Myofibrillar Characteristics of Porcine Stress Syndrome

Porcine Stress Syndrome (PSS) is a genetic trait causing considerable economic loss to the swine industry through stress related death and the poor quality meat known as pale, soft, exudative (PSE) pork . A scanning and transmission electron microscopic examination of muscle biopsies from stress susceptible pigs revealed contracture bands , wide separation of myofibers and focal distortion and dissolution of myofibril s . The changes affecting myofibrillar characteristics and intra and intercellular accumulation of material suspected to be myoplasmic fluid in biopsies of halothane reactors suqqest that the myopathic alterations presaging the carcass deterioration into pale, soft , exudative pork are integrants of this syndrome and that the PSE trait may not be a postmortem change triggered by the environmental factors just prior to or during slaughter

The Psychometric Properties of a Self-Administered, Open-Source Module for Valuing Metastatic Epidural Spinal Cord Compression Utilities.

INTRODUCTION: Web surveys are often used for utility valuation. Typically, custom utility valuation tools that have not undergone psychometric evaluation are used. OBJECTIVES: This study aimed to determine the psychometric properties of a metastatic epidural spinal cord compression (MESCC) module run on a customizable open-source, internet-based, self-directed utility valuation platform (Self-directed Online Assessment of Preferences [SOAP]). METHODS: Individuals accompanying patients to the emergency department waiting room in Ottawa, Canada, were recruited. Participants made SOAP MESCC health state valuations in the waiting room and 48 h later at home. Validity, agreement reliability, and responsiveness were measured by logical consistency of responses, smallest detectable change, the interclass correlation coefficient, and Guyatt\u27s responsiveness index, respectively. RESULTS: Of 285 participants who completed utility valuations, only 113 (39.6%) completed the re-test. Of these 113 participants, 92 (81.4%) provided valid responses on the first test and 75 (66.4%) provided valid responses on the test and re-test. Agreement for all groups of health states was adequate, since their smallest detectable change was less than the minimal clinically important difference. The mean interclass correlation coefficients for all health states were \u3e 0.8, indicating at least substantial reliability. Guyatt\u27s responsiveness indices all exceeded 0.80, indicating a high level of responsiveness. CONCLUSIONS: To our knowledge, this is the first validated open-source, web-based, self-directed utility valuation module. We have demonstrated the SOAP MESCC module is valid, reproducible, and responsive for obtaining ex ante utilities. Considering the successful psychometric validation of the SOAP MESCC module, other investigators can consider developing modules for other diseases where direct utility valuation is needed

Spontaneous nano-emulsification: Process optimization and modeling for the prediction of the nanoemulsion’s size and polydispersity

The aim of the present study was to optimize the size and polydispersity of a lipid nanoemulsion as a function of the oil (Labrafac® WL1349), surfactant (Kolliphor® HS 15) and cosurfactant (Span® 80) phase composition and temperature. The nanoemulsions were prepared using a low-energy self-emulsification method. The Z-average diameter and the polydispersity index (PDI) were modeled with mixture experiments. Nanoemulsions from 20 nm to 120 nm with PDI < 0.2 were obtained at the three different tested temperatures (30 °C, 50 °C and 90 °C). The nanoemulsion size was able to be controlled with the oil, surfactant and cosurfactant concentrations. Interestingly, the smallest PDIs were obtained at 30 °C, and the cosurfactant concentration was able to be adjusted to optimize the formulation and to obtain nanoemulsions in the 20–120 nm range with a PDI smaller than 0.14. These nanoemulsions have shown a good stability at 4 °C in storage conditions and at 37 °C in diluted conditions

A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label-mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof-of-principle penetration experiments in human skin ex vivo

Meiotic kinetochores fragment into multiple lobes upon cohesin loss in aging eggs.

Chromosome segregation errors during female meiosis are a leading cause of pregnancy loss and human infertility. The segregation of chromosomes is driven by interactions between spindle microtubules and kinetochores. Kinetochores in mammalian oocytes are subjected to special challenges: they need to withstand microtubule pulling forces over multiple hours and are built on centromeric chromatin that in humans is decades old. In meiosis I, sister kinetochores are paired and oriented toward the same spindle pole. It is well established that they progressively separate from each other with advancing female age. However, whether aging also affects the internal architecture of centromeres and kinetochores is currently unclear. Here, we used super-resolution microscopy to study meiotic centromere and kinetochore organization in metaphase-II-arrested eggs from three mammalian species, including humans. We found that centromeric chromatin decompacts with advancing maternal age. Kinetochores built on decompacted centromeres frequently lost their integrity and fragmented into multiple lobes. Fragmentation extended across inner and outer kinetochore regions and affected over 30% of metaphase-II-arrested (MII) kinetochores in aged women and mice, making the lobular architecture a prominent feature of the female meiotic kinetochore. We demonstrate that a partial cohesin loss, as is known to occur in oocytes with advancing maternal age, is sufficient to trigger centromere decompaction and kinetochore fragmentation. Microtubule pulling forces further enhanced the fragmentation and shaped the arrangement of kinetochore lobes. Fragmented kinetochores were frequently abnormally attached to spindle microtubules, suggesting that kinetochore fragmentation could contribute to the maternal age effect in mammalian eggs

Core-multishell nanocarriers: transport and release of dexamethasone probed by soft x-ray spectromicroscopy

Label-free detection of core-multishell (CMS) nanocarriers and the anti-inflammatory drug dexamethasone is reported. Selective excitation by tunable soft X-rays in the O 1s-regime is used for probing either the CMS nanocarrier or the drug. Furthermore, the drug loading efficiency into CMS nanocarriers is determined by X-ray spectroscopy. The drug-loaded nanocarriers were topically applied to human skin explants providing insights into the penetration and drug release processes. It is shown that the core-multishell nanocarriers remain in the stratum corneum when applied for 100 min to 1000 min. Dexamethasone, if applied topically to human ex vivo skin explants using different formulations, shows a vehicle-dependent penetration behavior. Highest local drug concentrations are found in the stratum corneum as well as in the viable epidermis. If the drug is loaded to core-multishell nanocarriers, the concentration of the free drug is low in the stratum corneum and is enhanced in the viable epidermis as compared to other drug formulations. The present results provide insights into the penetration of drug nanocarriers as well as the mechanisms of controlled drug release from CMS nanocarriers in human skin. They are also compared to related work using dye-labeled nanocarriers and dyes that were used as model drugs

Chemical-induced contact allergy: from mechanistic understanding to risk prevention

Chemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8\u2009+\u2009T cell-mediated immune disease, resulting in erythema and eczema. Chemical allergy is of considerable importance to the toxicologist, who has the responsibility of identifying and characterizing the allergenic potential of chemicals, and estimating the risk they pose to human health. This review aimed at exploring the phenomena of chemical-induced contact allergy starting from a mechanistic understanding, immunoregulatory mechanisms, passing through the potency of contract allergen until the hazard identification, pointing out the in vitro models for assessing contact allergen-induced cell activation and the risk prevention