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In the absence of an active prophylactic vaccine against HIV-1, passively administered, broadly neutralizing antibodies (bnAbs) identified in some chronically infected persons were shown to prevent HIV-1 infection in animal models. However, passive administration of bnAbs may not be suited to prevent sexual HIV-1 transmission in high-risk cohorts, as a continuous high level of active bnAbs may be difficult to achieve at the primary site of sexual transmission, the human vagina with its acidic pH. Therefore, we used Lactobacillus, a natural commensal in the healthy vaginal microbiome, to express bn nanobodies (VHH) against HIV-1 that we reported previously. After demonstrating that recombinant VHHA6 expressed in E. coli was able to protect humanized mice from mucosal infection by HIV-1Bal, we expressed VHHA6 in a soluble or in a cell-wall-anchored form in Lactobacillus rhamnosus DSM14870. This strain is already clinically applied for treatment of bacterial vaginosis. Both forms of VHHA6 neutralized a set of primary epidemiologically relevant HIV-1 strains in vitro. Furthermore, VHHA6 was still active at an acidic pH. Thus, lactobacilli expressing bn VHH potentially represent an attractive vector for the passive immunization of women in cohorts at high risk of HIV-1 transmission.The COVID-19 pandemic has impacted a wide range of health services. This study aimed to quantify the impact of the COVID-19 pandemic on manual therapy service utilization within the Australian private healthcare setting during the first half of 2020. Quarterly data regarding the number and total cost of services provided were extracted for each manual therapy profession (i.e., chiropractic, osteopathy, and physiotherapy) for the period January 2015 to June 2020 from the Australian Prudential Regulation Authority. Time series forecasting methods were used to estimate absolute and relative differences between the forecasted and observed values of service utilization. An estimated 1.3 million (13.2%) fewer manual therapy services, with a total cost of AUD 84 million, were provided within the Australian private healthcare setting during the first half of 2020. Reduction in service utilization was considerably larger in the second quarter (21.7%) than in the first quarter (5.7%), and was larger in physiotherapy (20.6%) and osteopathy (12.7%) than in chiropractic (5.2%). The impact varied across states and territories, with the largest reductions in service utilization observed in New South Wales (17.5%), Australian Capital Territory (16.3%), and Victoria (16.2%). The COVID-19 pandemic has had a profound impact on manual therapy service utilization in Australia. The magnitude of the decline in service utilization varied considerably across professions and locations. The long-term consequences of this decline in manual therapy utilization remain to be determined.Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the UL29 essential gene of HSV-1 have demonstrated high efficacy against HSV-1 in vitro and in vivo. Here, we assessed the antiviral potential of a UL29 siRNA swarm against circulating strains of HSV-1, in comparison with acyclovir. All circulating strains were sensitive to both antivirals, with the half-maximal inhibitory concentrations (IC50) in the range of 350-1911 nM for acyclovir and 0.5-3 nM for the UL29 siRNA swarm. Additionally, we showed that an acyclovir-resistant HSV-1, devoid of thymidine kinase, is highly sensitive to UL29 siRNA treatment (IC50 1.0 nM; Imax 97%). Moreover, the detected minor variations in the RNAi target of the HSV strains had no effect on the potency or efficacy of UL29 siRNA swarm treatment. Our findings support the development of siRNA swarms for the treatment of HSV-1 infections, in order to circumvent any potential acyclovir resistance.Cyber situational awareness has been proven to be of value in forming a comprehensive understanding of threats and vulnerabilities within organisations, as the degree of exposure is governed by the prevailing levels of cyber-hygiene and established processes. A more accurate assessment of the security provision informs on the most vulnerable environments that necessitate more diligent management. [https://www.selleckchem.com/products/epz-5676.html find more] The rapid proliferation in the automation of cyber-attacks is reducing the gap between information and operational technologies and the need to review the current levels of robustness against new sophisticated cyber-attacks, trends, technologies and mitigation countermeasures has become pressing. A deeper characterisation is also the basis with which to predict future vulnerabilities in turn guiding the most appropriate deployment technologies. Thus, refreshing established practices and the scope of the training to support the decision making of users and operators. The foundation of the training provision is the use of Cyber-Ranges (CRs) and Test-Beds (TBs), platforms/tools that help inculcate a deeper understanding of the evolution of an attack and the methodology to deploy the most impactful countermeasures to arrest breaches. In this paper, an evaluation of documented CR and TB platforms is evaluated. CRs and TBs are segmented by type, technology, threat scenarios, applications and the scope of attainable training. To enrich the analysis of documented CR and TB research and cap the study, a taxonomy is developed to provide a broader comprehension of the future of CRs and TBs. The taxonomy elaborates on the CRs/TBs dimensions, as well as, highlighting a diminishing differentiation between application areas.The mucolipin-1 (TRPML1) channel maintains lysosomal ionic homeostasis and regulates autophagic flux. Defects of TRPML1 lead to lysosomal storage diseases and neurodegeneration. In this report, we discuss emerging evidence pertaining to differential regulation of TRPML1 signaling pathways in cancer progression with the goal of leveraging the oncogenic potential of TRPML1 to inspire therapeutic interventions.