By eliciting inflammatory responses, the human immunosurveillance system notably combats invading pathogens, during which acute phase proteins (CRP and cytokines) are elevated markedly. However, the Pseudomonas aeruginosa is a persistent opportunistic pathogen prevalent at the site of local inflammation, and its acquisition of multiple antibiotic-resistance factors poses grave challenges to patient healthcare management. Using blood samples from infected patients, we demonstrate that P. aeruginosa is effectively killed in the plasma under defined local infection-inflammation condition, where slight acidosis and reduced calcium levels (pH 6.5, 2 mM calcium) typically prevail. We showed that this powerful antimicrobial activity is provoked by crosstalk between two plasma proteins; CRP∶L-ficolin interaction led to communication between the complement classical and lectin pathways from which two amplification events emerged. Assays for C4 deposition, phagocytosis, and protein competition consistently proved the functional significance of the amplification pathways in boosting complement-mediated antimicrobial activity. The infection-inflammation condition induced a 100-fold increase in CRP∶L-ficolin interaction in a pH- and calcium-sensitive manner. We conclude that the infection-induced local inflammatory conditions trigger a strong interaction between CRP∶L-ficolin, eliciting complement-amplification pathways which are autonomous and which co-exist with and reinforce the classical and lectin pathways. Our findings provide new insights into the host immune response to P. aeruginosa infection under pathological conditions and the potential development of new therapeutic strategies against bacterial infection.

Background and Aim Real‐world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real‐world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. Methods We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention‐to‐treat (ITT) and per‐protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. Results A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment‐experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per‐protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. Conclusion The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real‐world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.

Background High levels of sedentary behaviour (SB) are associated with non-communicable diseases. In 2016, the estimated total healthcare expenditure from physical activity (PA) in Thailand added up to $190 million in international dollars. The challenge to reduce SB and increase PA among office workers is more urgent now than ever as Thailand is transforming itself from a predominantly rural country to an increasingly urban one. This study will investigate the effectiveness of a multicomponent short break intervention on the reduction of SB during office hours. Methods/design This two-armed Physical Activity at Work (PAW) cluster randomised controlled trial will recruit 360 office workers from 18 offices in the Thailand’s Ministry of Public Health (MOPH). Offices will be randomised to either the intervention group or the control group. The multicomponent intervention is informed by the Social Ecological Model and Behaviour Change Techniques (BCTs) and contains four components: (i) organisational, including heads of the participating divisions leading exercises, sending encouragement text messages and acknowledging efforts; (ii) social, including team movement breaks and team-based incentives; (iii) environmental, including posters to encourage exercise; and (iv) individual components including real-time PA feedback via an individual device. The main intervention component will be a short break intervention. The primary outcome of this study is the sedentary time of office workers. Secondary outcomes include time spent on PA, cardiometabolic outcomes, work productivity, musculoskeletal pain, and quality of life. The study also includes process and economic evaluations from the individual and societal perspective. Discussion The study will be the first experimental study in Thailand to investigate the effect of a short-break intervention at the workplace on SBs of office workers and health outcomes. The study will also include a cost-effectiveness analysis to inform investments on short break interventions under the Universal Healthcare Coverage in Thailand, which includes health promotion and disease prevention component. Trial registration The PAW study has been registered at the Thai Clinical Trials Registry (TCTR) under the study ID TCTR20200604007 . Registered 02 June 2020,

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