HLA-G and malaria in pregnancy

© 2011 Dr. Kylie HorneHLA-G is an atypical class I MHC molecule that promotes tolerance and attenuates the immune response. It is highly expressed on the placental cells that invade the maternal tissues, and is one of the ways in which the immune system is modified in pregnancy to allow maternal tolerance of the foetus. The modification of the maternal immune response may also inadvertently promote tolerance of infections in pregnancy, and HLA-G may contribute to this tolerance of infection. Malaria is an infectious disease with high rates of morbidity and mortality globally. The most severe form is caused by the parasite Plasmodium falciparum. In endemic areas it is primarily a disease of children. Immunity is gradually acquired and disease amongst adults is uncommon. However during pregnancy, the high rates of infection return. Malaria in pregnancy is associated with morbidity and mortality for the mother and the foetus. This study is based on the hypothesis that the immune changes in pregnancy that allow maternal tolerance of the foetus may also contribute to the increased rate of malaria in pregnancy. It contributes to the understanding of the pathology of malaria in pregnancy, but also to the knowledge of the immunological response to malaria, of the role of HLA-G in response to infection and how the changes in placental immunology may contribute to other infections in the placenta. This study shows there is an association between HLA-G genotype and Plasmodium falciparum infection in the placenta, that genotype only corresponds with mRNA for a specific pattern of malaria infection in the placenta, and that HLA-G expression correlates with an important consequence of malaria in pregnancy, low birth weight. These findings suggest the hypothesis that placentae that can quickly reduce their HLA-G expression are able to mount a more efficient immune response to the pathogen. Those who have a persistently elevated HLA-G are unable to mount an efficient immune response, and develop a chronic infection. The study also demonstrates a reduction in cytokine response to Plasmodium falciparum in the presence of placental cells, although this is not mediated by HLA-G

Neural Tissue Engineering of the CNS Using Hydrogels

Current therapies have limited capacity to curtail disease progression or damage of the central nervous system (CNS) of adult mammals and successful regeneration following injury or disease does not occur. Regeneration of the CNS is limited by physical and chemical inhibitory barriers within the injured environment and the absence of positive cues that elicit and guide repair. Neural tissue engineering strategies focus on developing scaffolds that artificially generate favourable cellular microenvironments that attempt to tip the balance in favour of regeneration. Some recent advances using scaffolds to promote regeneration within the CNS, particularly in conjunction with stem cells, has generated promising results. This review focuses on hydrogel scaffolds which have been used extensively in neural tissue engineering applications and addresses the physical and chemical modifications of these materials to promote nerve regeneration

Surveillance of life-long antibiotics:A review of antibiotic prescribing practices in an Australian Healthcare Network

Abstract Background The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not \u201clife-long\u201d course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. Methods A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6\ua0month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. Results 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1\ua0year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. Conclusion Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged courses of antibiotics were used mainly to suppress infections thought incurable, but also as primary and secondary prophylaxis and as anti-inflammatory agents. More research is needed to understand the impact of long-term antibiotic consumption on both patients and microbial ecology

Examining the Health and Wellness Costs Associated with Binge-watching Behaviors

The prevalence of binge-watching behavior is increasing as access to streaming entertainment media becomes more readily available (Flayelle, Maurage, Vögele, Karila, & Billieux, 2018). There is little research that exists examining binge-watching behaviors and health behaviors. Exelmans and Van den Bulk (2017) found correlations between binge-watching and certain maladaptive behaviors such as poor sleep quality. Along these lines, the first aim of the current study was to determine whether self-reported binge-watching behavior is related to self-reported health and health risk behaviors. In the current study these health behaviors included frequency of eating fast or restaurant foods, drinking alcohol, physical activity, fruit and vegetable intake, smoking, and perceived overall health. In addition to examining health risk behaviors the second aim of our study was to examine the correlation between self-reported binge-watching behaviors and social factors of wellness such as loneliness. Across these two aims, we predicted that high levels of binge-watching behaviors would predict less health behaviors, more health risk behaviors, and greater loneliness. Undergraduate participants (N=263) completed an online survey assessing their media habits and health and wellness variables. Our hypotheses were largely supported. Higher frequency of binge-watching predicted more impulsive and high-risk health behaviors such as eating fast food, drinking alcohol, and less physical activity. Binge-watching also correlated with lower perceived health and higher loneliness. The results of this study are useful in revealing a largely uninvestigated relationship between media watching habits, physical health, and wellness, and they contribute to our understanding of the detriments of binge-watching

Long-Term Outcomes in Patients on Life-Long Antibiotics: A Five-Year Cohort Study

Background: Little is known about the impacts at an individual level of long-term antibiotic consumption. We explored health outcomes of long-term antibiotic therapy prescribed to a cohort of patients to suppress infections deemed incurable. Methods: We conducted a 5-year longitudinal study of patients on long-term antibiotics at Monash Health, a metropolitan tertiary-level hospital network in Australia. Adults prescribed antibiotics for >12 months to suppress chronic infection or prevent recurrent infection were included. A retrospective review of medical records and a descriptive analysis was conducted. Results: Twenty-seven patients were followed up during the study period, from 29 patients originally identified in Monash Health in 2014. Seven of the 27 patients (26%) died from causes unrelated to the suppressed infection, six (22%) ceased long-term antibiotic therapy and two (7%) required treatment modification. Fifteen (56%) were colonised with multiresistant microorganisms, including vancomycin resistant Enterococci, methicillin resistant Staphylococcus aureus, and carbapenem resistant Enterobacteriaciae. Conclusions: This work highlights the potential pitfalls of long-term antibiotic therapy, and the frailty of this cohort, who are often ineligible for definitive curative therapy

Acoustic microstreaming increases the efficiency of reverse transcription reactions comprising single-cell quantities of RNA

Correlating gene expression with behavior at the single-cell level is difficult, largely because the small amount of available mRNA (<1 pg) degrades before it can be reverse transcribed into a more stable cDNA copy. This study tested the capacity for a novel acoustic microstreaming method (“micromixing”), which stirs fluid at microliter scales, to improve cDNA yields from reverse transcription (RT) reactions comprising single-cell quantities of RNA. Micromixing significantly decreased the number of qPCR cycles to detect cDNA representing mRNA for hypoxanthine phosphoribosyl-transferase (Hprt) and nuclear receptor–related 1 (Nurr1) by ~9 and ~15 cycles, respectively. The improvement was equivalent to performing RT with 10- to 100-fold more cDNA in the absence of micromixing. Micromixing enabled reliable detection of the otherwise undetectable, low-abundance transcript, Nurr1. It was most effective when RNA concentrations were low (0.1–1 pg/µL, a “single-cell equivalent”) but had lesser effects at higher RNA concentrations (~1 ng/µL). This was supported by imaging experiments showing that micromixing improved mixing of a low concentration (20 pg/µL) of fluorescence-labeled RNA but not a higher concentration (1 ng/µL). We conclude that micromixing significantly increases RT yields obtainable from single-cell quantities of RNA