side impact. However, in the case of OOP2 and OOP3, the neck flexion forces actually increase significantly when compared with the no airbag case. This finding indicates that the HIC and neck flexion forces criterion are in conflict and that there may be a tradeoff in terms of occupant injury/safety with a side curtain airbag that is strongly correlated to the occupant position. Consequently, this study shows that safety devices result in a significant effect on occupant injury/safety when the occupant is in OOP conditions. Moreover, in some cases, simulation results show that the side curtain airbag may not make the occupant safer. This study requires further investigation of the vehicle-specific airbag and its interaction with an occupant in various OOP conditions.

Delayed reconstruction after eyelid tumor excision.

BACKGROUND: The aim of this study is to report the feasibility of one to two weeks delayed reconstruction after eyelid tumor excision. PATIENTS AND METHODS: A retrospective case-series study was designed. Fourteen consecutive outpatients referred to a tertiary referral eye center for eyelid tumor management were enrolled. The intervention imvolved eyelid tumor excision (with four millimeters surrounding clinically tumor-free tissue), compressive patching of the excised area until reconstruction (with or without a therapeutic contact lens), extensive histological work-up to assess histological tumor clearance, and reconstruction one week after excision (in a couple of patients after two weeks when further excision was necessary to achieve tumor clearance). Excision and closure were performed by a single external trained oculoplastic surgeon (IOH) with a day per week (Fridays) operating slot. As outcome we assessed whether such an approach has led before, during, or after eyelid reconstruction to unusual major adverse events (follow-up time: 18 - 36 months). RESULTS: Delaying up to one week, in some cases even two weeks, reconstruction after eyelid tumor excision was not associated with any unusual major adverse events before, during, or after surgery. CONCLUSIONS: When necessary, after eyelid tumor excision, it is possible to delay for one week or even for two weeks reconstruction, apparently without experiencing major unusual adverse events.

Mucosal excision instead of fashioning nasolacrimal mucosae flaps during external dacryocystorhinostomy: a pilot study.

BACKGROUND: To report results of a simplified external dacryocytorhinostomy procedure in which nasal and lacrimal sac mucosal flaps are simply removed instead of being sutured together. DESIGN: Retrospective non-comparative case-series study. PARTICIPANTS: Fourteen consecutive outpatients patients undergoing external dacryocytorhinostomy. INTERVENTION: Modified and simplified transcutaneous external dacryocytorhinostomy where basically the lacrimal sac and the nasal mucosae are widely excised in front of DCR's osteotomy instead of being used to fashion nasolacrimal flaps. OUTCOME: Assessment of dacryocytorhinostomy anatomical patency by syringing and patient's self-perception of epiphora symptoms improvement about twelve weeks and one year after surgery, as well as patient's report of ocular air-reflux during Valsalva maneuver a year after surgery. RESULTS: Syringing showed anatomic patency in 93 % and 92 % of patients twelve weeks (mean ± SD: 12 weeks ± 6 weeks) and one year (15 months ± 3 months) after surgery, respectively. One year after surgery, 62 % of patients reported ocular air-reflux. Twelve weeks and one year after surgery, mean symptom improvement was 82 % ± 17 % and 79 % ± 29 %, respectively. Furthermore, 79 % and 85 % of patients reported a postoperative improvement of their symptoms greater or equal to 80 % after twelve weeks and one year, respectively. CONCLUSIONS: Removing lacrimal sac and nasal mucosae in front of the osteotomy did not appear to have a major negative impact on the outcome of the external dacryocytorhinostomy. The findings of this pilot study need to be confirmed by a larger prospective trial.

Measurement of gamma' precipitates in a nickel-based superalloy using energy-filtered transmission electron microscopy coupled with automated segmenting techniques.

Precipitates of the ordered L1(2) gamma' phase (dispersed in the face-centered cubic or FCC gamma matrix) were imaged in Rene 88 DT, a commercial multicomponent Ni-based superalloy, using energy-filtered transmission electron microscopy (EFTEM). Imaging was performed using the Cr, Co, Ni, Ti and Al elemental L-absorption edges in the energy loss spectrum. Manual and automated segmentation procedures were utilized for identification of precipitate boundaries and measurement of precipitate sizes. The automated region growing technique for precipitate identification in images was determined to measure accurately precipitate diameters. In addition, the region growing technique provided a repeatable method for optimizing segmentation techniques for varying EFTEM conditions.

Towards clinically available closed-loop systems for mechanical ventilation in the intensive care unit.

OBJECTIVE: To provide an overview of the state-of-the-art of closed-loop systems in the field of mechanical ventilation. METHODS: This survey is reviewing the literature and proposes an overview of existing closed-loop systems, in different areas of mechanical ventilation. It discusses the key points that guided their development and addresses specific issues such as their performance and penetration at the bedside. RESULTS: Much research has been undertaken in the hope of improving patient-ventilator interaction and shortening the weaning process. This led to the development of new modes of ventilation and expert weaning systems that are starting to achieve a wider clinical audience. CONCLUSION: Intensive care unit personnel are facing increasing work load during care for patients with severe, multi-system illness, using sophisticated equipment that generate high information flows requiring quick processing. Mechanical ventilation is a good example of a process that requires skillful and timely management of multiple parameters that could be delegated to closed-loop systems. Availability of commercial offerings, validated by randomized controlled trials in a well-defined set of clinical situations, is starting to fulfill the promise of intelligent systems skillfully assisting caregivers at the bedside.

Fatal fulminant myocarditis caused by disseminated mucormycosis.

Acute fulminant myocarditis is a critical clinical condition with sudden onset of severe congestive heart failure followed by severe haemodynamic deterioration. Instituting early left ventricular support may improve outcome and result in better long term survival. The case of an immunocompromised patient who developed acute fulminant myocarditis in the setting of disseminated mucormycosis is presented.

Severe IgA-mediated auto-immune haemolytic anaemia in a 48-yr-old woman.

Auto-immune haemolytic anaemia (AIHA) is characterised by haemolysis associated with the presence of the immunoglobulins IgG, IgM or IgA, and/or components of the complement system on the red cell membrane. The immunoglobulins react as auto-antibodies against the red cell antigens of the patient. IgG antibodies and the complement component C3d can be detected by the direct antiglobulin test (DAT); however, IgM and particularly IgA antibodies may not necessarily be detected by the broad-spectrum anti-human-globulin serum. We present the case of a 48-yr-old woman with severe AIHA. The initial polyspecific direct antiglobulin test (DAT), using a broad-spectrum antiserum, was negative. Testing with monospecific antisera led to the diagnosis of AIHA due to warm-acting auto-antibodies solely of the IgA class, which is a very rare finding. As therapy with steroids alone did not lead to a lasting remission, splenectomy was performed 10 months after initial diagnosis. There has been no relapse of AIHA since, even after steroid medication was withdrawn and even though the monospecific IgA-DAT has remained positive. This case demonstrates the importance of performing a monospecific antiglobulin test if there is a strong suspicion of AIHA in apparently "Coombs-negative" haemolytic anaemia. In AIHA caused by solely IgA antibodies, the polyspecific direct antiglobulin test may be negative or only weakly positive because of a limited content of anti-IgA antibodies in the polyspecific anti-human-globulin serum. First-line treatment of warm-type AIHA is the administration of high-dose glucocorticosteroids; splenectomy is indicated in steroid-refractory patients.

Zooming in on the hydrophobic ridge of H-2D(b): implications for the conformational variability of bound peptides.

Class I major histocompatibility complex (MHC) molecules, which display intracellularly processed peptides on the cell surface for scanning by T-cell receptors (TCRs), are extraordinarily polymorphic. MHC polymorphism is believed to result from natural selection, since individuals heterozygous at the corresponding loci can cope with a larger number of pathogens. Here, we present the crystal structures of the murine MHC molecule H-2D(b) in complex with the peptides gp276 and np396 from the lymphocytic choriomeningitis virus (LCMV), solved at 2.18 A and 2.20 A resolution, respectively. The most prominent feature of H-2D(b) is a hydrophobic ridge that cuts across its antigen-binding site, which is conserved in the L(d)-like family of class I MHC molecules. The comparison with previously solved crystal structures of peptide/H-2D(b) complexes shows that the hydrophobic ridge focuses the conformational variability of the bound peptides in a "hot-spot", which could allow optimal TCR interaction and discrimination. This finding suggests a functional reason for the conservation of this structural element.

Use of handheld computers as bedside information providers.

Access to clinical reference information at the point-of-care is a goal that is difficult to achieve by lack of really portable reference material. Handheld computers have matured to the point where they are powerful enough to be used as clients of a distributed knowledge system serving reference information and decision-aid applications in a highly portable form factor. We describe a pilot project launched at the Geneva University Hospital studying the use of handhelds and associated clinical applications in two internal medicine clinics. Results garnered by this study will help answer the many questions raised by the use of handhelds in medical practice, in term of cost, benefits, risk and change in workflow.

Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex.

Caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the downstream executioner caspase-3 is a physiological target. Caspases are cysteine proteases that are specific for substrates with an aspartic acid residue at the P(1) position and have an optimal recognition motif that incorporates four amino acid residues N-terminal to the cleavage site. Caspase-8 has been classified as a group III caspase member because it shows a preference for a small hydrophobic residue at the P(4) substrate position. We report the X-ray crystallographic structure of caspase-8 in complex with benzyloxycarbonyl-Asp-Glu-Val-Asp-aldehyde (Z-DEVD), a specific group II caspase inhibitor. The structure shows that the inhibitor interacts favourably with the enzyme in subsite S(4). Kinetic data reveal that Z-DEVD (K(i) 2 nM) is an almost equally potent inhibitor of caspase-8 as the specific group III inhibitor Boc-IETD-aldehyde (K(i) 1 nM). In view of this finding, the original classification of caspases into three specificity groups needs to be modified, at least for caspase-8, which tolerates small hydrophobic residues as well as the acidic residue Asp in subsite S(4). We propose that the subsite S(3) must be considered as an important specificity-determining factor.

The effects of in vitro hemodilution with gelatin, hydroxyethyl starch, and lactated Ringer's solution on markers of coagulation: an analysis using SONOCLOT.

UNLABELLED: Blood-saving strategies have recently been established to avoid allogeneic transfusion during surgery or after trauma. This includes an expanding use of crystalloids and colloids. These solutions interfere with coagulation systems, but quantitative measurements are still lacking. The SONOCLOT (Sienco Company, Morrison, CO) analysis (SCT), a viscoelastic test, measures clot formation and includes information on the cellular, as well as the plasmatic coagulation, system. To quantify hemodilutional effects on in vitro coagulation, we studied gelatin (G), hydroxyethyl starch 6% (HES; molecular weight 450,000), and lactated Ringer's solution (RL) in 33% and 66% dilutions measuring routines laboratory and SCT variables. Hemodilution with RL tended to increase in vitro coagulability. Among the tested colloids, G had the least impact on markers of coagulation. G33% did not differ significantly from the undiluted control group. HES had the largest impact on markers of coagulation compared with G and RL. In conclusion, SCT provides a fast and easy to perform bedside test to quantify in vitro hemodilution. IMPLICATIONS: The effects of progressive hemodilution on coagulation are difficult to measure. SONOCLOT analyses provide an easy to perform test with fast information on cellular and plasmatic coagulation properties. Among colloids, hydroxyethyl starch has the largest impact on markers of coagulation compared with gelatin or lactated Ringer's solution.

[Simultaneous measurement of blood concentrations of O2 and CO with a Van Slyke apparatus]. / Mesures simultanées des concentrations sanguines en O2 et en CO à l'appareil de Van Slyke.

imultaneous analysis of a blood sample for its O2 and CO contents (Co2 and Cco) with the original manometric technique of Van Slyke entails a directional error on Co2 and Cco when blood contains CO. This important drawback is due to the fact that Na2S2O4 employed for the O2 absorption also reduces methemoglobin into hemoglobin which then reabsorbs a variable amount of the extracted CO. This amount is equal to the directional error and results in an overestimation of Co2 and in an underestimation of Cco. In order to analyze and possibly correct for this error, we have measured it by gas chromatography by determining Cco on blood samples with and without O2 absorption by Na2S2O4. The error has been found to be a function of both blood CO and Hb contents. An equation and a nomogram are presented allowing correction of the results obtained by the Van Slyke method. So corrected the results are equally precise in presence and in absence of CO (+/- 0.1 volume %) which makes simultaneous Co2 and Cco measurements with this classical and unexpensive method quite acceptable.

Cardiovascular effects of vasopressin infused into the vertebral circulation of conscious dogs.

1. Seven conscious dogs received arginine-vasopressin infusions (100 and 1000 fmol min--1 kg--1) through catheters implanted in the left vertebral artery or the inferior vena cava while arterial pressure, cardiac output (electromagnetic flowmeter) and heart rate were measured. 2. Despite similar increases in plasma vasopressin concentrations, intravertebral administration induced a lesser increase in mean arterial pressure and a greater decrease in heart rate than the same infusion given intravenously. 3. These results suggest that vasopressin has an effect on structures of the central nervous system involved in cardiovascular control, possibly by affecting the baroreceptor reflex.