Context Is key: Delineating the unique functions of IFNα and IFNβ in disease

Type I interferons (IFNs) are critical effector cytokines of the immune system and were originally known for their important role in protecting against viral infections; however, they have more recently been shown to play protective or detrimental roles in many disease states. Type I IFNs consist of IFNα, IFNβ, IFNϵ, IFNκ, IFNω, and a few others, and they all signal through a shared receptor to exert a wide range of biological activities, including antiviral, antiproliferative, proapoptotic, and immunomodulatory effects. Though the individual type I IFN subtypes possess overlapping functions, there is growing appreciation that they also have unique properties. In this review, we summarize some of the mechanisms underlying differential expression of and signaling by type I IFNs, and we discuss examples of differential functions of IFNα and IFNβ in models of infectious disease, cancer, and autoimmunity

Parentage of Hydatidiform Moles

We were presented with the STR (short tandem repeat) profiles from two separate paternity trios. Each trio consisted of a mother, an alleged father, and products of conception (POC) that contained a hydatidiform mole but no visible fetus. In both cases, antecedent pregnancies had followed alleged sexual assaults. Mole classification and pathogenesis are described in order to explain the analyses and statistical reasoning used in each case. One mole exhibited several loci with two different paternal alleles, indicating it was a dispermic (heterozygous) mole. Maternal decidua contaminated the POC, preventing the identification of paternal obligate alleles (POAs) at some loci. The other mole exhibited only one paternal allele/locus at all loci and no maternal alleles, indicating it was a diandric and diploid (homozygous) mole. In each case, traditional calculations were used to determine paternity indices (PIs) at loci that exhibited one paternal allele/locus. PIs at mole loci with two different paternal alleles/locus were calculated from formulas first used for child chimeras that are always dispermic. Combined paternity indices in both mole cases strongly supported the paternity of each suspect.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155886/1/jfo14291.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155886/2/jfo14291_am.pd

Perceived barriers and facilitators to mental health help-seeking in young people: a systematic review

<p>Abstract</p> <p>Background</p> <p>Adolescents and young adults frequently experience mental disorders, yet tend not to seek help. This systematic review aims to summarise reported barriers and facilitators of help-seeking in young people using both qualitative research from surveys, focus groups, and interviews and quantitative data from published surveys. It extends previous reviews through its systematic research methodology and by the inclusion of published studies describing what young people themselves perceive are the barriers and facilitators to help-seeking for common mental health problems.</p> <p>Methods</p> <p>Twenty two published studies of perceived barriers or facilitators in adolescents or young adults were identified through searches of PubMed, PsycInfo, and the Cochrane database. A thematic analysis was undertaken on the results reported in the qualitative literature and quantitative literature.</p> <p>Results</p> <p>Fifteen qualitative and seven quantitative studies were identified. Young people perceived stigma and embarrassment, problems recognising symptoms (poor mental health literacy), and a preference for self-reliance as the most important barriers to help-seeking. Facilitators were comparatively under-researched. However, there was evidence that young people perceived positive past experiences, and social support and encouragement from others as aids to the help-seeking process.</p> <p>Conclusions</p> <p>Strategies for improving help-seeking by adolescents and young adults should focus on improving mental health literacy, reducing stigma, and taking into account the desire of young people for self-reliance.</p

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Cost calculation and prediction in adult intensive care: A ground-up utilization study

Publisher's copy made available with the permission of the publisherThe ability of various proxy cost measures, including therapeutic activity scores (TISS and Omega) and cumulative daily severity of illness scores, to predict individual ICU patient costs was assessed in a prospective “ground-up” utilization costing study over a six month period in 1991. Daily activity (TISS and Omega scores) and utilization in consecutive admissions to three adult university associated ICUs was recorded by dedicated data collectors. Cost prediction used linear regression with determination (80%) and validation (20%) data sets. The cohort, 1333 patients, had a mean (SD) age 57.5 (19.4) years, (41% female) and admission APACHE III score of 58 (27). ICU length of stay and mortality were 3.9 (6.1) days and 17.6% respectively. Mean total TISS and Omega scores were 117 (157) and 72 (113) respectively. Mean patient costs per ICU episode (1991 $AUS) were$6801 ($10311), with median costs of$2534, range $106 to$95,602. Dominant cost fractions were nursing 43.3% and overheads 16.9%. Inflation adjusted year 2002 (mean) costs were $9343 ($ AUS). Total costs in survivors were predicted by Omega score, summed APACHE III score and ICU length of stay; determination R2, 0.91; validation 0.88. Omega was the preferred activity score. Without the Omega score, predictors were age, summed APACHE III score and ICU length of stay; determination R2, 0.73; validation 0.73. In non-survivors, predictors were age and ICU length of stay (plus interaction), and Omega score (determination R2, 0.97; validation 0.91). Patient costs may be predicted by a combination of ICU activity indices and severity scores.J. L. Moran, A. R. Peisach, P. J. Solomon, J. Martinhttp://www.aaic.net.au/Article.asp?D=200403

The relationship between early neural responses to emotional faces at age 3 and later autism and anxiety symptoms in adolescents with autism

Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent and later ASD and anxiety symptoms. Greater response amplitude to fearful faces corresponded to greater social communication difficulties at age 3, and less improvement by age 14. Faster ERPs to neutral faces predicted greater ASD symptom improvement over time, lower ASD severity in adolescence, and lower anxiety in adolescence. Early individual differences in processing of emotional stimuli likely reflect a unique predictive contribution from social brain circuitry early in life

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection

BACKGROUND: Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought. METHODOLOGY: Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFNγ, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay. CONCLUSIONS: Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni