Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

When gas analysis assists with postmortem imaging to diagnose causes of death.

Postmortem imaging consists in the non-invasive examination of bodies using medical imaging techniques. However, gas volume quantification and the interpretation of the gas collection results from cadavers remain difficult. We used whole-body postmortem multi-detector computed tomography (MDCT) followed by a full autopsy or external examination to detect the gaseous volumes in bodies. Gases were sampled from cardiac cavities, and the sample compositions were analyzed by headspace gas chromatography-mass spectrometry/thermal conductivity detection (HS-GC-MS/TCD). Three categories were defined according to the presumed origin of the gas: alteration/putrefaction, high-magnitude vital gas embolism (e.g., from scuba diving accident) and gas embolism of lower magnitude (e.g., following a traumatic injury). Cadaveric alteration gas was diagnosed even if only one gas from among hydrogen, hydrogen sulfide or methane was detected. In alteration cases, the carbon dioxide/nitrogen ratio was often >0.2, except in the case of advanced alteration, when methane presence was the best indicator. In the gas embolism cases (vital or not), hydrogen, hydrogen sulfide and methane were absent. Moreover, with high-magnitude vital gas embolisms, carbon dioxide content was >20%, and the carbon dioxide/nitrogen ratio was >0.2. With gas embolisms of lower magnitude (gas presence consecutive to a traumatic injury), carbon dioxide content was <20% and the carbon dioxide/nitrogen ratio was often <0.2. We found that gas analysis provided useful assistance to the postmortem imaging diagnosis of causes of death. Based on the quantifications of gaseous cardiac samples, reliable indicators were determined to document causes of death. MDCT examination of the body must be performed as quickly as possible, as does gas sampling, to avoid generating any artifactual alteration gases. Because of cardiac gas composition analysis, it is possible to distinguish alteration gases and gas embolisms of different magnitudes.

Importance of anthropogenic climate impact, sampling error and urban development in sewer system design.

Urban drainage design relying on observed precipitation series neglects the uncertainties associated with current and indeed future climate variability. Urban drainage design is further affected by the large stochastic variability of precipitation extremes and sampling errors arising from the short observation periods of extreme precipitation. Stochastic downscaling addresses anthropogenic climate impact by allowing relevant precipitation characteristics to be derived from local observations and an ensemble of climate models. This multi-climate model approach seeks to reflect the uncertainties in the data due to structural errors of the climate models. An ensemble of outcomes from stochastic downscaling allows for addressing the sampling uncertainty. These uncertainties are clearly reflected in the precipitation-runoff predictions of three urban drainage systems. They were mostly due to the sampling uncertainty. The contribution of climate model uncertainty was found to be of minor importance. Under the applied greenhouse gas emission scenario (A1B) and within the period 2036-2065, the potential for urban flooding in our Swiss case study is slightly reduced on average compared to the reference period 1981-2010. Scenario planning was applied to consider urban development associated with future socio-economic factors affecting urban drainage. The impact of scenario uncertainty was to a large extent found to be case-specific, thus emphasizing the need for scenario planning in every individual case. The results represent a valuable basis for discussions of new drainage design standards aiming specifically to include considerations of uncertainty.

Postmortem magnetic resonance imaging of the heart ex situ: development of technical protocols.

Postmortem MRI (PMMR) examinations are seldom performed in legal medicine due to long examination times, unfamiliarity with the technique, and high costs. Furthermore, it is difficult to obtain access to an MRI device used for patients in clinical settings to image an entire human body. An alternative is available: ex situ organ examination. To our knowledge, there is no standardized protocol that includes ex situ organ preparation and scanning parameters for postmortem MRI. Thus, our objective was to develop a standard procedure for ex situ heart PMMR examinations. We also tested the oily contrast agent Angiofil® commonly used for PMCT angiography, for its applicability in MRI. We worked with a 3 Tesla MRI device and 32-channel head coils. Twelve porcine hearts were used to test different materials to find the best way to prepare and place organs in the device and to test scanning parameters. For coronary MR angiography, we tested different mixtures of Angiofil® and different injection materials. In a second step, 17 human hearts were examined to test the procedure and its applicability to human organs. We established two standardized protocols: one for preparation of the heart and another for scanning parameters based on experience in clinical practice. The established protocols enabled a standardized technical procedure with comparable radiological images, allowing for easy radiological reading. The performance of coronary MR angiography enabled detailed coronary assessment and revealed the utility of Angiofil® as a contrast agent for PMMR. Our simple, reproducible method for performing heart examinations ex situ yields high quality images and visualization of the coronary arteries.

An extraordinary case of an intracranial foreign body after a gunshot to the head.

Intermediate targets (IT) can modify the morphology of an entrance wound, the trajectory of the bullet, and contaminate the path with fragments or material from the target. The penetration into the body of big fragments or even of an entire IT is exceptional and only rarely reported in the literature. The interpretation of a gunshot wound after contact of the bullet with IT can sometimes be very tricky as the classical morphology can be missing. The presented case is a rare example of atypical entrance wound and path due to a surprising intermediate target of a gunshot fired against the head.

Sewer deterioration modeling with condition data lacking historical records.

Accurate predictions of future conditions of sewer systems are needed for efficient rehabilitation planning. For this purpose, a range of sewer deterioration models has been proposed which can be improved by calibration with observed sewer condition data. However, if datasets lack historical records, calibration requires a combination of deterioration and sewer rehabilitation models, as the current state of the sewer network reflects the combined effect of both processes. Otherwise, physical sewer lifespans are overestimated as pipes in poor condition that were rehabilitated are no longer represented in the dataset. We therefore propose the combination of a sewer deterioration model with a simple rehabilitation model which can be calibrated with datasets lacking historical information. We use Bayesian inference for parameter estimation due to the limited information content of the data and limited identifiability of the model parameters. A sensitivity analysis gives an insight into the model's robustness against the uncertainty of the prior. The analysis reveals that the model results are principally sensitive to the means of the priors of specific model parameters, which should therefore be elicited with care. The importance sampling technique applied for the sensitivity analysis permitted efficient implementation for regional sensitivity analysis with reasonable computational outlay. Application of the combined model with both simulated and real data shows that it effectively compensates for the bias induced by a lack of historical data. Thus, the novel approach makes it possible to calibrate sewer pipe deterioration models even when historical condition records are lacking. Since at least some prior knowledge of the model parameters is available, the strength of Bayesian inference is particularly evident in the case of small datasets.

Dynamic contrast-enhanced ultrasound (DCE-US) for easy and rapid evaluation of hepatocellular carcinoma compared to dynamic contrast-enhanced computed tomography (DCE-CT)--a pilot study.

PURPOSE: To check the feasibility of the easy quantification of tumor vascularization derived from dynamic contrast-enhanced ultrasound (DCE-US) in comparison to dynamic contrast-enhanced computed tomography (DCE-CT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 19 patients with cirrhosis and histologically proven HCC prospectively underwent CEUS (SonoVue) and CT (Imeron400). Following CEUS, the software ImageJ was used for the easy quantification of the echogenicity in HCC lesions and tumor-free liver parenchyma. For DCE-CT we used the software Hepacare and created arterial enhancement fraction color maps of the whole liver and HCC lesions. RESULTS: Unifocal/multifocal HCCs were detected in 12/7 (US) and 10/9 patients (CT) and biopsied nodules were defined as a reference lesion with a median of 40 mm (US) and 42 mm (CT). CEUS showed HCC-typical hyper-/hypoenhancement in the arterial/late phase in 16/19 reference lesions, while all reference lesions showed an HCC-typical vascular pattern in CT. With DCE-US, quantitative assessment could not be performed in 3/19 patients due to respiratory motion or insufficient image quality. 13/16 reference lesions showed an HCC-typical vascular pattern. Quantitative assessment was possible with DCE-CT in all patients and all reference nodules showed HCC-typical values of the arterial enhancement fraction. There was no statistical difference between CEUS, DCE-US and DCE-CT in the quantitative assessment of contrast enhancement. CONCLUSION: The quantitative evaluation of DCE-US was feasible in HCC without a statistical difference with respect to DCE-CT. Further studies with a larger study population including small nodules ≤ 2 cm are needed to assess whether this technique is helpful in routine ultrasound.

Impact of food intake, ultrasound transducer, breathing maneuvers and body position on acoustic radiation force impulse (ARFI) elastometry of the liver.

PURPOSE: Since acoustic radiation force impulse (ARFI) elastometry is an increasingly popular method for the assessment of hepatic fibrosis and cirrhosis, we investigated factors possibly influencing hepatic elastometric measurements. MATERIALS AND METHODS: 30 healthy volunteers (17 females, 13 males) were recruited. The shear wave velocity of the right liver lobe was determined in a fasting upright and supine position and after different breathing maneuvers with the convex array (4C1) and in a supine position with the linear (9L4) ultrasound transducer. In 18 volunteers, subsequent measurements were obtained in a fasting state and 30, 60, 90 and 120 min after ingestion of a standardized breakfast. A group of 8 patients (average age: 76 years) with right heart insufficiency was also evaluated. RESULTS: In the fasting state, the ARFI shear wave velocities measured in an upright position were significantly higher than those in supine position (p< 0.0001). The supine ARFI values were significantly higher with the linear transducer than with the convex transducer (p = 0.0034). The results in deep inspiration, deep expiration and during Valsalva maneuver showed no differences. The food intake-related ARFI elastometric measurements were significantly elevated at time points 30 min (p = 0.019) and 60 min (p = 0.036) postprandial. In right heart insufficiency, the ARFI values were elevated. CONCLUSION: Hepatic ARFI elastometry is a well evaluated method. A standardized examination should include measuring in a supine position with the convex transducer (4C1) without specific breathing maneuvers. Since ARFI elastometry values increase after food intake, measurements should be performed in the fasting state, or not earlier than 2 hours postprandially. Heart dysfunction may impair ARFI accuracy.

Development and validation of a postmortem radiological alteration index: the RA-Index.

This study aimed to derive an index quantifying the state of alteration of cadavers by quantifying the presence of gas in the body using postmortem multidetector computed tomography (MDCT) imaging, and to validate the index by defining its sensitivity and specificity. The RA (radiological alteration)-index was derived from postmortem MDCT data from 118 nontraumatically deceased people. To validate the index, 100 additional scanned bodies (50 % traumatically deceased) were retrospectively examined by two independent observers. Presence of gas at 82 sites was assessed by a radiologist, whereas a forensic pathologist only investigated the seven sites used for the RA-index. The RA-index was highly correlated to the overall presence of gas in all 82 sites (R(2) = 0.98 in the derivation set and 0.85 in the validation set). Semiquantitative evaluation of gas presence in each site showed moderate reliability (Cohen's kappa range, 0.41-0.78); nevertheless, the overall RA-index was very reliable (ICC(2,1) = 0.95; 95 % CI 0.92-0.96). Examiner using the RA-index detected heart cavities full of gas with a sensitivity of 100 % (95 % CI 51.7-100) and a specificity of 98.8 % (92.6-99.9). We conclude that determining the presence of gas at seven sites is a valid means to measure the distribution of gas due to cadaveric alteration in the entire body. The RA-index is rapid, easy-to-use, and reliable for nonexperienced users, and it is a valid method to suspect the normal presence of gas from cadaveric alteration. MDCT can be used to screen for gas embolism and to give indications for gas composition analysis (gas chromatography).

Analysis of the antibody responses induced by subcutaneous injection immunotherapy with birch and Fagales pollen extracts adsorbed onto aluminum hydroxide.

BACKGROUND: Allergen-specific subcutaneous immunotherapy (SCIT) is an antigen-specific therapy of IgE-mediated allergies. In the present study, we analyze the epitope specificities of antibody responses induced by SCIT with allergen extracts from pollen of trees belonging to the order Fagales (birch, alder, hazel) adsorbed onto aluminum hydroxide. METHODS: The IgE, IgG1-4 and IgA responses to defined recombinant allergens (birch pollen: Bet v 1; alder pollen: Aln g 1; hazel pollen: Cor a 1; apple: Mal d 1) as well as to Bet v 1-derived recombinant fragments and synthetic peptides were analyzed in sera from patients who had undergone SCIT for different periods of time. RESULTS: Long-term SCIT (>1 year; cumulative dose >1,000,000 SQ units) induced more pronounced IgG1, IgG2 and IgG4 responses to Bet v 1 and Bet v 1-related allergens according to the degree of sequence homology (Bet v 1>Aln g 1>Cor a 1>Mal d 1) than short-term SCIT (<1 year; cumulative dose <1,000,000 SQ units). In contrast to patients treated for <1 year, patients treated for >1 year mounted distinct IgG1, IgG2 and IgG4 responses against sequential Bet v 1 epitopes. No relevant allergen-specific IgA or IgG3 responses were induced by short- or long-term SCIT. Using a competitive ELISA assay, it could be shown that serum IgG from patients undergoing long-term SCIT inhibited IgE reactivity to Bet v 1 better than IgG from patients undergoing short-term SCIT. CONCLUSION: SCIT with allergen extracts adsorbed onto aluminum hydroxide induces IgG responses against new epitopes that block IgE binding and cross-react with structurally related allergens depending, among other factors, on duration of treatment and cumulative injected dose.

The allergen profile of beech and oak pollen.

BACKGROUND: Beech and oak pollen are potential allergen sources with a world-wide distribution. OBJECTIVE: We aimed to characterize the allergen profile of beech and oak pollen and to study cross-reactivities with birch and grass pollen allergens. METHODS: Sera from tree pollen-allergic patients with evidence for beech and oak pollen sensitization from Basel, Switzerland, (n=23) and sera from birch pollen-allergic patients from Vienna, Austria, (n=26) were compared in immunoblot experiments for IgE reactivity to birch (Betula pendula syn. verrucosa), beech (Fagus sylvatica) and oak (Quercus alba) pollen allergens. Subsequently, beech and oak pollen allergens were characterized by IgE inhibition experiments with purified recombinant and natural allergens and with allergen-specific antibody probes. Birch-, beech- and oak pollen-specific IgE levels were determined by ELISA. RESULTS: Beech and oak pollen contain allergens that cross-react with the birch pollen allergens Bet v 1, Bet v 2 and Bet v 4 and with the berberine bridge enzyme-like allergen Phl p 4 from timothy grass pollen. Sera from Swiss and Austrian patients exhibited similar IgE reactivity profiles to birch, beech and oak pollen extracts. IgE levels to beech and oak pollen allergens were lower than those to birch pollen allergens. CONCLUSION: IgE reactivity to beech pollen is mainly due to cross-reactivity with birch pollen allergens, and a Phl p 4-like molecule represented another predominant IgE-reactive structure in oak pollen. The characterization of beech and oak pollen allergens and their cross-reactivity is important for the diagnosis and treatment of beech and oak pollen allergy.

Characterization of highly porous polymeric materials with pore diameters larger than 100 nm by mercury porosimetry and X-ray scattering methods.

Highly porous polymeric materials with pore sizes ranging from 100 nm to 1 microm are a very challenging class of materials not only to prepare synthetically (due to the high capillary pressures generated upon solvent removal) but also to characterize structurally. Through the examples of three different types of porous compounds synthesized in our laboratory (i) high-density melamine-based "MF-hd" with monomodal pore diameters around 500-900 nm, (ii) low-density melamine-based "MF-ld" with bimodal pore size distribution and average diameters around 2.3 microm and 350 nm, (iii) highly porous polyurethane "PU" with monomodal pore sizes around 150 nm, we confirm the limitations of mercury porosimetry as a means to investigate the architecture of materials with very high porosity (>80 vol %) and low compressive strength. Instead, a combination of high-resolution scanning electron microscopy and small-angle and ultrasmall-angle X-ray scattering (SAXS and USAXS, respectively) studies of these three types of materials helps in determining both the network and the pore structures. This work elucidates the need and applicability of the SAXS/USAXS techniques in characterizing such porous materials. For instance, the polyurethane specimens can only be quantitatively characterized by scattering techniques, the results of which are corroborated by high-resolution scanning electron microscopy observations.

[Treatment results from inpatient psychosomatic rehabilitation of Turkish migrants: a prospective study]. / Behandlungsergebnisse stationärer psychosomatischer Rehabilitation bei türkischen Migranten: Eine prospektive Studie.

Psychosomatic rehabilitation and the concluding social-medical assessment constitute a particular challenge. The aim of this study was to examine whether inpatient psychosomatic rehabilitation in the context of an integrated treatment concept, conducted in Turkish and German, is effective in the rehabilitation of Turkish migrant laborers, and what concluding socio-medical assessment results from this treatment. 195 Turkish patients--44 male and 151 female--received inpatient psychosomatic treatment for approximately 40 days. Sociodemographic, psychiatric and social-medical data were recorded, as well as Symptom Checklist (SCL-90-R) testing upon admission and discharge. A predominant number of patients were laborers, with a low level of primary education, who were afflicted with psychosocial problems and dissatisfaction with their workplace and who first came into psychosomatic treatment many years following the onset of their illness. Many of them had a clearly defined desire to retire. At the end of their admission, a significant improvement in almost all the scales of the SCL-R-90 was ascertained on the one hand, but on the other, adequate socio-medical results were hardly observed. The symptoms' improvement would confirm that the combination of service offerings in Turkish and German proved themselves. A portion of the patients (approx. 40 %) were classified subsequent to treatment as capable of working for 6 hours or more. Nevertheless, approximately approx. 75 % still sought to retire. Timely psychosomatic treatment could counteract chronification of the illness and the establishment of a steadfast desire to enter retirement, and consequently represent an improvement in the prognosis. Likewise, consistent psychosomatic training of physicians, as well as systematic prophylactic measures with the migrant laborers, should be considered.

Intravenous mirtazapine is safe and effective in the treatment of depressed inpatients.

Mirtazapine is a third-generation antidepressant with a dual mode of action. The oral administration has been shown to be effective and safe in the treatment of depressed patients. In this multicenter naturalistic study, we assessed the safety, tolerability, and therapeutic efficacy of intravenously administered mirtazapine in 80 moderately to severely depressed inpatients during a treatment period of 14 days. We found a significant decrease of the Hamilton Depression Rating Scale total score compared to baseline. Side effects were mild and transient. Our data indicate that intravenous mirtazapine is an effective, safe and well-tolerated treatment for depressed inpatients.

[Treatment motivation and results of inpatient psychotherapy for women with depressive disorders: a prospective study]. / Behandlungsmotivation und Ergebnisse der stationären Psychotherapie bei Frauen mit depressiven Erkrankungen: eine prospektive Studie.

Whether the treatment results in inpatient psychotherapy are significantly influenced by the patient's motivation is a subject of discussion. The goal of this study was to assess whether the primary motivation for therapy in depressive women influences the results of psychotherapeutic treatment. In a prospective study, the monitored results from 64 female inpatients (32 who were highly motivated to enter therapy, and 32 who were minimally motivated) were compared to each other. The period of observation was six weeks. As instruments of assessment, the Fragebogen zur Therapiemotivation (FMP) (Questonnaire on Motivation for Entering Therapy) and the Beck Depression Inventory (BDI) were aministered upon admission; after the fourth and sixth weeks of therapy, the Veränderungsfragebogen des Erlebens und Verhaltens (VEV) (Questionnaire of Changes in Experience and Behavior) was administered as well. All patients who had applied for a pension were found in the group of less motivated patients and consolidated into a subgroup. The analysis was carried out according to the intent-to-treat principle. The variance analysis for the repeat measurements showed significant differences on all the FMP scales and on the BDI (all P< 0.001). The measurements with VEV likewise resulted in a significant difference (P< 0.01). The subgroup of "pension patients" showed significantly less change in all three of the above measurements. Patients with depressive symptomology who essentially are relatively highly motivated for therapy could profit significantly more from inpatient psychosomatic treatment than those who are less motivated. Establishing and developing motivation prior to inpatient hospitalization could possibly contribute to more efficient and cost-effective clinical treatment. Where legal proceedings pertaining to a pension are pending, relatively less motivated patients fare significantly worse not only in their motivational development for therapy, but also in their final treatment results. It should be noted, however, that the relatively small random sample, the restricted blinding, which was only partially possible, could have led to possible distortions.

A review on hyponatremia associated with SSRIs, reboxetine and venlafaxine.

Hyponatremia, defined as serum sodium below 135 mmol/l, is a potentially life-threatening condition and was shown to be more frequent in elderly and psychiatric patients. In the last years numerous case reports on SSRI- and venlafaxine-induced hyponatremia were published indicating a higher incidence than previously thought. Only few studies have been performed and the incidence reported varies widely from 4.6/1000 people to 25%. It is still unclear if any single SSRI shows a higher incidence of hyponatremia than the others. Some data suggest that venlafaxine may have a stronger association to hyponatremia than SSRIs. Risk factors include age, female sex, low body mass index, severe physical illness, history of former hyponatremia and co-medications known to induce hyponatremia, especially thiazide diuretics. Symptoms of hyponatremia are usually neuropsychiatric (e.g. restlessness, lethargy, cognitive impairment), and any worsening in psychiatric symptoms in patients with a corresponding risk-profile receiving SSRIs or venlafaxine should give cause to check serum electrolytes. Usually SSRI-induced hyponatremia occurs within approximately 30 days and is reported to improve after withdrawal of the drug. Further controlled studies to confirm the true incidence of hyponatremia due to SSRI or venlafaxine and to define predictors more precisely are needed.

In situ NMR and XRD studies of the growth mechanism of SBA-1.

In situ 17O, 14N and 29Si nuclear magnetic resonance (NMR) coupled with in situ energy dispersive X-ray diffraction (EDXRD) have been used to investigate the growth of the siliceous mesoporous material, SBA-1, synthesised under acidic conditions from a micellar solution of the surfactant hexadecyltriethylammonium bromide (HTEAB) and tetraethylorthosilicate (TEOS). For the last decade, the mechanism of growth of such materials has been thought to be driven by electrostatic interactions described as a co-assembly process between the silica species (I+) and the micelles (S(+)X(-)). However, this postulated model referred to as the "charge density matching model" has never been fully supported by experimental data for the acidic syntheses. We have carried out a detailed in situ study which challenges the so-called S(+)X(-)I(+) pathway and instead suggests that a salting-out effect coupled with a drastic change in the water activity are responsible for the composite I(1)3 (SBA-1 space group Pm3n) mesophase precipitation. Substantial reorganisation of the precipitated phase then results in the final structure.