Role of lactobacilli and lactoferrin in the mucosal cervicovaginal defense

Human lactoferrin is an iron-binding glycoprotein present at high concentrations in breast milk and colostrum. It is produced by many exocrine glands and widely distributed in a variety of body fluids. This protein has antimicrobial, immunomodulatory, antioxidant, and anticancer properties. Two important hLf receptors have been identified: LDL receptor related protein (LRP1), a low specificity receptor, and intelectin-1 (ITLN1), a high specificity receptor. No data are present on the role of hLf on the biliary epithelium. Our aims have been to evaluate the expression of Lf and its receptors in human and murine cholangiocytes and its effect on proliferation. Immunohistochemistry and immunofluorescence (IF) were conducted on human healthy and primary biliary cholangitis (PBC) liver samples as well as on liver samples obtained from normal and bile duct ligated (BDL) mice to evaluate the expression of Lf, LRP1 and ITLN1. Cell proliferation in vitro studies were performed on human cholangiocyte cell lines via 3-(4,5-dimetiltiazol-2-il)-2,5-diphenyltetrazolium assay as well as IF to evaluate proliferating cell nuclear antigen (PCNA) expression. Our results show that mouse and human cholangiocytes express Lf, LRP1 and ITLN1, at higher extent in cholangiocytes from BDL and PBC samples. Furthermore, the in vitro addition of bovine Lf (bLf) has a proliferative effect on human cholangiocyte cell line. The results support a proliferative role of hLf on the biliary epithelium; this pro-proliferative effect of hLf and bLf on cholangiocytes could be particularly relevant in human cholangiopathies such as PBC, characterized by cholangiocyte death and ductopenia

Diversification of importin-α isoforms in cellular trafficking and disease states.

The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases

The Time is Gone!? Pink Floyds "Time" (1973)

This paper provides a hermeneutic approach on Pink Floyds popular song "Time" from 1973s album Dark Side Of The Moon. The primary aim of this examination is the analysis of the conceptual connection of music and lyrics in this song. Moreover, derivation of semantic meaning potential is used to form an intersubjectively verifiable song interpretation. All in all, the main results of this analysis suggest a close connection of the songs musical parameters, i.e. form, harmony, melody, rhythm as well as sound, and its lyrical theme: (1) first the musique concrète in the songs introduction and the subsequent instrumental passage establish evident semantic relations to the following lyrical theme of fleeting time, (2) a devils circle of transitoriness of life is presented in the songs lyrics and is musically mirrored by periodic formal and harmonic repetitions, (3) the ambivalence of the bridges negative lyrics in combination with the sweet melodic thirds in the vocals suggests a melancholic atmosphere, (4) the lyrics description of a human life from birth to death is reflected in the formal structure and the harmony of »Time« as well as in the conceptual arrangement of Dark Side Of The Moons first LP-side from »Speak To Me« to »The Great Gig In The Sky«

Further reflections on the temporality of energy transitions: a response to critics

In tandem with the call for more careful, thoughtful, reflexive thinking on the topic of energy transitions, in this paper we attempt to unpack some of the themes advanced in this Debate. We begin by investigating the multi-dimensionality of energy transitions as well as transition speeds for different parts of energy systems at different scales. We then call on analysts to consider transition speeds and scalar levels. We also argue for focusing on accelerated diffusion driven by rapid changes in cost, improvements in technology, or other factors

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

In healthy circumstances the immune system coordinates tissue repair responses in a tight balance that entails efficient inflammation for removal of potential threats, proper wound closure, and regeneration to regain tissue function. Pathological conditions, continuous exposure to noxious agents, and even ageing can dysregulate immune responses after injury. This dysregulation can lead to a chronic repair mechanism known as fibrosis. Alterations in wound healing can occur in many organs, but our focus lies with the lung as it requires highly regulated immune and repair responses with its continuous exposure to airborne threats. Dysregulated repair responses can lead to pulmonary fibrosis but the exact reason for its development is often not known. Here, we review the diversity of innate immune cells of myeloid origin that are involved in tissue repair and we illustrate how these cell types can contribute to the development of pulmonary fibrosis. Moreover, we briefly discuss the effect of age on innate immune responses and therefore on wound healing and we conclude with the implications of current knowledge on the avenues for future research

Trends in paediatric practice in Australia: 2008 and 2013 national audits from the Australian Paediatric Research Network

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135978/1/jpc13280_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135978/2/jpc13280.pd

An overview of the clinical use of filter paper in the diagnosis of tropical diseases.

Tropical infectious diseases diagnosis and surveillance are often hampered by difficulties of sample collection and transportation. Filter paper potentially provides a useful medium to help overcome such problems. We reviewed the literature on the use of filter paper, focusing on the evaluation of nucleic acid and serological assays for diagnosis of infectious diseases using dried blood spots (DBS) compared with recognized gold standards. We reviewed 296 eligible studies and included 101 studies evaluating DBS and 192 studies on other aspects of filter paper use. We also discuss the use of filter paper with other body fluids and for tropical veterinary medicine. In general, DBS perform with sensitivities and specificities similar or only slightly inferior to gold standard sample types. However, important problems were revealed with the uncritical use of DBS, inappropriate statistical analysis, and lack of standardized methodology. DBS have great potential to empower healthcare workers by making laboratory-based diagnostic tests more readily accessible, but additional and more rigorous research is needed

A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women.

Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health messages about possible adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 g (low discontinued) to 184 g of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of risk to the unborn child. Further, specific maternal characteristics were associated with different trajectories, which may inform targeted health promotion aimed at reducing alcohol use in pregnancy

Interleukin-8 predicts fatigue at 12 months post-injury in children with traumatic brain injury

Despite many children experiencing fatigue after childhood brain injury, little is known about the predictors of this complaint. To date, traditional indices of traumatic brain injury (TBI) severity have not reliably predicted persisting fatigue (up to 3 years post‐injury). This study aimed to establish if persisting fatigue is predicted by serum biomarker concentrations in child TBI. We examined if acute serum biomarker expression would improve prediction models of 12‐month fatigue based on injury severity. Blood samples were collected from 87 children (1 – 17 years at injury) sustaining mild to severe TBI (GCS range 3‐15; mean 12.43; classified as mild TBI (n=50, 57%) vs moderate/severe TBI n=37, 43%), and presenting to the Emergency Departments (ED) and Pediatric Intensive Care Units (PICU) at one of three tertiary pediatric hospitals (Royal Children’s Hospital (RCH); Hospital for Sick Children (HSC), Toronto St Justine Children’s Hospital (SJH), Montreal). Six serum biomarker concentrations were measured within 24 hours of injury [interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), soluble vascular cell adhesion molecule (SVCAM), S100 calcium binding protein B (S100B), neuron specific enolase (NSE), and soluble neural cell adhesion molecule (sNCAM)]. Fatigue at 12 months post‐injury was measured using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (parent report), classified as present/absent using previously derived cut‐points. At 12 months post‐injury, 22% of participants experienced fatigue. A model including interleukin‐8 (IL‐8) was the best serum biomarker for estimating the probability of children experiencing fatigue at 12 months post‐injury. IL‐8 also significantly improved predictive models of fatigue based on severity