High porosity metallic glass foam: A powder metallurgy route

A powder metallurgy route to the fabrication of metallic glass foam is introduced. The method involves consolidating metallic glass powder blended with blowing agent particulates to produce expandable precursors, capable of yielding foams with porosities as high as 86%. The foams are found to inherit the strength of the parent metallic glass and to be able to deform heavily toward full densification absorbing high amounts of energy

Ex vivo evaluation of mucosal responses to vaccination with ALVAC and AIDSVAX of non-human primates

Non-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured systemically. We assessed the mucosal responses elicited upon vaccination with ALVAC and AIDSVAX using ex vivo Rhesus macaque mucosal tissue explant models. Following booster immunization with ALVAC/AIDSVAX, anti-gp120 HIV-1CM244-specific IgG and IgA were detected in culture supernatant cervicovaginal and colorectal tissue explants, as well as systemically. Despite protection from ex vivo viral challenge, no neutralization was observed with tissue explant culture supernatants. Priming with ALVAC induced distinct cytokine profiles in cervical and rectal tissue. However, ALVAC/AIDSVAX boosts resulted in similar modulations in both mucosal tissues with a statistically significant decrease in cytokines linked to inflammatory responses and lymphocyte differentiation. With ALVAC/AIDSVAX boosts, significant correlations were observed between cytokine levels and specific IgA in cervical explants and specific IgG and IgA in rectal tissue. The cytokine secretome revealed differences between vaccination with ALVAC and ALVAC/AIDSVAX not previously observed in mucosal tissues and distinct from the systemic response, which could represent a biosignature of the vaccine combination

Early Divergent Host Responses in SHIVsf162P3 and SIVmac251 Infected Macaques Correlate with Control of Viremia

We previously showed intravaginal inoculation with SHIVsf162p3 results in transient viremia followed by undetectable viremia in most macaques, and some displayed subsequent immunity to superinfection with pathogenic SIVmac251. Here we compare early T cell activation, proliferation, and plasma cytokine/chemokine responses in macaques intravaginally infected with either SHIVsf162p3 or SIVmac251 to determine whether distinct differences in host responses may be associated with early viral containment. The data show SIVmac251 infection results in significantly higher levels of T cell activation, proliferation, and a mixed cytokine/chemokine “storm” in plasma in primary infection, whereas infection with SHIVsf162p3 resulted in significantly lower levels of T cell activation, proliferation, and better preservation of memory CD4+ T cells in early infection which immediately preceded control of viremia. These results support the hypothesis that early systemic immune activation, T cell proliferation, and a more prominent and broader array of cytokine/chemokine responses facilitate SIV replication, and may play a key role in persistence of infection, and the progression to AIDS. In contrast, immune unresponsiveness may be associated with eventual clearance of virus, a concept that may have key significance for therapy and vaccine design

'Like building a plane and flying it all in one go': an interview study of infection prevention and control in Australian general practice during the first 2 years of the SARS-CoV-2 pandemic.

OBJECTIVES: General practitioners (GPs) and their staff have been at the frontline of the SARS-CoV-2 pandemic in Australia. However, their experiences of responding to and managing the risks of viral transmission within their facilities are poorly described. The aim of this study was to describe the experiences, and infection prevention and control (IPC) strategies adopted by general practices, including enablers of and challenges to implementation, to contribute to our understanding of the pandemic response in this critical sector. DESIGN: Semistructured interviews were conducted in person, by telephone or online video conferencing software, between November 2020 and August 2021. PARTICIPANTS: Twenty general practice personnel working in New South Wales, Australia, including nine GPs, one general practice registrar, four registered nurses, one nurse practitioner, two practice managers and two receptionists. RESULTS: Participants described implementing wide-ranging repertoires of IPC strategies-including telehealth, screening of patients and staff, altered clinic layouts and portable outdoor shelters, in addition to appropriate use of personal protective equipment (PPE)-to manage the demands of the SARS-CoV-2 pandemic. Strategies were proactive, influenced by the varied contexts of different practices and the needs and preferences of individual GPs as well as responsive to local, state and national requirements, which changed frequently as the pandemic evolved. CONCLUSIONS: Using the 'hierarchy of controls' as a framework for analysis, we found that the different strategies adopted in general practice often functioned in concert with one another. Most strategies, particularly administrative and PPE controls, were subjected to human variability and so were less reliable from a human factors perspective. However, our findings highlight the creativity, resilience and resourcefulness of general practice staff in developing, implementing and adapting their IPC strategies amidst constantly changing pandemic conditions

Entanglements of affect, space, and evidence in pandemic healthcare: An analysis of Australian healthcare workers' experiences of COVID-19.

The COVID-19 pandemic continues to highlight both global interconnectedness and schisms across place, context and peoples. While countries such as Australia have securitised their borders in response to the global spread of disease, flows of information and collective affect continue to permeate these boundaries. Drawing on interviews with Australian healthcare workers, we examine how their experiences of the pandemic are shaped by affect and evidence 'traveling' across time and space. Our analysis points to the limitations of global health crisis responses that focus solely on material risk and spatial separation. Institutional responses must, we suggest, also consider the affective and discursive dimensions of health-related risk environments

Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects

Abstract Background In recent years, we have come to recognize that a multitude of in utero exposures have the capacity to induce the development of congenital and metabolic defects. As most of these encounters manifest their effects beyond the window of exposure, deciphering the mechanisms of teratogenesis is incredibly difficult. For many agents, altered epigenetic programming has become suspect in transmitting the lasting signature of exposure leading to dysgenesis. However, while several chemicals can perturb chromatin structure acutely, for many agents (particularly alcohol) it remains unclear if these modifications represent transient responses to exposure or heritable lesions leading to pathology. Results Here, we report that mice encountering an acute exposure to alcohol on gestational Day-7 exhibit significant alterations in chromatin structure (histone 3 lysine 9 dimethylation, lysine 9 acetylation, and lysine 27 trimethylation) at Day-17, and that these changes strongly correlate with the development of craniofacial and central nervous system defects. Using a neural cortical stem cell model, we find that the epigenetic changes arising as a consequence of alcohol exposure are heavily dependent on the gene under investigation, the dose of alcohol encountered, and that the signatures arising acutely differ significantly from those observed after a 4-day recovery period. Importantly, the changes observed post-recovery are consistent with those modeled in vivo, and associate with alterations in transcripts encoding multiple homeobox genes directing neurogenesis. Unexpectedly, we do not observe a correlation between alcohol-induced changes in chromatin structure and alterations in transcription. Interestingly, the majority of epigenetic changes observed occur in marks associated with repressive chromatin structure, and we identify correlative disruptions in transcripts encoding Dnmt1, Eed, Ehmt2 (G9a), EzH2, Kdm1a, Kdm4c, Setdb1, Sod3, Tet1 and Uhrf1. Conclusions These observations suggest that the immediate and long-term impacts of alcohol exposure on chromatin structure are distinct, and hint at the existence of a possible coordinated epigenetic response to ethanol during development. Collectively, our results indicate that alcohol-induced modifications to chromatin structure persist beyond the window of exposure, and likely contribute to the development of fetal alcohol syndrome-associated congenital abnormalities

Early Regeneration of Thymic Progenitors in Rhesus Macaques Infected with Simian Immunodeficiency Virus

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model of AIDS, we examined the early effects of SIV on the thymus. We found that thymic infection by SIV resulted in increased apoptosis 7–14 d after infection, followed by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte progenitors occurred by day 50 and was accompanied by increased levels of cell proliferation in the thymus. Our results demonstrate a marked increase in thymic progenitor activity very early in the course of SIV infection, long before marked declines in peripheral CD4+ T cell counts

Topically Applied Recombinant Chemokine Analogues Fully Protect Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge

Effective strategies for preventing human immunodeficiency virus infection are urgently needed, but recent failures in key clinical trials of vaccines and microbicides highlight the need for new approaches validated in relevant animal models. Here, we show that 2 new chemokine (C-C motif) receptor 5 inhibitors, 5P12-RANTES (regulated on activation, normal T cell expressed and secreted) and 6P4-RANTES, fully protect against infection in the rhesus vaginal challenge model. These highly potent molecules, which are amenable to low-cost production, represent promising new additions to the microbicides pipelin