Persistent effects of early infant diet and associated microbiota on the juvenile immune system.

Early infant diet has significant impacts on the gut microbiota and developing immune system. We previously showed that breast-fed and formula-fed rhesus macaques develop significantly different gut microbial communities, which in turn are associated with different immune systems in infancy. Breast-fed animals manifested greater T cell activation and proliferation and harbored robust pools of T helper 17 (TH17) cells. These differences were sustained throughout the first year of life. Here we examine groups of juvenile macaques (approximately 3 to 5 y old), which were breast-fed or formula-fed in infancy. We demonstrate that juveniles breast-fed in infancy maintain immunologic differences into the fifth year of life, principally in CD8(+) memory T cell activation. Additionally, long-term correlation networks show that breast-fed animals maintain persistent relationships between immune subsets that are not seen in formula-fed animals. These findings demonstrate that infant feeding practices have continued influence on immunity for up to 3 to 5 y after birth and also reveal mechanisms for microbial modulation of the immune system

Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir

Using a repeat-exposure macaque model, Walid Heneine and colleagues find that pre-exposure prophylaxis with combination antiretroviral drugs provides protection against rectal challenge with a SHIV virus

Role of CD8+ cells in controlling replication of nonpathogenic Simian Immunodeficiency Virus SIVmac1A11

Infection of macaques with the avirulent molecular clone SIVmac1A11 results in transient low viremia and no disease. To investigate if this low viremia is solely due to intrinsic poor replication fitness or is mediated by efficient immune-mediated control, 5 macaques were inoculated intravenously with SIVmac1A11. Three animals that were depleted of CD8+ cells at the start of infection had more prolonged viremia with peak virus levels 1 to 2 logs higher than those of 2 animals that received a non-depleting control antibody. Thus, CD8+ cell-mediated immune responses play an important role in controlling SIVmac1A11 replication during acute viremia

Overview and Strategy Analysis of Technology-Based Nonpharmacological Interventions for In-Hospital Delirium Prevention and Reduction:Systematic Scoping Review

BACKGROUND: Delirium prevention is crucial, especially in critically ill patients. Nonpharmacological multicomponent interventions for preventing delirium are increasingly recommended and technology-based interventions have been developed to support them. Despite the increasing number and diversity in technology-based interventions, there has been no systematic effort to create an overview of these interventions for in-hospital delirium prevention and reduction. OBJECTIVE: This systematic scoping review was carried out to answer the following questions: (1) what are the technologies currently used in nonpharmacological technology-based interventions for preventing and reducing delirium? and (2) what are the strategies underlying these currently used technologies? METHODS: A systematic search was conducted in Scopus and Embase between 2015 and 2020. A selection was made in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Studies were eligible if they contained any type of technology-based interventions and assessed delirium-/risk factor–related outcome measures in a hospital setting. Data extraction and quality assessment were performed using a predesigned data form. RESULTS: A total of 31 studies were included and analyzed focusing on the types of technology and the strategies used in the interventions. Our review revealed 8 different technology types and 14 strategies that were categorized into the following 7 pathways: (1) restore circadian rhythm, (2) activate the body, (3) activate the mind, (4) induce relaxation, (5) provide a sense of security, (6) provide a sense of control, and (7) provide a sense of being connected. For all technology types, significant positive effects were found on either or both direct and indirect delirium outcomes. Several similarities were found across effective interventions: using a multicomponent approach or including components comforting the psychological needs of patients (eg, familiarity, distraction, soothing elements). CONCLUSIONS: Technology-based interventions have a high potential when multidimensional needs of patients (eg, physical, cognitive, emotional) are incorporated. The 7 pathways pinpoint starting points for building more effective technology-based interventions. Opportunities were discussed for transforming the intensive care unit into a healing environment as a powerful tool to prevent delirium. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020175874; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=17587

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection.

BackgroundWe reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251) mutants with a K65R mutation in reverse transcriptase (RT), and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later.ResultsThe early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia.ConclusionThis is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses

Efficacy of HIV Postexposure Prophylaxis: Systematic Review and Meta-analysis of Nonhuman Primate Studies

Background. The efficacy of antiretrovirals as postexposure prophylaxis (PEP) to prevent viral acquisition was demonstrated in nonhuman primate models of human immunodeficiency virus (HIV) in the early 1990s. To complement the evidence base for efficacy of HIV PEP in humans, we systematically reviewed the published data on PEP efficacy across animal studies. Methods. PubMed, Web of Science, and Embase were searched from inception to 31 May 2014 for randomized and nonrandomized studies reporting seroconversions among uninfected animals exposed to HIV or simian immunodeficiency virus, irrespective of route of exposure. Seroconversion risk data were pooled using random-effects models, and associations explored through meta-regression. Results. Twenty-five studies (408 primates) were included for review. The risk of serconversion was 89% lower among animals exposed to PEP compared with those that did not receive PEP (odds ratio, 0.11 [95% confidence interval, .05-.23]). Heterogeneity was low (I2 = 0.0%). In meta-regression, a significant association was found between timing of PEP and seroconversion and the use of tenofovir compared with other drugs. Conclusions. This review provides further evidence of the protective benefit of PEP in preventing HIV acquisition, and the importance of initiating PEP as early as possible following virus exposur

Multi-level Access in Searchable Symmetric Encryption

Remote storage delivers a cost effective solution for data storage. If data is of a sensitive nature, it should be encrypted prior to outsourcing to ensure confidentiality; however, searching then becomes challenging. Searchable encryption is a well-studied solution to this problem. Many schemes only consider the scenario where users can search over the entirety of the encrypted data. In practice, sensitive data is likely to be classified according to an access control policy and different users should have different access rights. It is unlikely that all users have unrestricted access to the entire data set. Current schemes that consider multi-level access to searchable encryption are predominantly based on asymmetric primitives. We investigate symmetric solutions to multi-level access in searchable encryption where users have different access privileges to portions of the encrypted data and are not permitted to search over, or learn information about, data for which they are not authorised

The Influence of the Presentation of Camera Surveillance on Cheating and Pro-Social Behavior

Introduction: This study is aimed at gaining more insight into the effects of camera-surveillance on behavior. It investigates the effects of three different ways of “framing” camera presence on cheating behavior and pro-social behavior. First, we explore the effect of presenting the camera as the medium through which an intimidating authority watches the participant. Second, we test the effect of presenting the camera as being a neutral, non-intimidating viewer. Third, we investigate the effect of watching oneself via a camera. In contrast to most studies on camera surveillance, we will conduct our experiments in an indoor setting. We also explore possible interaction effects of personality traits; we measured Locus of Control, Need for Approval, Self-Monitoring and Social Value Orientation.Methods: In this experiment participated 86 students, randomly distributed over four conditions: three different ways of framing the camera presence, plus a control condition. Our main dependent variables were various kinds of cheating and pro-social behavior. We established the participant's relevant personality traits using a classification tree.Results: For cheating behavior, findings showed that in the “authorative” way of framing camera presence and in the situation in which participants viewed themselves, participants cheated significantly less compared to a situation without camera-surveillance. We did not find significant effects of camera surveillance on pro-social behavior. Looking at personality traits, we found an indication that people with an internal locus of control are more inclined to cheat when there is no camera present compared to people with an external locus of control. However, the effects of our manipulations were stronger.Conclusion: Our findings support the idea that the framing of a camera's presence does indeed influence cheating behavior, adding to the preventive effects of camera-surveillance. Additionally, this study provides some valuable insights into the influence of camera presence on behavior in general

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV