Suboptimal performance of rotavirus testing in a vaccinated community population should prompt laboratories to review their rotavirus testing algorithms in response to changes in disease prevalence

Rotavirus vaccine has reduced disease prevalence in many countries. Consequently, we aimed to assess the reliability of a rotavirus immunoassay in the community population of Auckland and Northland, New Zealand. Between 22 October 2015 and 31 December 2016, 2873 fecal samples were tested by enzyme immunoassay (EIA, Rotascreen II, Microgen, UK) from 2748 patients (median age 8?years, range 0–101?years). Eighty-nine (3.1%) samples were reactive; 86 samples were tested by a second method. Rotavirus was confirmed in 49/86 (57%). Positive rotavirus EIAs were more likely to be confirmed in samples from cases ≥1?year of age (positive predictive value [PPV] 61%, 95% confidence interval [CI] 50–72%, P?=?0.049) and in spring/summer (PPV 67%, 95% CI 55–78%, P?=?0.003). Reactive rotavirus tests required confirmatory testing regardless of demographic, vaccine, or seasonal factors; a review of rotavirus testing algorithms may be necessary in other vaccinated community populations.     

Transfusion-transmitted malaria: current donor selection guidelines are not sufficient

A case of transfusion-transmitted malaria was identified in a 50-year-old male patient with sickle cell disease. The donor was Ghanaian, but had migrated to the UK some years previously and had not left the UK for 8 years. The donor met all of the extant donor selection guidelines [1] and a donation was consequently collected. However, on subsequent investigation of the case, the donor was found to be parasitaemic and have high titre malarial antibodies. As a result of this case, changes to the United Kingdom donor selection guidelines have been proposed. These changes will prevent any such further transmissions.     

Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy

Glial cells actively participate in synaptic transmission. They clear molecules from the synaptic cleft, receive signals from neurons and, in turn, release molecules that can modulate signaling between neuronal elements. Whether glial-derived transmitters can contribute to enduring changes in postsynaptic efficacy, however, remains to be established. In rat hypothalamic paraventricular nucleus, we demonstrate an increase in the amplitude of miniature excitatory postsynaptic currents in response to norepinephrine that requires the release of ATP from glial cells. The increase in quantal efficacy, which likely results from an insertion of AMPA receptors, is secondary to the activation of P2X(7) receptors, an increase in postsynaptic calcium and the activation of phosphatidylinositol 3-kinase. The gliotransmitter ATP, therefore, contributes directly to the regulation of postsynaptic efficacy at glutamatergic synapses in the CNS.     

Serum interferon inhibitor declines in patients with HIV-1 infection after a change in antiretroviral therapy

An inhibitor of interferon antiviral activity, which is absent in healthy HIV-seronegative persons, was detected in the sera of all 29 HIV-seropositive study participants. The relationship of the level of interferon inhibitor to CD4 count and HIV-RNA copy number was statistically significant in distinct models. Levels of interferon inhibitor declined by an average of 41-60% in patients who underwent a change in anti-retroviral therapy. Interferon inhibitor levels appear to decline as CD4 cell count rises and HIV-RNA levels fall. This suggests that interferon inhibitor may have a significant role in the host immune response to HIV infection.     

Acute exercise decreases airway inflammation, but not responsiveness, in an allergic asthma model

Previous studies have suggested that the asthmatic responses of airway inflammation, remodeling, and hyperresponsiveness (AHR) are interrelated; in this study, we used exercise to examine the nature of this interrelationship. Mice were sensitized and challenged with ovalbumin (OVA); mice were then exercised via running on a motorized treadmill at a moderate intensity. Data indicate that, within the lungs of OVA-treated mice, exercise attenuated the production of inflammatory mediators, including chemokines KC, RANTES, and MCP-1 and IL-12p40/p80. Coordinately, OVA-treated and exercised mice displayed decreases in leukocyte infiltration, including eosinophils, as compared with sedentary controls. Results also show that a single bout of exercise significantly decreased phosphorylation of the NFkappaB p65 subunit, which regulates the gene expression of a wide variety of inflammatory mediators. In addition, OVA-treated and exercised mice exhibited decreases in the levels of Th2-derived cytokines IL-5 and IL-13 and the prostaglandin PGE(2), as compared with sedentary controls. In contrast, results show that a single bout of exercise had no effect on AHR in OVA-treated mice challenged with increasing doses of aerosolized methacholine (0-50 mg/ml) as compared with sedentary mice. Exercise also had no effect on epithelial cell hypertrophy, mucus production, or airway wall thickening in OVA-treated mice as compared with sedentary controls. These findings suggest that a single bout of aerobic exercise at a moderate intensity attenuates airway inflammation but not AHR or airway remodeling in OVA-treated mice. The implication of these findings for the interrelationship between airway inflammation, airway remodeling, and AHR is discussed.     

Remote monitoring of lower-limb prosthetic socket fit using wireless technologies

Accurate fitting of a lower-limb prosthetic socket is the most important factor affecting amputee satisfaction and rehabilitation. The technology is now available to allow real-time monitoring of in-service pressure distribution of prosthetic limbs. This paper proposes a remote interfacial pressure monitoring system necessary for the assessment of fit. The suitability of a wireless ZigBee network due to its relevant technical specification is investigated. The system enables remote monitoring of a prosthetic socket and its fit under different operating conditions thereby improving design, efficiency and effectiveness. The data can be used by prosthetists and may also be recorded for future training or for patient progress monitoring. This can minimize the number of iterations by getting it right first time, thereby minimizing the number of replacement prostheses.     

Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo

The potential to differentiate human embryonic stem cells (hESCs) in vitro to provide an unlimited source of human hepatocytes for use in biomedical research, drug discovery, and the treatment of liver diseases holds great promise. Here we describe a three-stage process for the efficient and reproducible differentiation of hESCs to hepatocytes by priming hESCs towards definitive endoderm with activin A and sodium butyrate prior to further differentiation to hepatocytes with dimethyl sulfoxide, followed by maturation with hepatocyte growth factor and oncostatin M. We have demonstrated that differentiation of hESCs in this process recapitulates liver development in vivo: following initial differentiation, hESCs transiently express characteristic markers of the primitive streak mesendoderm before turning to the markers of the definitive endoderm; with further differentiation, expression of hepatocyte progenitor cell markers and mature hepatocyte markers emerged sequentially. Furthermore, we have provided evidence that the hESC-derived hepatocytes are able to carry out a range of hepatocyte functions: storage of glycogen, and generation and secretion of plasma proteins. More importantly, the hESC-derived hepatocytes express several members of cytochrome P450 isozymes, and these P450 isozymes are capable of converting the substrates to metabolites and respond to the chemical stimulation. Our results have provided evidence that hESCs can be differentiated efficiently in vitro to functional hepatocytes, which may be useful as an in vitro system for toxicity screening in drug discovery.     

PAX3–FOXO1 is essential for tumour initiation and maintenance but not recurrence in a human myoblast model of rhabdomyosarcoma

The PAX3–FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline‐inducible PAX3–FOXO1 and constitutive MYCN expression constructs were introduced into immortalized human myoblasts. Although myoblasts expressing PAX3–FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3–FOXO1 and MYCN expression resulted in transformation. Following intramuscular injection into immunodeficient mice, myoblasts expressing PAX3–FOXO1 and MYCN formed rapidly growing RMS tumours, whereas myoblasts expressing only PAX3–FOXO1 formed tumours after a longer latency period. Doxycycline withdrawal in myoblasts expressing inducible PAX3–FOXO1 and constitutive MYCN following tumour formation in vivo or focus formation in vitro resulted in tumour regression or smaller foci associated with myogenic differentiation and cell death. Following regression, most tumours recurred in the absence of doxycycline. Analysis of recurrent tumours revealed a subset without PAX3–FOXO1 expression, and cell lines derived from these recurrent tumours showed transformation in the absence of doxycycline. The doxycycline‐independent oncogenicity in these recurrent tumour‐derived lines persisted even after PAX3–FOXO1 was inactivated with a CRISPR/Cas9 editing strategy. Whereas cell lines derived from primary tumours were dependent on PAX3–FOXO1 and differentiated following doxycycline withdrawal, recurrent tumour‐derived cells without PAX3–FOXO1 expression did not differentiate under these conditions. These findings indicate that PAX3–FOXO1 collaborates with MYCN during early RMS tumourigenesis to dysregulate proliferation and inhibit myogenic differentiation and cell death. Although most cells in the primary tumours are dependent on PAX3–FOXO1, recurrent tumours can develop by a PAX3–FOXO1‐independent mechanism, in which rare cells are postulated to acquire secondary transforming events that were activated or selected by initial PAX3–FOXO1 expression. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.     

The Etiology of Stability and Change in Religious Values and Religious Attendance

Studies have demonstrated little to no heritability for adolescent religiosity but moderate genetic, shared environmental, and nonshared environmental influences on adult religiosity. Only one longitudinal study of religiosity in female twins has been conducted (Koenig et al., Dev Psychol 44:532?C543, 2008), and reported that persistence from mid to late adolescence is due to shared environmental factors, but persistence from late adolescence to early adulthood was due to genetic and shared environmental factors. We examined the etiology of stability and change in religious values and religious attendance in males and females during adolescence and early adulthood. The heritability of both religious values and religious attendance increased from adolescence to early adulthood, although the increase was greater for religious attendance. Both genetic and shared environmental influences contributed to the stability of religious values and religious attendance across adolescence and young adulthood. Change in religious values was due to both genetic and nonshared environmental influences specific to early adulthood, whereas change in religious attendance was due in similar proportions to genetic, shared environmental, and non-shared environmental influences.