Comparative proteomic profiling of the ovine and human PBMC inflammatory response.

Understanding the cellular and molecular mechanisms of inflammation requires robust animal models. Sheep are commonly used in immune-related studies, yet the validity of sheep as animal models for immune and inflammatory diseases remains to be established. This cross-species comparative study analyzed the in vitro inflammatory response of ovine (oPBMCs) and human PBMCs (hPBMCs) using mass spectrometry, profiling the proteome of the secretome and whole cell lysate. Of the entire cell lysate proteome (oPBMCs: 4217, hPBMCs: 4574 proteins) 47.8% and in the secretome proteome (oPBMCs: 1913, hPBMCs: 1375 proteins) 32.8% were orthologous between species, among them 32 orthologous CD antigens, indicating the presence of six immune cell subsets. Following inflammatory stimulation, 71 proteins in oPBMCs and 176 in hPBMCs showed differential abundance, with only 7 overlapping. Network and Gene Ontology analyses identified 16 shared inflammatory-related terms and 17 canonical pathways with similar activation/inhibition patterns in both species, demonstrating significant conservation in specific immune and inflammatory responses. However, ovine PMBCs also contained a unique WC1+γδ T-cell subset, not detected in hPBMCs. Furthermore, differences in the activation/inhibition trends of seven canonical pathways and the sets of DAPs between sheep and humans, emphasize the need to consider interspecies differences in translational studies and inflammation research.

A novel magnet-based scratch method for standardisation of wound-healing assays.

A novel magnetic scratch method achieves repeatability, reproducibility and geometric control greater than pipette scratch assays and closely approximating the precision of cell exclusion assays while inducing the cell injury inherently necessary for wound healing assays. The magnetic scratch is affordable, easily implemented and standardisable and thus may contribute toward better comparability of data generated in different studies and laboratories.

Diamondites: evidence for a distinct tectono-thermal diamond-forming event beneath the Kaapvaal craton.

The petrogenesis and relationship of diamondite to well-studied monocrystalline and fibrous diamonds are poorly understood yet would potentially reveal new aspects of how diamond-forming fluids are transported through the lithosphere and equilibrate with surrounding silicates. Of 22 silicate- and oxide-bearing diamondites investigated, most yielded garnet intergrowths (n = 15) with major element geochemistry (i.e. Ca-Cr) classifying these samples as low-Ca websteritic or eclogitic. The garnet REE patterns fit an equilibrium model suggesting the diamond-forming fluid shares an affinity with high-density fluids (HDF) observed in fibrous diamonds, specifically on the join between the saline-carbonate end-members. The δ13C values for the diamonds range from - 5.27 to - 22.48‰ (V-PDB) with δ18O values for websteritic garnets ranging from + 7.6 to + 5.9‰ (V-SMOW). The combined C-O stable isotope data support a model for a hydrothermally altered and organic carbon-bearing subducted crustal source(s) for the diamond- and garnet-forming media. The nitrogen aggregation states of the diamonds require that diamondite-formation event(s) pre-dates fibrous diamond-formation and post-dates most of the gem monocrystalline diamond-formation events at Orapa. The modelled fluid compositions responsible for the precipitation of diamondites match the fluid-poor and fluid-rich (fibrous) monocrystalline diamonds, where all grow from HDFs within the saline-silicic-carbonatitic ternary system. However, while the nature of the parental fluid(s) share a common lithophile element geochemical affinity, the origin(s) of the saline, silicic, and/or carbonatitic components of these HDFs do not always share a common origin. Therefore, it is wholly conceivable that the diamondites are evidence of a distinct and temporally unconstrained tectono-thermal diamond-forming event beneath the Kaapvaal craton.

Sulfide resorption during crustal ascent and degassing of oceanic plateau basalts.

Mantle plume-related magmas typically have higher chalcophile and siderophile element (CSE) contents than mid-ocean ridge basalts (MORB). These differences are often attributed to sulfide-under-saturation of plume-related melts. However, because of eruption-related degassing of sulfur (S) and the compositional, pressure, temperature and redox effects on S-solubility, understanding the magmatic behavior of S is challenging. Using CSE data for oceanic plateau basalts (OPB), which rarely degas S, we show that many OPB are sulfide-saturated. Differences in the timing of sulfide-saturation between individual OPB suites can be explained by pressure effects on sulfur solubility associated with ascent through over-thickened crust. Importantly, where S-degassing does occur, OPB have higher CSE contents than S-undegassed melts at similar stages of differentiation. This can be explained by resorption of earlier-formed sulfides, which might play an important role in enriching degassed melts in sulfide-compatible CSE and potentially contributes to anomalous enrichments of CSE in the crust.

Microfluidic nutrient gradient-based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model.

In this work, we describe a microfluidic three-dimensional (3D) chondrocyte culture mimicking in vivo articular chondrocyte morphology, cell distribution, metabolism, and gene expression. This has been accomplished by establishing a physiologic nutrient diffusion gradient across the simulated matrix, while geometric design constraints of the microchambers drive native-like cellular behavior. Primary equine chondrocytes remained viable for the extended culture time of 3 weeks and maintained the low metabolic activity and high Sox9, aggrecan, and Col2 expression typical of articular chondrocytes. Our microfluidic 3D chondrocyte microtissues were further exposed to inflammatory cytokines to establish an animal-free, in vitro osteoarthritis model. Results of our study indicate that our microtissue model emulates the basic characteristics of native cartilage and responds to biochemical injury, thus providing a new foundation for exploration of osteoarthritis pathophysiology in both human and veterinary patients.

The embryogenesis of the equine femorotibial joint: The equine interzone.

REASONS FOR PERFORMING STUDY: Articular cartilage regeneration is the focus and goal of considerable research effort. Since articular chondrocytes descend from a distinct cohort of progenitor cells located in embryonic nascent joints (interzones), establishing the timing of equine interzone formation is an essential first step towards understanding equine joint and articular cartilage development. OBJECTIVES: To establish the time frame during which the equine femorotibial interzone forms. STUDY DESIGN: Descriptive anatomical study. METHODS: Equine embryos were harvested at 37 (E37), 40, 42, 45, 50 and 65 days' gestation. The femorotibial interzone was examined using high-resolution episcopic microscopy of E37, E42, E45, E50 and E65. Additional histology and collagen-II-immunohistochemistry were performed on E42. RESULTS: At E37, the femorotibial interzone is first visible as a uniform layer, while at E42 the interzone is fully formed and consists of 3 morphologically distinct layers. The first evidence of cavitation was seen at E45. At E50, the cruciate ligaments were well formed and by E65, joint formation appeared complete. CONCLUSIONS: The embryogenesis of the equine femorotibial joint is similar to the developmental timeline of stage-matched human and murine embryos. Further studies looking at interzone formation on a cellular and molecular level may further our understanding of the intricate developmental patterns and pathways of articular cartilage development.

Magnetic resonance microscopy atlas of equine embryonic development.

REASONS FOR PERFORMING STUDY: Equine embryogenesis post implantation is not well studied, and only two-dimensional illustrations are available. A thorough appreciation of the complex three-dimensional relationship between tissues and organs and their development is, however, crucial for understanding physiological and pathological mechanisms. OBJECTIVES: The goals were 2-fold: 1) to establish a freely accessible online atlas as a reference tool for the scientific and pedagogic communities; and 2) to create a framework for integration of data with known spatiotemporal distribution, such as gene expression or cell lineage. STUDY DESIGN: Descriptive anatomical study. METHODS: Magnetic resonance microscopy was performed on embryos of 28, 32, 35, 37, 39, 40, 42, 45, 50 and 65 days gestation using a 9.4 T magnet. Equine embryos were staged according to the Carnegie system. Acquired images were optimised using histogram optimisation and processed for easy online access. RESULTS: Magnetic resonance microscopy protocols for imaging of equine embryos and fetuses were developed. The wider spread of signal intensity values achieved by histogram equalisation increased visual contrast considerably. Despite their longer gestation, equine conceptuses appeared to reach the various Carnegie staging benchmarks earlier than human embryos. CONCLUSIONS: The equine atlas is designed to serve as an online reference tool for research and teaching. POTENTIAL RELEVANCE: The equine atlas may serve as a foundation and scaffold for improved anatomical labelling, spatial and temporal data integration and further understanding of physiological and pathophysiological processes involved in development and disease.

Elasticity and breaking strength of synthetic suture materials incubated in various equine physiological and pathological solutions.

REASONS FOR PERFORMING STUDY: Selection of suture material in equine surgery is often based on costs or subjective factors, such as the surgeon's personal experience, rather than objective facts. The amount of objective data available on durability of suture materials with regard to specific equine physiological conditions is limited. OBJECTIVES: To evaluate the effect of various equine physiological and pathological fluids on the rate of degradation of a number of commonly used suture materials. STUDY DESIGN: In vitro material testing. METHODS: Suture materials were exposed in vitro to physiological fluid, followed by biomechanical analysis. Three absorbable suture materials, glycolide/lactide copolymer, polyglactin 910 and polydioxanone were incubated at 37°C for 7, 14 or 28 days in phosphate-buffered saline, equine serum, equine urine and equine peritoneal fluid from an animal with peritonitis. Five strands of each suture material type were tested to failure in a materials testing machine for each time point and each incubation medium. Yield strength, strain and Young's modulus were calculated, analysed and reported. RESULTS: For all suture types, the incubation time had a significant effect on yield strength, percentage elongation and Young's modulus in all culture media (P<0.0001). Suture type was also shown significantly to influence changes in each of yield strength, percentage elongation and Young's modulus in all culture media (P<0.0001). While the glycolide/lactide copolymer demonstrated the highest Day 0 yield strength, it showed the most rapid degradation in all culture media. For each of the 3 material characteristics tested, polydioxanone showed the least variation across the incubation period in each culture medium. CONCLUSIONS: The duration of incubation and the type of fluid have significant effects on the biomechanical properties of various suture materials. These findings are important for evidence-based selection of suture material in clinical cases.

Scapulohumeral osteochondrosis. A retrospective study of 32 horses.

OBJECTIVES: To review the outcome of equine shoulder osteochondrosis (OC) with surgical or conservative treatment. METHODS: Retrospective study of 32 horses, less than two years of age, with scapulohumeral joint (SHJ) OC. The lesion severity was graded based on measurements taken from lateromedial radiographs. Follow-up information was obtained from racing records or telephone conversations with owners. Successful outcome was defined as the ability of the horse to perform its intended use. RESULTS: Sixteen of 32 horses were affected bilaterally (48 joints). Eleven of 16 horses with bilateral OC underwent arthroscopic surgery; five had bilateral arthroscopy, six had unilateral arthroscopy of the most severely affected joint. Eight of 16 horses with unilateral OC underwent arthroscopy. The overall outcome was 'poor'. Only 15.4% (4/26) of potential race horses started a race, whereas 67% (4/6) non-racehorses were 'sound' for the intended use. Statistical analysis evaluating the effect of breed on outcome showed a statistically significant difference. There were no significant interactions between outcome and gender, affected limb, unilateral versus bilateral involvement, treatment or severity of the radiographic lesion. However, radiographic lesion severity on the humerus and glenoid showed significant positive correlation. CLINICAL SIGNIFICANCE: The overall poor prognosis for shoulder OC in young horses appears to be, in part, dependent on breed and intended use. There was not any difference in outcome between surgically and conservatively treated horses.

Education for contraceptive use by women after childbirth.

BACKGROUND: n 1966, the Population Council (a non-profit, non-government organisation which aims to foster reproductive health around the world) sponsored demonstration projects (known as the 'International Postpartum Program') on postpartum family planning, focussing primarily on developing countries and including 25 hospitals in 14 countries (Zatuchni 1970). These projects were based on the assumptions that women are receptive to family planning education in the postpartum period, and that they will not return to health centres for contraception once they have been discharged from hospital. The demonstration projects were declared a success given their ability to reach large numbers of women, and they were expanded to include hospitals in 21 countries (Winikoff et al 1991). Randomised controlled trials were not used to assess the effectiveness of the program. The provision of education on contraceptive use to postpartum mothers has come to be considered a standard component of postnatal care, with up to 84% of women noting that a discussion on contraception took place with a midwife on the postnatal floor (Glasier et al 1996). Although education frequently is provided as an integral component of discharge planning, many women experience this as a perfunctory discussion included as part of a checklist of topics (Glasier et al 1996). Midwifery and obstetric texts routinely refer to the provision of such education as a responsibility in the provision of postpartum care; however, the effectiveness of this intervention is seldom questioned (Keith et al 1980; Semeraro 1996). Questions have been raised about the assumptions that are the basis for such programs, e.g. that postpartum women are motivated to use contraception and that they will not return to a health centre for family planning advice (Winikoff et al 1991). In addition surveys conducted postpartum indicate that women may wish to discuss contraception antenatally and post hospital discharge, preferably in the context of general education about maternal and child health (Ozvaris 1997). OBJECTIVES: Postpartum education on contraceptive use is a routine component of discharge planning in many different countries with a wide variety of health care systems. This education is based on assumptions concerning women's receptivity to contraceptive education during the postpartum period and their presumed lack of access to such education after that time. The objective of this review is to assess the effects of education about contraceptive use to postpartum mothers. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, Psychlit, Popline, citations indexes and reference lists of relevant articles. We contacted subject experts to locate additional research, in addition to the Group's Specialised Register of Controlled Trials. Date of the most recent search: March 2001. SELECTION CRITERIA: Trials using random or quasi-random methods of allocation which evaluated the effectiveness of postpartum education about contraceptive use. DATA COLLECTION AND ANALYSIS: Two independent reviewers abstracted data on trial characteristics and results. MAIN RESULTS: No new trials were identified since this review was updated in 1999. Three trials were identified with 5438 women. These trials were conducted in Lebanon, Peru and Nepal. None of the trials examined all major prespecified endpoints. Postpartum education about contraceptive use influenced short-term use assessed between 40 days and three months post-partum. Women in the intervention groups were less likely to be non-users than women in the comparison groups (Odds Ratio (OR) = 0.47, 95% Confidence Interval (CI) 0.39 to 0.58). This benefit was not apparent following analysis of data from better quality studies (OR = 0.67, 95% CI 0.41 to 1.13). An apparent benefit on contraceptive use at six months post-partum (OR = 0.52, 95% CI 0.37 to 0.74) was not apparent following sensitivity analyses (OR = 0.59, 95% CI 0.33 to 1.06). Data are inadequate to assess the impact on cessation of breast feeding and non-attendance at family planning clinics. Unplanned pregnancies, knowledge about contraception and satisfaction with care were not assessed in any trial. REVIEWER'S CONCLUSIONS: The effectiveness of postpartum education about contraceptive use has not yet been established in randomised controlled trials. Such education may be effective in increasing the short-term use of contraception. However, there are only limited data examining a more-important longer-term effect on the prevention of unplanned pregnancies. Research needs to be undertaken to assess the effectiveness of the minimalist education provided in more developed countries and the variety of programs provided in less developed regions. Such research should examine the content, timing, range and organisation of postpartum education on contraceptive use including lactational amenorrhea, as well as its impact on breast feeding rates.

La línea que divide la insanidad y la perversidad / The line that divide illness and perversity

La antiquísima pregunta sobre la maldad o la locura es re-explorada. Esto parece estar permanentemente justificado en el servicio de una sociedad humana y sensible que necesita estar siempre consciente de las motivaciones y tendencias para concretizar nuestras ideas en forma conveniente. Esta área del pensamiento es abordada con un enfoque influenciado por el pragmatismo social contenido en los últimos escritos de Wittgenstein. Conceptos como justicia, maldad, insanidad o locura y si mismo son inevitablemente conceptos de una sociedad humana, como también lo es la equidad. Sin embargo la paradoja se hace evidente en algunos casos que se discuten, especialmente relevantes para algunas personas que deben ser encarceladas

Sociobiología y psiquiatría / Sociobiology and psychiatry

Desde la perspectiva de nuestra vida intelectual, debemos intentar calzar dentro del patrón total de las cosas y por cierto, dentro del mundo material y biológico. La sociobiología es parte del intento por hacerlo, pero en un sentido de abajo hacia arriba. Toma la forma, en que actualmente vemos el mundo de la física y de la química y también de la biología, y espera encajar nuestra sociología en ellos. Lo que recuerda uno de los comentarios Wittgenstein, que si quieres abrir una puerta debes mantener las bisagras inmóviles. Los sociobiólogos sostienen sus principios físicos inmoviles y ajustan explicaciones de nosotros para calzarlas con ellos. Otra manera de aprender sobre las cosas y producir teoría es lo que podriamos llamar de arriba a abajo. (Top Down). Uno sostiene firme lo que uno ve que son las personas y las sociedades, conscientes, esquemáticas, aparentemente libres y contemplativas. Uno no espera ser capaz de producir una teoría totalmente consistente y coherente a costa de evitar correspondencia con lo que parece ser observado. Uno nota los errores que surgirían en algunas extrapolaciones de las visiones de Newton y Euclides y anticipa algo similar para Darwin. Como lo dijera Einstein, el mundo es más complicado de lo que creimos, y probablemente más de lo que pensamos. Debemos, sin embargo, dejar de pensar o continuar tratando de integrar nuestras ideas de manera, al menos, análoga a aquellas de los sociobiológos. Quizás podríamos administrar nuestras sociedades mejor si estuviéramos conscientes y fuéramos humildes a causa de nuestra ignorancia, pero no debemos quedarnos intelectualmente paralizados por el escepticismo

Users' satisfaction with mental health services.

The opinion and level of satisfaction of the users of three different mental health services are presented as a way of evaluating the outcome of institutional and community approaches to psychiatric services. The information was collected in the cities of Concepcion (Chile), Sheffield (England) and Trieste (Italy) interviewing a sample of the users of the psychiatric services using a questionnaire specifically designed to suit the study's aims. The patients in Sheffield tended to support an eventual move towards a more community based service while the relatives appeared more interested in a general improvement of the traditional institutional facilities. In Trieste, patients as well as relatives are fully supportive of the community based services and reasonably aware of the difficulties. They want to improve things in the community. Finally, Chilean users show a considerable adherence to the more traditional and institutionalised ways of offering services and the levels of satisfaction were very high considering the conditions in which the help was delivered.

Attitudes of professional mental health workers to psychiatry.

An attempt is presented to measure and compare attitudes to and ideas about psychiatry and mental health services in Concepcion, Sheffield and Trieste. These cities have in some respects comparable populations but very different mental health services. Questionnaires in English, Italian and Spanish were used to assess the views of professional workers in the field. The information collected showed that the Italian professionals had the highest level of satisfaction with their work, showed most tolerance of deviant behaviour in the community, the least acceptance of diminished responsibility in law and a non-traditional view of psychiatry. Clearly Chilean professionals held a very traditional view and medicalised approach to mental illness but an encouraging theoretical approval towards eventual changes in the services, along with the lowest level of satisfaction with their work. Professionals from Sheffield held an intermediate position coming closer to the theoretical view of the Chileans but nearer to the Italian praxis and therapeutic approach.

Mentally abnormal homicide--a review of a special hospital male population.

The clinical, criminological and demographic characteristics of a Special Hospital population of male patients convicted of homicide are described. The results confirm much previous work on mentally abnormal homicide. Typically the patients come from a disadvantaged social background with poor employment records, a prior history of aggressive behaviour and a diagnosis of schizophrenia. Victims were usually known to the patient and often came from within his circle of family and friends. Only 25% of the patients were receiving treatment at the time of the offence. These findings are discussed in the light of the current literature.

Patterns of benzodiazepine use in Great Britain as measured by a general population survey.

In a general population survey by Gallup in Great Britain of 4148 subjects, 7.7% had taken benzodiazepines within the last year (male:female ratio 106:212). Younger subjects tended to take anxiolytics for shorter periods compared with older subjects, who often took hypnotics chronically. This pattern was most marked among females. Dosage escalation, tolerance, high daily dose usage, and hoarding were not common. A substantial proportion of current users had experienced difficulty in stopping their medication. Withdrawal problems were associated with being older than 45 years and consuming benzodiazepines for over 12 months. This lends support to the idea of benzodiazepine dependency. However, the appropriateness of long-term therapy for chronic symptoms cannot be ruled out.

Castilla del Pino's contribution to a scientific psychopathology.

This paper attempts to express critically the basic concepts in the extensive writings on psychopathology of the Spanish author, Castilla del Pino. These are otherwise only available to the world in Castilian. His work offers a way in which the course and depth of psychotic disorders could be charted mathematically. It illustrates the fact that, what is apparently objective is still necessarily so within the confines of the conventions of our languages, from which we cannot ever escape. He nevertheless shows how psychopathology is not therefore fundamentally different from other sciences, even if its development remains rudimentary.

Literature on methadone maintenance clinics.

The literature on the impact of methadone maintenance clinics is presented and it is pointed out that only a very tentative evaluation can be made. The authors themselves, however, are opposed to these clinics based on the balance of the evidence available.