Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection

Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH

Are we tackle ready? Cross-sectional video analysis of match tackle characteristics in elite women's Rugby Union

The tackle contest is the most common and most injurious match contact event in rugby and is an indicator of performance. Tackle Ready is World Rugby's tackle technique education program. Limited research has characterized the tackle contest in women's rugby. The purpose of this study is to: (1) identify the match situational characteristics, ball-carrier and tackler technical actions demonstrated in elite women's Rugby Union and (2) to determine the extent to which Tackle Ready recommended tackle techniques were exhibited. Technical characteristics for 1500 tackle events in the 2022–2023 Women's Six Nations Championship were visually assessed according to a predefined coding framework and the Tackle Ready program. Tackles lacked full completion (0.2%) of the 22 coded Tackle Ready techniques with 47% of the recommended techniques demonstrated in each tackle on average (range 15%–98%). A high proportion of tackles involved two defenders (48%), approaching ball-carriers from the side (38%) or oblique angles (39%), in an upright position (30%), and with initial contact made with the arm (51%). Incorrect pre-contact head positioning and head placement upon contact accounted for 50% and 15% of tackles, respectively, and there was a mean of 14 (95% CI 11–18) head and neck contacts to a tackler and 18 (95% CI 14–22) head and neck contacts to a ball-carrier per game. Targeted interventions to encourage adoption of recommended techniques are needed to reduce tackle-related injury risk in women's rugby. This study provides valuable context for future discussion across law enforcement, coach education and gender-specific tackle coaching in the women's game.Irish Research Council. Open access funding provided by IReL.https://onlinelibrary.wiley.com/journal/15367290hj2024Sports MedicineSDG-03:Good heatlh and well-bein

Whole-body diffusion-weighted imaging for staging malignant lymphoma in children

CT is currently the mainstay in staging malignant lymphoma in children, but the risk of second neoplasms due to ionizing radiation associated with CT is not negligible. Whole-body MRI techniques and whole-body diffusion-weighted imaging (DWI) in particular, may be a good radiation-free alternative to CT. DWI is characterized by high sensitivity for the detection of lesions and allows quantitative assessment of diffusion that may aid in the evaluation of malignant lymphomas. This article will review whole-body MRI techniques for staging malignant lymphoma with emphasis on whole-body DWI. Furthermore, future considerations and challenges in whole-body DWI will be discussed

Immunomodulatory Effects of Non-Thermal Plasma in a Model for Latent HIV-1 Infection: Implications for an HIV-1-Specific Immunotherapy

In people living with HIV-1 (PLWH), antiretroviral therapy (ART) eventually becomes necessary to suppress the emergence of human immunodeficiency virus type 1 (HIV-1) replication from latent reservoirs because HIV-1-specific immune responses in PLWH are suboptimal. Immunotherapies that enhance anti-HIV-1 immune responses for better control of virus reemergence from latent reservoirs are postulated to offer ART-free control of HIV-1. Toward the goal of developing an HIV-1-specific immunotherapy based on non-thermal plasma (NTP), the early immunological responses to NTP-exposed latently infected T lymphocytes were examined. Application of NTP to the J-Lat T-lymphocyte cell line (clones 10.6 and 15.4) stimulated monocyte recruitment and macrophage maturation, which are key steps in initiation of an immune response. In contrast, CD8+ T lymphocytes in a mixed lymphocyte reaction assay were not stimulated by the presence of NTP-exposed J-Lat cells. Furthermore, co-culture of NTP-exposed J-Lat cells with mature phagocytes did not modulate their antigen presentation to primary CD8+ T lymphocytes (cross-presentation). However, reactivation from latency was stimulated in a clone-specific manner by NTP. Overall, these studies, which demonstrated that ex vivo application of NTP to latently infected lymphocytes can stimulate key immune cell responses, advance the development of an NTP-based immunotherapy that will provide ART-free control of HIV-1 reactivation in PLWH

Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection.

Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH

Antimicrobial stewardship in remote primary healthcare across northern Australia

Background: The high burden of infectious disease and associated antimicrobial use likely contribute to the emergence of antimicrobial resistance in remote Australian Aboriginal communities. We aimed to develop and apply context-specific tools to audit antimicrobial use in the remote primary healthcare setting.Methods: We adapted the General Practice version of the National Antimicrobial Prescribing Survey (GP NAPS) tool to audit antimicrobial use over 2-3 weeks in 15 remote primary healthcare clinics across the Kimberley region of Western Australia (03/2018-06/2018), Top End of the Northern Territory (08/2017-09/2017) and far north Queensland (05/2018-06/2018). At each clinic we reviewed consecutive clinic presentations until 30 presentations where antimicrobials had been used were included in the audit. Data recorded included the antimicrobials used, indications and treating health professional. We assessed the appropriateness of antimicrobial use and functionality of the tool.Results: We audited the use of 668 antimicrobials. Skin and soft tissue infections were the dominant treatment indications (WA: 35%; NT: 29%; QLD: 40%). Compared with other settings in Australia, narrow spectrum antimicrobials like benzathine benzylpenicillin were commonly given and the appropriateness of use was high (WA: 91%; NT: 82%; QLD: 65%). While the audit was informative, non-integration with practice software made the process manually intensive.Conclusions: Patterns of antimicrobial use in remote primary care are different from other settings in Australia. The adapted GP NAPS tool functioned well in this pilot study and has the potential for integration into clinical care. Regular stewardship audits would be facilitated by improved data extraction systems

Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats

Environmental enrichment (EE) exerts beneficial effects on brain plasticity, cognition, and anxiety/depression, leading to a brain that can counteract deficits underlying various brain disorders. Because the complexity of the EE commonly used makes it difficult to identify causal aspects, we examined possible factors using a 2 X 2 design with social EE (two vs. six rats) and physical EE (physically enriched vs. nonenriched). For the first time, we demonstrate that social and physical EE have differential effects on brain plasticity, cognition,and ultrasonic communication. Expectedly, physical EE promoted neurogenesis in the dentate gyrus of the hippocampal formation, but not in the subventricular zone, and, as a novel finding, affected microRNA expression levels, with the activity-dependent miR-124 and miR-132 being upregulated. Concomitant improvements in cognition were observed, yet social deficits were seen in the emission of prosocial 50-kHz ultrasonic vocalizations (USV) paralleled by a lack of social approach in response to them, consistent with the intense world syndrome/theory of autism. In contrast, social EE had only minor effects on brain plasticity and cognition, but led to increased prosocial 50-kHz USV emission rates and enhanced social approach behavior. Importantly, social deficits following physical EE were prevented by additional social EE. The finding that social EE has positive whereas physical EE has negative effects on social behavior indicates that preclinical studies focusing on EE as a potential treatment in models for neuropsychiatric isorders haracterized by social deficits, such as autism, should include social EE in ddition to hysical EE, because its lack might worsen social deficits.J. Comp. Neurol. 524:1586–1607, 2016.The Deutsche Forschungsgemeinschaft/[HO2402/6‐1]/DFG/GermanyThe Deutsche Forschungsgemeinschaft/[SCHR1136/3‐1]/DFG/GermanyThe Deutsche Forschungsgemeinschaft/[SCHW559/10‐1]/DFG/GermanyThe Deutsche Forschungsgemeinschaft/[WO1732/4‐1]/DFG/GermanyUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Psicológicas (IIP)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN