Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.

This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60 mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4 weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4 weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.

Electronic health records: new opportunities for clinical research.

Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.

[Mini-Mental State Examination in geriatrics : An evaluation of diagnostic quality]. / Mini-Mental-Status-Test im stationären geriatrischen Bereich.

BACKGROUND: Several studies have identified moderate reliability and validity for the Mini-Mental State Examination (MMSE). Some researchers showed the superiority of other dementia screening tests over the MMSE considering the test quality criteria. The aim of this study was the evaluation of MMSE, especially in the area of geriatrics. PATIENTS AND METHODS: MMSE and DemTect were carried out with 154 geriatric patients: 71 persons without cognitive impairment and 83 persons without delirium showed cognitive impairments as revealed by the DemTect. In addition, we also applied the Clock-Drawing-Test (CDT), Reisberg-Scale, Geriatric Depression-Scale (GDS, 15-item version) and the Confusion-Assessment-Method (CAM). RESULTS: According to the multitrait-multimethod approach, MMSE's convergent and divergent validity is similar to that of the DemTect. Both tests correlate only moderately with Spearman (r = 0.609) and revealed similar results for dementia in 57.1 % of the patients. MMSE showed low reliability and moderate reliability (Cronbach's α = 0.82) when ten items with low discriminatory power were excluded from the total test score. Difficulty of all items is only moderate (p = 0.86) and only eight items of the MMSE showed good test difficulty. CONCLUSION: All in all, DemTect and MMSE are not interchangeable. The MMSE estimates the average cognitive impairment of patients as considerably less pronounced than the DemTect. MMSE is, thus, not an instrument that would be recommended for the identification of mild cognitive impairment. In this case, tests with higher reliability and validity should be used.

Roots and associated fungi drive long-term carbon sequestration in boreal forest.

Boreal forest soils function as a terrestrial net sink in the global carbon cycle. The prevailing dogma has focused on aboveground plant litter as a principal source of soil organic matter. Using (14)C bomb-carbon modeling, we show that 50 to 70% of stored carbon in a chronosequence of boreal forested islands derives from roots and root-associated microorganisms. Fungal biomarkers indicate impaired degradation and preservation of fungal residues in late successional forests. Furthermore, 454 pyrosequencing of molecular barcodes, in conjunction with stable isotope analyses, highlights root-associated fungi as important regulators of ecosystem carbon dynamics. Our results suggest an alternative mechanism for the accumulation of organic matter in boreal forests during succession in the long-term absence of disturbance.

Domestic animal models for biomedical research.

Experimental animals in biomedical research provide insights into disease mechanisms and models for determining the efficacy and safety of new therapies and for discovery of corresponding biomarkers. Although mouse and rat models are most widely used, observations in these species cannot always be faithfully extrapolated to human patients. Thus, a number of domestic species are additionally used in specific disease areas. This review summarizes the most important applications of domestic animal models and emphasizes the new possibilities genetic tailoring of disease models, specifically in pigs, provides.

Diagnosis and management of a fracture of the lateral trochlear ridge of the talus in a dog.

An eight-month-old, 31.2 kg, entire male Golden Retriever was presented for evaluation because it had a four-week history of right hindlimb lameness and audible popping occurring in association with movement of the right hindlimb. Mild right hindlimb lameness was noted upon gait analysis. Moderate to severe effusion and pain on extension were appreciated on palpation of the right tarsus. Dorsoplantar and lateral radiographs of the right tarsus revealed significant soft tissue swelling over the lateral aspect of the tarsus and widening of the joint space over the lateral trochlear ridge of the talus. A fracture of the lateral ridge was appreciated upon evaluation of the flexed dorsoplantar view. Un-enhanced computed tomography of the right tarsus confirmed fracture of the talus; one large and two small bone fragments were noted adjacent to the lateral aspect of the lateral trochlear ridge and medial to the fibula. The fracture was surgically repaired via a lateral approach; a fibular osteotomy was performed. The fragment was manually reduced and secured with a 1.5 mm cortical screw placed in lag fashion. The fibular osteotomy site was reduced and fixed with two 1.6 mm Kirshner wires and a tension band composed of 0.9 mm cerclage wire. The patient made a complete clinical recovery, however, the union was fibrous and evidence of mild osteo- arthritis was noted on postoperative radiographs.

Osteomyelitis-related sequestrum formation in association with the combination tibial plateau levelling osteotomy and cranial closing wedge osteotomy procedure.

A twenty-eight-month old female spayed American Bulldog was presented for evaluation of a chronic draining tract and intermittent left hindlimb lameness twenty-eight weeks after a combination tibial plateau levelling osteotomy and cranial closing wedge osteotomy (TLPO/CCWO) had been performed. The patient had developed an infection of the surgical site three weeks postoperatively. Drainage persisted despite implant removal 10 weeks postoperatively and several weeks of culture and sensitivity-directed antibiotic therapy. Twenty-eight weeks postoperatively, a sequestrum was identified on radiographs. Surgical removal of the sequestrum resulted in resolution of the drainage. While osteomyelitis is a known complication of TPLO surgery, this case represents the first described case of osteomyelitis-related sequestrum formation in association with the combined TPLO/CCWO procedure.

Numerical dosimetry ELF: accuracy of the method, variability of models and parameters, and the implication for quantifying guidelines.

In situ electric fields and current densities are investigated by numerical simulations for exposure to ELF electric and magnetic fields. Computations are based on the finite-difference time-domain method (FDTD). The computational uncertainty is determined by comparison of analytical and numerical results and amounts to a worst-case expanded uncertainty (95% confidence interval) of +/-9.89 dB for both dosimetric quantities (E, J). Detailed investigations based on the Visible Human body model with a resolution of 2 mm show a strong influence of the tissue boundaries on the simulation results, which is caused by the numerical method. For the tissue specific in situ electric field and current density changes in excess of 10 dB are observed when comparing the results with and without evaluation of the dosimetric quantities at tissue boundaries. Moderate sensitivities with respect to tissue boundaries are observed only for low conductivity tissues when evaluating the in situ electric field whereas this behavior is observed for high conductivity tissues when evaluating the current density. For exposure to a 50 Hz magnetic field corresponding to the ICNIRP reference level, the simulated current density for central nervous system (CNS) tissue is in compliance with the ICNIRP guidelines. Exposure to a 50 Hz electric field may exceed the ICNIRP basic restriction for CNS tissue at least in a worst-case scenario (grounded human body, vertical electric field, tissue boundaries included for the evaluation of the current density). The in situ electric field is the more stable dosimetric quantity with respect to changes of the tissue conductivity of the Visible Human body model. The maximum conductivity sensitivity coefficient amounts to +122% for the current density whereas the maximum sensitivity coefficient for the in situ electric field is -20%. For electric field exposure the in situ electric field remains comparable (-6% to -4%), the averaged current density change ranges from -57% to -16% for the tissues under investigation. Magnetic field exposure of a scaled model of a five year old child leads to a decrease of the dosimetric quantities (J: -74% to -45%, E: -42% to -23%) compared to the Visible Human results.

[Extrathoracal pulmonary sequestration in the differential diagnosis of paravertebral tumors in the neonate]. / Extrathorakale Lungensequestration als Differenzialdiagnose paravertebraler Raumforderungen beim Neugeborenen.

BACKGROUND: Paravertebral masses of the fetus are often detected during routine prenatal ultrasonography. The most common differential diagnoses of these tumors are neuroblastoma, adrenal hemorrhage, schwannoma and germ cell tumors. CASE REPORT: We report on a mature male newborn, who was diagnosed antenatally at 23 + 3 weeks of gestation with a tumor in the left paravertebral region. After birth the child was transferred to a neonatal unit. Tumor markers like urinary catecholamines were within normal limits, neuron-specific enolase was slightly elevated. MRI as well as ultrasonography confirmed a 3.2 x 2.2 x 1.6 cm large smoothed edged tumor in the left paravertebral region at the level of T10-T12. An open biopsy was performed, and the tumor which was located below the diaphragma was subtotally resected. Histopathology showed an extralobar pulmonary sequestration. Surgery as well as postoperative course was uneventful. CONCLUSIONS: Extralobar pulmonary sequestrations represent rare congenital anomalies, which are usually asymptomatic. Clear differentiation between tumor and pulmonary sequestration is seldom possible despite high resolution imaging studies. Hence, a biopsy procedure should be done for diagnosis of paravertebral masses.

Results of plate fixation of type 5 olecranon fractures in 20 horses.

REASONS FOR PERFORMING STUDY: Previous olecranon fracture reports contain a small proportion of type 5 fractures, mostly treated with conservative therapy. OBJECTIVES: To evaluate the clinical details and outcome of type 5 olecranon fractures in a large group of horses treated by tension band plate fixation and to compare results with other treatment methods. METHODS: Medical records of 97 cases, including 32 (33%) classified as type 5, were reviewed. Subject details, history, radiographic findings, treatment and follow-up results (2-146 months post operatively) were recorded. RESULTS: Treatment included open reduction and internal fixation using a narrow or broad dynamic compression plate (n = 20), conservative therapy (n = 7) and euthanasia (n = 5). Long-term follow-up was available in 15 cases treated surgically, of which 2 were sound and in training, 11 sound and performing athletically and 2 unsound. Distal semilunar notch involvement, comminution or open status did not appear to affect prognosis. CONCLUSIONS: Internal plate fixation provides an excellent prognosis for an animal to be capable of athletic performance. POTENTIAL RELEVANCE: Describing tension band plate fixation and results offers a method of fracture repair that should improve treatment and prognosis for type 5 olecranon fractures.

Meal size and starch content affect gastric emptying in horses.

REASONS FOR PERFORMING STUDY: Feeding practices have been associated with colic in horses. If meal size and composition have an effect on gastric emptying, this could be one of the mechanisms by which feeding practices are related to the occurrence of colic. OBJECTIVES: To evaluate the effect of meal size and starch content on solid phase gastric emptying. METHODS: Solid phase gastric emptying of 3 different radiolabelled meals, small low-starch (SmLS), small high-starch (SmHS) and large high-starch (LgHS) meals, was measured in 5 horses by scintigraphy using 99mTc-disofenin. Data were compared among meals using nonlinear mixed-effects models and paired t tests. RESULTS: On a percentage basis, SmHS emptied significantly faster than LgHS and SmLS emptied significantly faster than SmHS meals. However, when meals of unequal size were compared by emptying rate in g/min and Kcal/min, LgHS emptied significantly faster than SmHS. CONCLUSIONS: Meal size and composition affect gastric emptying. POTENTIAL RELEVANCE: Further work needs to be performed in order to substantiate the possibility of a relationship between digestive functions and occurrence of colic and gastric ulcers.

Results of plate fixation of type 1b olecranon fractures in 24 horses.

REASONS FOR PERFORMING STUDY: Previous olecranon fracture reports contain a small proportion of type 1b fractures, with only a few repaired by tension band plate fixation. OBJECTIVES: To evaluate subject details, history, clinical findings and outcome of type 1b olecranon fractures in a large group of horses treated by tension band plate fixation. METHODS: Medical records of 77 horses diagnosed with an olecranon fracture were reviewed. Twenty-four horses (31%) were classified as having type 1b olecranon fractures. Clinical details and follow-up results (4-128 months post operatively) were recorded. RESULTS: Treatment included open reduction and internal fixation using a narrow dynamic compression plate (n = 20), conservative therapy (n = 2) and euthanasia (n = 2). Long-term follow-up was available for 16 plated horses. Four were sound and in training and 9 were sound and performing athletically. Articular surface involvement, comminution, open status or removal of anconeal process fragments did not appear to affect prognosis or soundness. CONCLUSIONS: Internal plate fixation provides an excellent prognosis for an animal capable of athletic performance. POTENTIAL RELEVANCE: Describing tension band plate fixation and results offers a method of fracture repair that will improve the treatment and prognosis for type 1b olecranon fractures.

Validation of the 13C-octanoic acid breath test for measurement of equine gastric emptying rate of solids using radioscintigraphy.

REASONS FOR PERFORMING STUDY: Disordered gastric motility may be a significant factor in the pathogenesis of many equine conditions. Although tests for liquid phase emptying rate have been validated in the horse, there are no effective tests for solid phase emptying measurement that can be performed routinely in the field. OBJECTIVES: The objective of this study was the assessment of a novel stable isotope technique, the 13C-octane acid breath test (13C-OABT), for the measurement of gastric emptying of solid ingesta, by direct comparison with the optimum method of gastric scintigraphy. METHODS: To facilitate dual measurement of gastric emptying, a test meal was used containing baked egg yolk labelled with both 13C-octanoic acid and 99mtechnetium sulphur colloid. Simultaneous, serial lateral gastric scintigraphs and expiratory breath samples were obtained in 12 healthy horses after voluntary ingestion of the test meal. Analysis of breath 13CO2:12CO2 ratio was performed by continuous flow isotope ratio mass spectrometry. Power regression was used to determine the gastric emptying coefficient, the gastric half-emptying time (t 1/2) and duration of the lag phase (tlag). RESULTS: Significant correlations (P < 0.001) were found between the 2 techniques for measurement of both t 1/2 and tlag. In addition, scintigraphic left t 1/2 was correlated significantly to breath test gastric emptying coefficient (P < 0.001). CONCLUSIONS: It was concluded that the 13C-octanoic acid breath test is a reliable diagnostic procedure to measure gastric emptying rate of solids in the horse. POTENTIAL RELEVANCE: Being safe, noninvasive and easy to perform, this test has potential value as both sensitive diagnostic modality and humane research tool for motility studies.

Active medical implants and occupational safety--measurement and numerical calculation of interference voltage.

Low frequency electric and magnetic fields may interfere with implanted cardiac pacemakers causing a life-threatening malfunction of the device. In order to assess the safety of workers in the vicinity of industrial electrical devices the interference voltage at the input port of a pacemaker is an important measure. In order to investigate the coupling of fields emanating from electrical devices a numerical method for the calculation of interference voltages is presented and applied to the investigation of homogeneous electric and magnetic fields in the frequency range from 50 Hz to 1 MHz. Implantation of the pacemaker in the right pectoral, left pectoral and abdominal area using a realistic model of the human body as well as different grounding conditions are considered. The numerical method is successfully validated by measurements and shows good agreement with results in the literature.

Quantitative detection of atropine-delayed gastric emptying in the horse by the 13C-octanoic acid breath test.

The 13C-octanoic acid breath test has been correlated significantly to radioscintigraphy for measurement of gastric emptying indices in healthy horses. The objective of this study was to investigate the validity of the test for measurement of equine delayed gastric emptying, prior to its potential clinical application for this purpose. A model of atropine-induced gastroparesis was used. Gastric emptying rate was measured twice in 8 horses using concurrent radioscintigraphy and/or breath test after treatment i.v. with either atropine (0.035 mg/kg bwt) or saline in randomised order. Analysis of both data sets demonstrated that the atropine treatment had caused a significant delay in gastric emptying rate. Paired breath test data showed an atropine-induced delay in gastric half-emptying time (t 1/2), with no overlap in the 99% CI range (P < 0.001). Significant correlations were found between scintigraphy and 13C-octanoic acid breath test for calculation of both t 1/2 (P < 0.01) and lag phase duration (P < 0.05) in the atropine-delayed emptying results. The mean (s.d.) bias in breath test t 1/2 when compared with scintigraphy was 1.78 (0.58) h. The results demonstrated that the 13C-octanoic acid breath test was an effective diagnostic modality for the measurement of equine delayed gastric emptying. The technique offers advantages to existing methods for clinical investigation, as it is noninvasive, not radioactive, quantitative and requires minimal equipment or training to perform.

Renal hypoplasia and dysplasia in an American miniature foal.

Diagnostic imaging, including computed tomography, of a two-month-old foal with renal failure indicated that its right kidney was probably absent and that its left kidney was abnormal in shape. The foal was stabilised and released, but three days later its clinical signs recurred. Postmortem examination revealed renal hypoplasia and dysplasia, the first reported case of this condition in an American miniature horse.

Comparative genomic sequencing reveals a strikingly similar architecture of a conserved syntenic region on human chromosome 11p15.3 (including gene ST5) and mouse chromosome 7.

Comparative genomics is a superior way to identify phylogenetically conserved features like genes or regions involved in gene regulation. The comparison of extended orthologous chromosomal regions should also reveal other characteristic traits essential for chromosome or gene function. In the present study we have sequenced and compared a region of conserved synteny from human chromosome 11p15.3 and mouse chromosome 7. In human, this region is known to contain several genes involved in the development of various disorders like Beckwith-Wiedemann overgrowth syndrome and other tumor diseases. Furthermore, in the neighboring chromosome region 11p15.5 extensive imprinting of genes has been reported which might extend to region 11p15.3. The analysis of approximately 730 kb in human and 620 kb in mouse led to the identification of eleven genes. All putative genes found in the mouse DNA were also present in the same order and orientation in the human chromosome. However, in the human DNA one putative gene of unknown function could be identified which is not present in the orthologous position of the mouse chromosome. The sequence similarity between human and mouse is higher in transcribed and exon regions than in non-transcribed segments. Dot plot analysis, however, reveals a surprisingly well-conserved sequence similarity over the entire analyzed region. In particular, the positions of CpG islands, short regions of very high GC content in the 5' region of putative genes, are similar in human and mouse. With respect to base composition, two distinct segments of significantly different GC content exist as well in human as in the mouse. With a GC content of 45% the one segment would correspond to "isochore H1" and the other segment (39% GC in human, 40% GC in mouse) to "isochore L1/L2". The gene density (one gene per 66 kb) is slightly higher than the average calculated for the complete human genome (one gene per 90 kb). The comparison of the number and distribution of repetitive elements shows that the proportion of human DNA made up by interspersed repeats (43.8%) is significantly higher than in the corresponding mouse DNA (30.1%). This partly explains why the human DNA is longer between the landmark genes used to define the orthologous positions in human and mouse.

Evaluation of heart time-activity curves as a predictor of hepatic extraction of 99mTc-mebrofenin in dogs.

In this study, heart time-activity curve, created following intravenous injection of 99mTc-mebrofenin were used to quantify hepatic function in normal dogs and dogs with induced hepatic parenchymal cell damage. The results were compared to a direct measurement of hepatic extraction following mesenteric venous injection of 99mTc-mebrofenin. The heart time-activity curves were normalized and the area under the curve from 0-30 minutes and 0-60 minutes were determined. In addition, the half-time clearance rate of the heart time-activity curve was analyzed using a two-compartment model. Linear regression analysis was used to describe the relationship between the area under the normalized heart time-activity curve and hepatic extraction. There was good correlation between the area under the normalized heart time-activity curve and hepatic extraction. The best correlation was obtained from the 0-30 minute data (r2 = 0.92). A formula for calculating hepatic extraction was derived using linear regression analysis: Hepatic extraction = 1.092 - (0.0000308 x AUC0-30 minutes). There was good correlation between the half-time clearance rates from the heart time-activity curve and hepatic extraction. The best correlation was between the fast phase half-time clearance and hepatic extraction (r2 = 0.88). The area under a normalized heart time-activity curve can be used as a simple alternative to deconvolutional analysis for the determination of hepatic extraction as a measure of hepatic parenchymal cell function in the dog.

BAliBASE (Benchmark Alignment dataBASE): enhancements for repeats, transmembrane sequences and circular permutations.

BAliBASE is specifically designed to serve as an evaluation resource to address all the problems encountered when aligning complete sequences. The database contains high quality, manually constructed multiple sequence alignments together with detailed annotations. The alignments are all based on three-dimensional structural superpositions, with the exception of the transmembrane sequences. The first release provided sets of reference alignments dealing with the problems of high variability, unequal repartition and large N/C-terminal extensions and internal insertions. Here we describe version 2.0 of the database, which incorporates three new reference sets of alignments containing structural repeats, trans-membrane sequences and circular permutations to evaluate the accuracy of detection/prediction and alignment of these complex sequences. BAliBASE can be viewed at the web site http://www-igbmc.u-strasbg. fr/BioInfo/BAliBASE2/index.html or can be downloaded from ftp://ftp-igbmc.u-strasbg.fr/pub/BAliBASE2 /.