α-Mangostin Effectively Inhibits Chikungunya Virus Replication in HepG2 Cells

Chikungunya virus (CHIKV) is an arthropod-transmitted Alphavirus endemic to countries in Africa and Asia, including Indonesia, which causes debilitating arthralgia which can last several years. The rapid spread of CHIKV to new areas makes the discovery of antiviral agents a high priority. α-mangostin is a xanthone from mangosteen (Garcinia mangostana) pericarp and has antiviral activity against Hepatitis C and Dengue viruses. We investigated the antiviral activity of α-mangostin against CHIKV in HepG2 cells in pre-, post- and combination treatments compared to the common antiviral medicine ribavirin, as well their cytotoxicity. Our results show dose-responsive reductions in viral titer in all treatment regimes, with post- and combination treatments being more effective than pre-treatment only (IC50 = 7.79, 5.99 and 6.39 µM, respectively), but with poor specificity (SI = 1.39, 1.81 and 1.70, respectively) compared to ribavirin. Neither compound showed a direct virucidal effect. These results suggest α-mangostin effectively inhibits CHIKV replication in this cell line

Comparing Manuka and other medical honeys as adjunct to antibiotic therapy against facultative anaerobes

Lorna Fyfe - ORCiD: 0000-0002-4490-1834 https://orcid.org/0000-0002-4490-1834The development of antibiotic resistance in pathogenic bacteria has created a push for new treatments, with honeys (especially Manuka) becoming a common focus due to their strong antimicrobial action. However, alternatives to Manuka are necessary, as its production is vulnerable. Additionally, research is lacking on how honey affect facultative anaerobic bacteria grown in anaerobic conditions and how honey and antibiotics interact in these conditions. In order to understand these interactions and find novel honey candidates, we investigated the antibacterial effects of four honeys (two Manuka, one Chilean and one ‘Santa Cruz’ honeydew honey) against Staphylococcus aureus and Pseudomonas aeruginosa grown aerobically and anaerobically in broth cultures, and how the honeys affected the action of common antibiotics against these bacteria using agar diffusion assays. We found all honeys to be highly effective at 75% honey, with no significant differences between honeys, showing that other honeys were suitable alternatives to Manuka at such high concentrations. At 20%, oxygen availability and bacterial species impacted the effectiveness of honeys as Santa Cruz honey was most effective aerobically but failed anaerobically, while Manuka honeys were effective against S. aureus but not P. aeruginosa in both conditions, and Chilean honey was ineffective against all samples. The addition of honey increased bacterial sensitivity to antibiotics in some cases, varying with aerobic conditions. The antibacterial activity of the honeys, and differences in conditions whether aerobically or anaerobically, were not correlated with pH, antioxidant capacity or total phenolic count. Since in all cases honeys were either beneficial or of no effect, these results supported the use of honey as adjunct to antibiotic therapy in scenarios such as on bandages, with honeys other than Manuka also being worth consideration.http://doi.org/10.17576/jsm-2022-5105-0551pub

Comparing Manuka and other medical honeys as adjunct to antibiotic therapy against facultative anaerobes

The development of antibiotic resistance in pathogenic bacteria has created a push for new treatments, with honeys (especially Manuka) becoming a common focus due to their strong antimicrobial action. However, alternatives to Manuka are necessary, as its production is vulnerable. Additionally, research is lacking on how honey affect facultative anaerobic bacteria grown in anaerobic conditions and how honey and antibiotics interact in these conditions. In order to understand these interactions and find novel honey candidates, we investigated the antibacterial effects of four honeys (two Manuka, one Chilean and one ‘Santa Cruz’ honeydew honey) against Staphylococcus aureus and Pseudomonas aeruginosa grown aerobically and anaerobically in broth cultures, and how the honeys affected the action of common antibiotics against these bacteria using agar diffusion assays. We found all honeys to be highly effective at 75% honey, with no significant differences between honeys, showing that other honeys were suitable alternatives to Manuka at such high concentrations. At 20%, oxygen availability and bacterial species impacted the effectiveness of honeys as Santa Cruz honey was most effective aerobically but failed anaerobically, while Manuka honeys were effective against S. aureus but not P. aeruginosa in both conditions, and Chilean honey was ineffective against all samples. The addition of honey increased bacterial sensitivity to antibiotics in some cases, varying with aerobic conditions. The antibacterial activity of the honeys, and differences in conditions whether aerobically or anaerobically, were not correlated with pH, antioxidant capacity or total phenolic count. Since in all cases honeys were either beneficial or of no effect, these results supported the use of honey as adjunct to antibiotic therapy in scenarios such as on bandages, with honeys other than Manuka also being worth consideration

Genetic characterization of dengue virus 4 complete genomes from East Java, Indonesia

Dengue is an endemic arboviral disease with continuous transmission in Indonesia for more than five decades. A recent outbreak in Jember, East Java province, demonstrated the predominance of DENV-4, a serotype known for its low global spread and limited transmission. While epidemiological factors such as new serotype introduction and lacking herd immunity may explain its predominance, viral factors may also contribute. Using next-generation sequencing, we generated 13 representative complete genomes of DENV-4 responsible for the outbreak. Phylogenetic and evolutionary analyses on complete genomes were performed to understand the spatial and temporal dynamics of the viruses. Further analyses were done to study amino acid variations in DENV genes, as well as the potential events of recombination and selection pressure within the genomes. We revealed the DENV-4 genetic factors that may lead to its predominance in the 2019 Jember dengue outbreak. A combination of selection pressure and mutational genetic changes may contribute to the DENV-4 predominance in East Java, Indonesia. The possible intra-serotype recombination events involving the non-structural protein 5 (NS5) gene were also observed. Altogether, these genetic factors may act as additional factors behind the complex dengue outbreak mechanism

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Dengue Virus Serotype 4 Is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia

Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1; -2; or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia. Dengue is endemic in the region and outbreaks occur annually. We investigated the clinical characteristics and etiology of dengue-like febrile illness in this regency to understand the disease dynamics. A total of 191 patients with clinical symptoms similar to dengue were recruited during an 11-month study in 2019–2020. Children accounted for the majority of cases and dengue burden was estimated in 41.4% of the cases based on NS1 antigen, viral RNA, and IgG/IgM antibody detection with the majority (73.4%) being primary infections. Secondary infection was significantly associated with a higher risk of severe dengue manifestation. All four DENV serotypes were detected in Jember. Strikingly, we observed the predominance of DENV-4, followed by DENV-3, DENV-1, and DENV-2. Genotype determination using Envelope gene sequence revealed the classification into Genotype I, Cosmopolitan Genotype, Genotype I, and Genotype II for DENV-1, -2, -3, and -4, respectively. The predominance of DENV-4 in Jember may be associated with a new wave of DENV infections and spread in a non-immune population lacking a herd-immunity to this particular serotype

Dengue Virus Serotype 4 Is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia

Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1; -2; or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia. Dengue is endemic in the region and outbreaks occur annually. We investigated the clinical characteristics and etiology of dengue-like febrile illness in this regency to understand the disease dynamics. A total of 191 patients with clinical symptoms similar to dengue were recruited during an 11-month study in 2019–2020. Children accounted for the majority of cases and dengue burden was estimated in 41.4% of the cases based on NS1 antigen, viral RNA, and IgG/IgM antibody detection with the majority (73.4%) being primary infections. Secondary infection was significantly associated with a higher risk of severe dengue manifestation. All four DENV serotypes were detected in Jember. Strikingly, we observed the predominance of DENV-4, followed by DENV-3, DENV-1, and DENV-2. Genotype determination using Envelope gene sequence revealed the classification into Genotype I, Cosmopolitan Genotype, Genotype I, and Genotype II for DENV-1, -2, -3, and -4, respectively. The predominance of DENV-4 in Jember may be associated with a new wave of DENV infections and spread in a non-immune population lacking a herd-immunity to this particular serotype

Design and performance of the multiplexed SQUID/TES array at ninety gigahertz

We present the array performance and astronomical images from early science results from MUSTANG-2, a 90 GHz feedhorn-coupled, microwave SQUID-multiplexed TES bolometer array operating on the Robert C. Byrd Green Bank Telescope (GBT). MUSTANG-2 was installed on the GBT on December 2, 2016 and immediately began commissioning efforts, followed by science observations, which are expected to conclude June 2017. The feedhorn and waveguide-probe-coupled detector technology is a mature technology, which has been used on instrument including the South Pole Telescope, the Atacama Cosmology Telescope, and the Atacama B-mode Search telescope. The microwave SQUID readout system developed for MUSTANG-2 currently reads out 66 detectors with a single coaxial cable and will eventually allow thousands of detectors to be multiplexed. This microwave SQUID multiplexer combines the proven abilities of millimeterwave TES detectors with the multiplexing capabilities of KIDs with no degradation in noise performance of the detectors. Each multiplexing device is read out using warm electronics consisting of a commercially available ROACH board, a DAC/ADC card, and an Intermediate Frequency mixer circuit. The hardware was originally developed by the UC Berkeley Collaboration for Astronomy Signal Processing and Electronic Research (CASPER) group, whose primary goal is to develop scalable FPGA-based hardware with the flexibility to be used in a wide range of radio signal processing applications. MUSTANG-2 is the first on-sky instrument to use microwave SQUID multiplexing and is available as a shared-risk/PI instrument on the GBT. In MUSTANG-2's first season 7 separate proposals were awarded a total of 230 hours of telescope time

High resolution imaging with MUSTANG-2 on the GBT

We present early science results from MUSTANG-2, a 90 GHz feedhorn-coupled, microwave SQUID-multiplexed TES bolometer array operating on the Robert C. Byrd Green Bank Telescope (GBT). The feedhorn and waveguide-probe-coupled detector technology is a mature technology, which has been used on instruments such as the South Pole Telescope, the Atacama Cosmology Telescope, and the Atacama B-mode Search telescope. The microwave SQUID multiplexer-based readout system developed for MUSTANG-2 currently reads out 66 detectors with a single coaxial cable and will eventually allow thousands of detectors to be multiplexed. This microwave SQUID multiplexer combines the proven abilities of millimeter wave TES detectors with the multiplexing capabilities of KIDs with no degradation in noise performance of the detectors. Each multiplexing device is read out using warm electronics consisting of a commercially available ROACH board, a DAC/ADC card, and an Intermediate Frequency mixer circuit. The hardware was originally developed by the Collaboration for Astronomy Signal Processing and Electronic Research (CASPER) group, whose primary goal is to develop scalable FPGA-based hardware with the flexibility to be used in a wide range of radio signal processing applications. MUSTANG-2 is the first on-sky instrument to use microwave SQUID multiplexing and is available as a shared-risk/PI instrument on the GBT. In MUSTANG-2’s first season 7 separate proposals were awarded a total of 230 hours of telescope time