Infrared Thermography and Ultrasonography to Indirectly Monitor the Influence of Liner Type and Overmilking on Teat Tissue Recovery

Eight Danish Holstein cows were milked with a 1-mm thick specially designed soft liner on their right rear teat and a standard liner mounted under extra high tension on their left rear teat. Four of the animals were overmilked for 5 min. Rear teats were subjected to ultrasound examination on the first day and to infrared thermography on the second day. Teats were submersed in ethanol 20 min post-milking on the second day. Ultrasonography measurements showed that teat canal length increased by 30–41% during milking. Twenty minutes after milking, teats milked with modified standard liners still had elongated teat canals while teats milked with the soft liner were normalized. Overmilking tended to increase teat wall thickness. Approximately 80% of variability in teat canal length, from before teat preparation to after milking, could be explained by changes during teat preparation. Thermography indicated a general drop in teat temperature during teat preparation. Teat temperature increased during milking and continued to increase until the ethanol challenge induced a significant drop. Temperatures approached pre-challenge rather than pre-milking temperatures within 10 minutes after challenge. Teat temperatures were dependent on type of liner. Mid-teat temperatures post-challenge relative to pre-teat preparation were dependent on overmilking. Thermography and ultrasound were considered useful methods to indirectly and non invasively evaluate teat tissue integrity

Tumor-associated macrophages in gliomas—basic insights and treatment opportunities

Glioma refers to a group of primary brain tumors which includes glioblastoma (GBM), astrocytoma and oligodendroglioma as major entities. Among these, GBM is the most frequent and most malignant one. The highly infiltrative nature of gliomas, and their intrinsic intra- and intertumoral heterogeneity, pose challenges towards developing effective treatments. The glioma microenvironment, in addition, is also thought to play a critical role during tumor development and treatment course. Unlike most other solid tumors, the glioma microenvironment is dominated by macrophages and microglia—collectively known as tumor-associated macrophages (TAMs). TAMs, like their homeostatic counterparts, are plastic in nature and can polarize to either pro-inflammatory or immunosuppressive states. Many lines of evidence suggest that immunosuppressive TAMs dominate the glioma microenvironment, which fosters tumor development, contributes to tumor aggressiveness and recurrence and, very importantly, impedes the therapeutic effect of various treatment regimens. However, through the development of new therapeutic strategies, TAMs can potentially be shifted towards a proinflammatory state which is of great therapeutic interest. In this review, we will discuss various aspects of TAMs in the context of glioma. The focus will be on the basic biology of TAMs in the central nervous system (CNS), potential biomarkers, critical evaluation of model systems for studying TAMs and finally, special attention will be given to the potential targeted therapeutic options that involve the TAM compartment in gliomas.publishedVersio

Quantitative vitreous fluorophotometry applying a mathematical model of the

A slit-lamp fluorophotometric method is presented that permits calculation of a blood-retinal barrier permeability to fluorescein (P) and a diffusion coefficient for fluorescein in the vitreous body (D). The calculations are performed by relating the time course of the free-not protein bound-fluorescein concentration in the bloodstream with the fluorescein concentration profile in the vitreous body. The combination is performed automatically on a computer by applying a simplified mathematical model of the eye. P refers to the area of the barrier of the model eye. In a group of six normal persons, the mean P was (1.1 ± 0.4) X 10~7 cm/sec (mean ± SD), while in six diabetic patients with background retinopathy and macular edema the mean P was (7.1 ± 3.8) X 10~7 cm/sec. The mean I) was (7.4 ± 3.4) X 10~6 cm 2 /sec in the normal group and (9.6 ± 2.0) X 1O~6 cm 2 /sec in diabetic patients, corresponding as a first approximation to free diffusion in water. Model calculations show that knowing the fluorescein concentration in the bloodstream is considerably significant for the calculation of the permeability, contributing factors up to 50%. For the low-permeation situation, subtraction of the preinjection scan contributes a factor of 50% for both permeability and diffusion coefficient. The exact placement in the vitreous body of the concentration profile, by applying a formalism that transforms slit-lamp movement to intraocular distance, contributes a factor of 20% on the diffusion coefficient. The permeability obtained with the model can be calculated as the ratio between area of vitreous and plasma fluorescein concentration curves within 20%. Active transport of fluorescein across the blood-retinal barrier in the direction of vitreous to blood does not seem to be significant within the first 2 hr after fluorescein injection. Invest Ophthalmol Vis Sci 26: [698][699][700][701][702][703][704][705][706][707][708][709][710] 1985 During the last 8 years, vitreous fluorophotometry has been used to quantitate the permeability properties of the blood-retinal barrier to fluorescein. The method, originally introduced by Cunha-Vaz and co-workers, 12 has been based upon intravenous (IV) injection of a standard dose of fluorescein, which usually after 60 min was followed by a slit-lamp photometric determination of the fluorescein concentration in the vitreous body. The magnitude of the concentration in the posterior part of the vitreous body has been used as a measurement of the barrier permeability. However, as it has been pointed out, it is important to incorporate the fluorescein concentration in the plasma in the calculation of the perme- ability of the barrier 3 " 13 and to include more than the concentration of fluorescein in a single point of the vitreous body in the calculations. An analysis of the fluorescein concentration profile in the vitreous body can, furthermore, provide qualitative information of the diffusion properties in the vitreous body. 14 Quantitative evaluation of this factor has previously been reported for the anterior vitreous 3 and recently for the posterior part of the vitreous body, based upon first principles. 13 The present article presents a more complete method for the calculation of a blood-retinal barrier permeability to fluorescein and a diffusion coefficient for fluorescein in the posterior part of the vitreous body. The method is based upon simultaneous determinations of the fluorescein concentration in plasma and in vitreous body. These data are combined on a computer by applying a simplified mathematical model of the eye to give a fluorescein permeability of the barrier and a diffusion coefficient for fluorescein in the vitreous body. The method, which is based on a series of studies of 165 human examinations, is presented here in detail. The individual clinical studies will be presented elsewhere in separate articles. The mathematical model has been described previously, Materials and Methods Fluorophotometric Equipment Slit lamp: The slit lamp is a Rodenstock 2001 mounted with oculars (700-10 Gamma Scientific; San Diego, CA) which in their focal point contain a 450 jum fiber optic probe picking up light from the slitlamp focal plane as described by Cunha-Vaz 1 and by Krogsaa et al. 17 In the focal plane, the slit is 1 mm high and 0.1 mm wide. The angle between slit and symmetry axis of the biomicroscope is 11.4° and the angle between symmetry axis and ocular is 5.6°. The light source of the slit lamp is a 450 W zenon arc lamp connected with the slit lamp by a fiber optic cable. This cable is interrupted by a light chopper (Rofin 7500; Rofin, England), which chops the light with a frequency of 432 Hz. The intensity of the blue light in the slit is 5 mW/cm 2 , as determined by a fluxmeter (Hewlett Packard type 8330 A). The filters used are a blue (SWP 495) and yellow (LWP 515) interference filter (Optical Laboratory; Lyngby, Denmark), with transmission characteristics as shown in Amplification and registration equipment: The light from the optic probe in the ocular is passed to a photomultiplier (initially a Gamma Scientific Model D-46 but now a PR-1400 RF, Products for Research Inc.; Danvers, MA) operated at room conditions. The photomultiplier is directly connected with an amplifier triggered from the chopper (Lock-in, Model 128 A, Princeton Applied Research; Princeton, NJ). This system increases the sensitivity of the equipment by a factor of seven. The lock-in amplifier is connected to the Y-axis of a X-Y recorder (Philips PM 8041; Eindhoben, Netherlands). The sagittal movement of the slit lamp is transduced to the X-axis of the recorder by a precision potentiometer. A mechanical device connected to the potentiometer secures that the movement of the slit lamp occurs in the sagittal plane. A foot switch allows an indication to be made on the X-axis in all desired positions of the slit-lamp focal plane and thereby also the ocular fiber optic probe in relation to the ocular structures, which are in focus when the focal plane is moved from retina to cornea. The X-Y recorder is coupled in parallel to a microcomputer Sensitivity and spatial resolution of the equipment: The sensitivity of the equipment defined as the concentration required to yield a signal twice as high as the background noise was 2.5 X 10~9 g/ml. A crosssection of the volume of measurement-the optical diamond 1819 -is constituted by a parellelogram measuring (0.48 X 2.16) mm with a diagonal of 2.64 mm. The spatial resolution was tested in a double compartment cuvette Although the optical diamond, as calculated from an analysis of the optics of the slit-lamp equipment, has the same geometry in these in vitro experiments The Fluorophotometric Examination Fluorescein administration and analysis in blood: Flourescein (14 mg/kg body weight) was injected in an antecubital vein over a 60-sec period. From a cannula in an antecubital vein in the other arm, blood samples were obtained before, and 5, 15, 30, 60, and 120 min after injection. After centrifugation plasma was analyzed for total as well as free (not protein-bound) fluorescein concentration, the latter by ultrafiltration, as described in detail elsewhere. 6 ' 7 Briefly, the analysis is performed in the following way: Blood is collected in heparinized test tubes. After centrifugation plasma is ultrafiltrated using the Amicon MPS-1 system (Amicon Corporation; Danvers, MA). Initially, Millipore Ultra Free disposable filters were used, giving the same results as the Amicon filters. The total fluorescein concentration is determined after sufficient dilution of plasma. As a control of the method and an estimation of the free fluorescein concentration in the bolus during its first passage through the ocular circulation, fluorescein is added to plasma samples obtained before injection of fluorescein; these samples were analyzed in the same way as the other plasma samples. The concentration of total fluorescein in these test samples is 5 X 10~6 g/ml, 5 X 10~5 g/ml, and 3 X 10" 4 g/ml, the latter corresponding to the assumed concentration in the bolus. The free fraction constitutes approximately 15% for all the concentration ranges. The bolus concentration: The concentration of fluorescein in the ocular arterial, capillary, and venous system during the fluorescein injection is unknown (the bolus concentration), but it can be estimated according to the following reasoning. The fluorescein solution (1 X 10" 1 g/ml) is injected over a 1-min period. It is assumed that the cardiac output is 5 1/min; hematocrit, 43%; and recirculation and extraction in pulmonary circulation is neglected. A person of 70 kg will receive 9.8 ml fluorescein over the 1-min period, and the total plasma fluorescein concentration in the bolus will accordingly be 10"' X 9.8 5000 X 0.57 = 3.4 X 10~4g/ml. Assuming an unbound fluorescein concentration of 15% at this concentration, 7 the concentration in the bolus during the 1 min of injection will be 5 X 10" 5 g/ml. Fluorophotometry: The present article is based on experience obtained over a 3-year period in which 165 examinations were performed. Two typical examinations, one with low leakage (normal person) and one with high leakage (diabetic patient), are shown in the article. The examination is performed after the eye is anaesthetized with oxybuprocaine (0.4%) and the pupil dilated with metaoxidrin (10%) and 0.5% tropicamide. A Goldmann contact lens (Haag-Streit AG; Liebefeld, Switzerland) with specifications given elsewhere 17 is used. An axial fluores- 701 cence scan is made before injection of fluorescein and 30, 60, and 120 min after injection. The scan is obtained in the following way: First the macula is focused. The slit lamp and its focal plane is then moved manually toward the examiner through the vitreous body, the lens, and the anterior chamber with a speed of less than 2 mm/sec, which secures that the amplification system, which operates with a time constant of 0.3 sec, is able to follow the slitlamp movement. A time constant of 0.1 sec gave the same results. However, the noise was then too high for the low-permeation situation, and 0.3 sec was chosen for all measurements. A feedback system signals if the speed is higher than 2 mm/sec. Informed consent was obtained from the persons examined after the nature of the procedures had been explained fully. Calculation of a Blood-Retinal Barrier Permeability and a Diffusion Coefficient in the Vitreous Body The calculation of permeability (P) and diffusion coefficient (D) is performed by linking the concentration course of free fluorescein in the plasma with the concentration profile in the vitreous body. This linkage is performed by the application of a simplified model of the eye. The model that will be described in more detail below is coupled on a large computer (see Larsen et al 10 ). However, before transmission of data to the large computer, three procedures are performed on the small computer (SPC/1), where data are collected on line: (1) the X-axis is transformed to real intraocular distances; (2) the fluorescence signal obtained before injection is subtracted from the signal obtained after injection; and (3) the amount of data is reduced. Transformation of the X-axis to intraocular distance: The movement of the slit lamp is, as mentioned, transduced to the X-axis by a potentiometer. By knowing the amplification of recorder and potentiometer, a movement on the X-axis can be transformed to movement of the slit lamp. The slit lamp movement, however, cannot be transformed directly to intraocular distances. Due to the refraction of light in the compound optical system, the movement of the slit-lamp focal plane is different from the movement of the slit lamp itself. 151718 -20 With the knowledge of the ratio between the two movements, the X-axis movement of the pen on the recorder can be transformed to intraocular distances according to the equation: where X e is intraocular distance; X r , distance on recorder; F, the ratio (movement of focal plane in the eye/movement of slit lamp); and M, the amplification of recorder and potentiometer, which in the present set up is 1:12.1. As shown by Krogsaa et al. Correction for preinjection value: The autofluorescence signal, which is obtained before injection of fluorescein, is converted to intraocular fluorescence signal by the same procedure as described above. The ordinate value of corresponding intraocular positions of the preinjection curve is subtracted automatically from the actual concentration profile obtained. MOVEMENT OF SLIT LAMP (0.5 mm step) 17 F is calculated for every 0.5-mm movement of the slit lamp. It appears that F is different for the three segments of the eye (anterior chamber, lens, and vitreous body) and varies within the individual compartments. marker point 2 to the center of the eye are transmitted to the computer and used for further analysis. Together with the transmission of the concentration profile, the time course of the free fluorescein concentration in the plasma is also transmitted to the central computer. The Simplified Model of the Eye and its Mathematical Formalism The simplified model: In order to calculate a permeability of the blood-retinal barrier and a diffusion coefficient in the vitreous body a simplified model of the eye was developed, as schematically shown in The mathematical formalism: The formulation of the mathematical formalism and the solution of the equations which describe the combination of the model parameters are given in detail elsewhere. where c m (rj, t) is the measured value at r = r is and c is the corresponding value given by equation (2). Equatio

Sustainable bioethanol production combining biorefinery principles using combined raw materials from wheat undersown with clover-grass

To obtain the best possible net energy balance of the bioethanol production the biomass raw materials used need to be produced with limited use of non-renewable fossil fuels. Intercropping strategies are known to maximize growth and productivity by including more than one species in the crop stand, very often with legumes as one of the components. In the present study clover-grass is undersown in a traditional wheat crop. Thereby, it is possible to increase input of symbiotic fixation of atmospheric nitrogen into the cropping systems and reduce the need for fertilizer applications. Furthermore, when using such wheat and clover-grass mixtures as raw material, addition of urea and other fermentation nutrients produced from fossil fuels can be reduced in the whole ethanol manufacturing chain. Using second generation ethanol technology mixtures of relative proportions of wheat straw and clover-grass (15:85, 50:50, and 85:15) were pretreated by wet oxidation. The results showed that supplementing wheat straw with clover-grass had a positive effect on the ethanol yield in simultaneous saccharification and fermentation experiments, and the effect was more pronounced in inhibitory substrates. The highest ethanol yield (80% of theoretical) was obtained in the experiment with high fraction (85%) of clover-grass. In order to improve the sugar recovery of clover-grass, it should be separated into a green juice (containing free sugars, fructan, amino acids, vitamins and soluble minerals) for direct fermentation and a fibre pulp for pretreatment together with wheat straw. Based on the obtained results a decentralized biorefinery concept for production of biofuel is suggested emphasizing sustainability, localness, and recycling principle

Nurse-Initiated Treatment Reduces Costs for Acute Asthma in a Pediatric Emergency Department

Standardized emergency department (ED) pathways can improve care delivery to children with acute asthma, though their impact on hospitalization and costs is unclear. An Acute Asthma Care Pathway (AACP) that facilitates nurse initiation of treatment was implemented at a tertiary care pediatric ED using standard quality improvement methodology. The impact of implementation was assessed using process control methodology and multivariable time series analyses between pre- and post-implementation periods. Provision of a steroid within 30 minutes and 60 minutes of arrival increased by 21 and 22 percentage points respectively, IV magnesium sulfate administration increased by 30 percentage points, the proportion hospitalized decreased from 44.8% to 32.2%, and mean direct costs per patient decreased from $2,663 to$2,303 (13.5%). In multivariable analysis, these improvements remained significant. Implementation of the AACP improved timeliness of treatment, hospitalization, and direct costs of children receiving ED treatment for acute asthma

In-Vitro Validated Methods for Encoding Digital Data in Deoxyribonucleic Acid (DNA)

Deoxyribonucleic acid (DNA) is emerging as an alternative archival memory technology. Recent advancements in DNA synthesis and sequencing have both increased the capacity and decreased the cost of storing information in de novo synthesized DNA pools. In this survey, we review methods for translating digital data to and/or from DNA molecules. An emphasis is placed on methods which have been validated by storing and retrieving real-world data via in-vitro experiments

Investigation into impact of train speed for behaviour of ballasted railway track foundations

Traffic congestion of highways in many countries around the world has led railways to become the most popular means of public transportation, which increased the demand for faster and heavier trains. High-speed trains and heavy train loads are normally accompanied with strong vibrations in the track-ground system, which increases the risk of train derailment and track damages. Therefore, to allow for safer and reliable operation of high-speed trains, an investigation into the behavior of ballasted railway track foundations subjected to train moving loads at various speeds is a subject of prime importance in design of railway tracks. In the current study, sophisticated three dimensional (3D) finite elements (FE) numerical modelling was developed to investigate the impact of train speed on the dynamic response of track-ground system. In addition, some factors of the track-ground system affecting the critical speed including the modulus and thickness of track subgrade and ballast materials, and amplitude of train loading were investigated. The results were analyzed and presented, and their practical implications were discussed

Bis(guanidinium) chloranilate

The asymmetric unit of the title co-crystal, 2CH6N3 +·C6Cl2O4 2−, contains one half of a chloranilate anion and one guanidinium cation, which are connected by strong N—H⋯O hydrogen bonds into a two-dimensional network

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Horses in Denmark Are a Reservoir of Diverse Clones of Methicillin-Resistant and -Susceptible Staphylococcus aureus

Denmark is a country with high prevalence of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 in pigs. Even though pig farming is regarded as the main source of human infection or colonization with MRSA CC398, 10–15% of the human cases appear not to be linked to pigs. Following the recent reports of MRSA CC398 in horses in other European countries and the lack of knowledge on S. aureus carriage in this animal species, we carried out a study to investigate whether horses constitute a reservoir of MRSA CC398 in Denmark, and to gain knowledge on the frequency and genetic diversity of S. aureus in horses, including both methicillin-resistant and -susceptible S. aureus (MSSA). Nasal swabs were collected from 401 horses originating from 74 farms, either at their farms or prior to admission to veterinary clinics. Following culture on selective media, species identification by MALDI-TOF MS and MRSA confirmation by standard PCR-based methods, S. aureus and MRSA were detected in 54 (13%) and 17 (4%) horses originating from 30 (40%) and 7 (9%) farms, respectively. Based on spa typing, MSSA differed genetically from MRSA isolates. The spa type prevalent among MSSA isolates was t127 (CC1), which was detected in 12 horses from 11 farms and represents the most common S. aureus clone isolated from human bacteremia cases in Denmark. Among the 17 MRSA carriers, 10 horses from three farms carried CC398 t011 harboring the immune evasion cluster (IEC), four horses from two farms carried IEC-negative CC398 t034, and three horses from two farms carried a mecC-positive MRSA lineage previously associated with wildlife and domestic ruminants (CC130 t528). Based on whole-genome phylogenetic analysis of the 14 MRSA CC398, t011 isolates belonged to the recently identified horse-adapted clone in Europe and were closely related to human t011 isolates from three Danish equine veterinarians, whereas t034 isolates belonged to pig-adapted clones. Our study confirms that horses carry an equine-specific clone of MRSA CC398 that can be transmitted to veterinary personnel, and reveals that these animals are exposed to MRSA and MSSA clones that are likely to originate from livestock and humans, respectively