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A cellulose-based aerogel has been synthesized from rambutan peel to mitigate environmental pollution caused by agricultural waste, rendering it an eco-friendly material with potential applications in oil spill remediation as well as enhancing the value of this fruit. The objective of this study was to extract cellulose from rambutan peel using chlorination and alkalization processes, followed by optimizing the synthesis conditions of cellulose-based aerogels from rambutan peel through experimental designs to improve oil removal efficiency. In this research, cellulose-based aerogel material was synthesized using the sol-gel method, utilizing waste from rambutan peel as the substrate and polyvinyl alcohol as the cross-linking agent, followed by freeze-drying. A central composite design with 30 different experimental setups was employed to investigate the influence of cellulose content (1.0–2.0%), cross-linking agent (polyvinyl alcohol) content (0.1–0.3%), ultrasonic time (5–15 min), and ultrasonic power (100–300W) on the oil adsorption capacity (g/g) of cellulose-based aerogels from rambutan peel. The research findings demonstrated successful extraction of cellulose from rambutan peel through chlorination, followed by softening with 17.5% (w/v) sodium hydroxide. Response surface plots indicated that maximizing the cellulose component could lead to a maximum diesel oil adsorption capacity of up to 52.301 g/g. Cellulose-based aerogel exhibits ultra-lightweight properties (0.027±0.002 g/cm3), high porosity (97.88±0.19), hydrophobicity (water contact angle of 152.7°), and superior oil selective adsorption compared to several commercially available materials in the market, demonstrating promising potential for application in treating oil-contaminated water in real-world scenarios.

This research evaluates subchronic toxicities and analgesic effects of Stephania tetrandra S. Moore (S. tetrandra) liquid extract through oral administration in experimental animals. Over 4 weeks of subchronic toxicity research, S. tetrandra was administered to Wistar rats at a dose of 1.6 g/kg body weight (BW) (the dose is equivalent to the expected human dose) and 4.8 g/kg BW (three times the human expected dose), based on World Health Organization (WHO) and Organisation for Economic Co-operation and Development (OECD) recommendations. The analgesic effect was assessed using three models: hot plate, tail-flick, and acetic acid-induced writhing in Swiss mice. Regarding the subchronic toxicity test, after oral administration of S. tetrandra liquid extract, haematological parameters, hepato-renal functions, and microscopic images of the liver and kidney were unchanged compared with the control group. As a result, S. tetrandra liquid extract at both doses of 3.2 g/kg/day and 9.6 g/kg/day tended to reduce pain in the models. The low dose significantly showed peripheral analgesic effects, while the high dose demonstrated better analgesic activity at both central and peripheral sites. In conclusion, S. tetrandra liquid extract did not produce subchronic toxicities in Wistar rats, and has shown experimental analgesic effects.

A Fenton-like catalyst MnO2-Fe3O4/SiO2 is synthesized via a two-step approach. The prepared composite has a mesoporous structure and a high surface area of 190 m2/g. The XRD pattern describes a specific peak of Fe3O4 magnetite on the baseline of amorphous silica. Furthermore, the FTIR spectra not only show the height assigned to stretching vibrations of Si-O-Si bonds, and Fe–O–Fe connections but also exhibit a small peak that matches the Mn–O bonds. SEM images exhibit a porous network structure of the composites with some holes among 30 – 100 nm clusters. The activity of the catalyst is determined in a paracetamol degradation as a Fenton oxidation. The paracetamol removal efficiency is at 85.6% with the optimal condition as initial pH 3, catalyst dosage of 0.15 g/50mL and H2O2 concentration of 1 mL/50 mL. In addition, the catalyst can be reused at least 5 times with a low reduction of the catalytic activity from 85.6% to 80.8%. The experiment results open a direction that has high efficiency in the treatment process of excess paracetamol in pharmacy wastewater.

IntroductionSignal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM.Methods and resultsThis retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence.ConclusionIn our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

Sea-level rise, population growth, and changing land-use patterns will further constrain Florida’s already scarce groundwater and surface water supplies in the coming decades. Significant investments in water supply and water demand management are needed to ensure sufficient water availability for human and natural systems. Section 403.928 (1) (b) of the Florida Statutes requires estimating the expenditures needed to meet the future water demand and avoid the adverse effects of competition for water supplies to 2040. This study considers the 2020–2040 planning period and projects (1) future water demand and supplies; and (2) the total expenditures (capital costs) necessary to meet the future water demand in Florida, USA. The uniqueness of this study compared with the previous studies is the introduction of a probabilistic-based approach to quantify the uncertainty of the investment costs to meet future water demand. We compile data from the U.S. Geological Survey, Florida’s Department of Agriculture & Consumer Services, Florida’s Water Management Districts, and the Florida Department of Environmental Protection to project the future water demand and supplies, and the expenditures needed to meet the demand considering uncertainty in the costs of alternative water supply options. The results show that the total annual water demand is projected to increase by 1405 million cubic meters (+15.9%) by 2040, driven primarily by urbanization. Using the median capital costs of alternative water supply projects, cumulative expenditures for the additional water supplies are estimated between USD 1.11–1.87 billion. However, when uncertainty in the project costs is accounted for, the projected expenditure range shifts to USD 1.65 and USD 3.21 billion. In addition, we illustrate how using Modern Portfolio Theory (MPT) can increase the efficacy of investment planning to develop alternative water supply options. The results indicate that using MPT in selecting the share of each project type in developing water supply options can reduce the standard deviation of capital costs per one unit of capacity by 74% compared to the equal share allocation. This study highlights the need for developing more flexible funding strategies on local, regional, and state levels to finance additional water supply infrastructure, and more cost-effective combinations of demand management strategies and alternative water supply options to meet the water needed for the state in the future.

Background: Infection prevention and control (IPC) competency is critical for healthcare personnel (HCP) and patient safety. In collaboration with the CDC new national IPC training collaborative called Project Firstline, the Oregon Health Authority’s (OHA) Healthcare Associated Infection (HAI) Program established a state-level program in 2021. The goal of Oregon Project Firstline is to provide relevant, accessible, and engaging IPC training materials for our state’s HCP. We assessed the IPC learning needs of Oregon’s healthcare workforce, and to understand the preferred methods and formats of training across the various HCP roles. Methods: OHA’s HAI program recruited HCP by distributing electronic surveys through multiple healthcare, regulatory, and public health partners’ email listservs and HCP-targeted newsletters. Survey responses were recorded from September 23 to December 10, 2021. The HAI program assessed respondents’ IPC knowledge, online and in-person job training preferences, frequently used training devices, and trusted sources for IPC information. An individual’s understanding of an IPC topic was categorized based on their self-assessed confidence in their knowledge and ability to teach the topic to others. In total, 6,382 surveyed responses were analyzed. Results: The average understanding among HCP was lowest in IPC topics relating to triage and isolation of contagious patients and fit testing of respiratory protection devices. For these topics, 3,208 HCP (66.21%) and 3,657 HCP (75.48%) HCP, respectively, did not understand the topic well enough to teach others (Fig. 1). The highest number of HCP (n = 2,512, 39.36%) requested additional training in methods on how to educate others about IPC topics (ie, “train the trainer”). Surveyed respondents most frequently used personal computers for job trainings in both work and at-home settings (n = 4,603, 72.12%) and 3,437 HCP (53.85%) were open to either in-person or remote formats for job education. The CDC and OHA were the most frequented and trusted IPC sources among surveyed HCP: 4,124 HCP (64.62%) and 3,584 HCP (56.16%), respectively. Conclusions: IPC is a critical topic in HCP training across all healthcare facility types and employee roles. Effective educational planning includes understanding the learners’ knowledge needs and preferred methods of learning. Our learning needs assessment identified important IPC knowledge gaps and will help ensure that our training courses will be offered in effective educational formats for Oregon’s diverse HCP. Future training will include appropriate triage of potentially infectious patients, respiratory fit testing, and general IPC “train the trainer” sessions. Additionally, we will offer both in-person and remote options.

There has been an ongoing demand for monitoring landslides due to the heavy economic losses and casualties caused by such natural disasters. In this paper, we introduce a swift landslide detection system that can detect and segment landslides occurring on roads. To tackle the challenges of data collection, we propose an automatic annotation procedure to create a new landslide dataset consisting of 2963 images, termed the LandslidePTIT dataset. Additionally, we construct a novel deep-learning architecture that can perform both classification and segmentation tasks well from a few annotated images of landslides. Specifically, the model consists of four main modules that are delicately designed to solve the few-shot segmentation problem using landslide images, namely hypercorrection construction, attentive squeeze block, a cross-feature layer, and broadcast and squeeze layer. Experimental results exhibit the superiority of the proposed method in comparison with competitive baselines, in terms of both quantitative and qualitative manners.

A patient was diagnosed with Waldenström’s macroglobulinemia (WM) after the initial findings of anemia and ophthalmological findings of retinal hemorrhage. Upon further workup, the patient was found to have an IgM predominant monoclonal gammopathy on serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP). This highlights the need for open communication between different specialties, streamlining rapid and accurate diagnosis. Also highlighted are the unique pathophysiological changes involved in the development of WM. A patient’s primary complaint was blurry vision. After the patient was noted to have a monoclonal gammopathy on SPEP, bone marrow biopsy was performed. The bone marrow biopsy findings were consistent with lymphoplasmacytic lymphoma (LPL). The patient received plasmapheresis and chemotherapy. The disease course is described. The patient saw rapid improvement in all lab abnormalities after the beginning of the appropriate therapy of plasmapheresis and chemotherapy. Remission is common with WM. Regular follow-up with this patient is important.

Summary: Background: The COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on the impact on paediatric influenza-related hospitalisations is limited. We describe influenza-related hospitalisation in children in Canada following the onset of the COVID-19 pandemic. Methods: Data on influenza-related hospitalisations, intensive care unit (ICU) admissions and in-hospital deaths in children across Canada were obtained from the Canadian Immunisation Monitoring Program, ACTive (IMPACT). This national active surveillance initiative comprises 90% of all tertiary care paediatric beds in Canada. The study period included eleven influenza seasons, from the 2010/2011 season until the 2020/2021 season inclusive. Time series modelling was used to compare the observed to predicted influenza-related hospitalisations following the COVID-19 pandemic. Results: Following the COVID-19 pandemic there was a significant decrease in paediatric influenza-related hospitalisations compared to predicted influenza-related hospitalisations for this time period (p

The primary purpose of educational programs is to enhance students' knowledge and skills through pedagogical training activities. However, preschool teachers in Vietnam face limitations in their professional capacity. Thus, this study aimed to address issues by evaluating the level of implementation of pedagogical training activities for preschool education students. The study used a scale for students' pedagogical practice activities to gather quantitative data from 629 participants (managers, lecturers and preschool teachers) in Dong Thap province in Vietnam to assess the extent of implementation of pedagogical training activities for preschool education students. The results showed that preschool teachers may not possess the essential knowledge of pedagogical practices. Pedagogical training uses conventional work-and-activity techniques despite the fact that it prioritizes innovation. Moreover, all school managers, teachers and students recognized the necessity of developing the professional capacity of preschool teachers. These findings illustrate the critical need for revitalizing educational approaches that are consistent with Vietnam's developing preschool teacher professional development context. The present study proposes some measures to innovate pedagogical practice activities in order to meet the requirements for developing the professional capacity of preschool teachers in Vietnam. Such initiatives hold promise for reshaping the educational landscape and fostering a culture of continuous improvement within the primary education sector of Vietnam.

Red Ganoderma lucidum (G. lucidum) is a popular medicinal herb commonly used in Vietnamese traditional remedies due to its potential value for health. In this study, polysaccharides were extracted from G. lucidum using ultrasound-assisted enzymatic extraction method. The response surface methodology and Box–Behnken design were employed to investigate the effects of pH, extraction temperature, extraction time, and ultrasonic power on the content of polysaccharides. Based on ultraviolet-visible spectroscopy analysis, the highest content of polysaccharides in the extract was 32.08 mg/g under optimum experimental parameters including enzyme concentration of 3%, pH of 5.5, extraction temperature of 45°C, extraction time of 30 min, and ultrasonic power of 480 W. The Fourier-transform infrared spectroscopy was also used to identify the functional groups in the extracts. The molecular weights of polysaccharides were determined by gel permeation chromatography. The obtained extract was then evaluated for anticancer activities by using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, showing the anticancer activities with the half-maximal inhibitory concentration value of more than 512 μg/mL. This result suggested that UAEE could be considered as an appropriate and effective extraction method for bioactive crude polysaccharides from G. lucidum.

Project management tools and techniques provide the efficiency and effectiveness in managing and handling the projects. Many tools and techniques have been discovered and applied widely for a long period of time among project managers around the world with great contributions to the success of projects. Vietnam is a developing country and has become an attractive hub for national and international business opportunities. Consequently, there has been an increasing development and expansion of business projects in Vietnam. The purpose of this study is to analyze the use of project management tools and techniques in Vietnam. More specifically, this study aims at investigating: 1) the awareness of business people related to projects, 2) the application of project management tools and techniques within the organization and 3) the challenging obstacles that have prevented organizations in using the tools and techniques. The mixed-method methodology is employed to collect and analyze the data. This study uses interview and questionnaire techniques to collect the data for the study. Several companies in different industries in Vietnam participated in collection of the data. The findings of the study indicate lack of indepth understanding and recognition of project and project management tools and techniques in Vietnamese businesses. The term “project” has not yet become popular in Vietnam. Hence, companies in Vietnam have been facing many obstacles with the application of project management tools and techniques affected on the performance of the projects. The study suggests that the definition and recognition of Project Man-agement should go beyond the current assumption of the Vietnamese business people. Better exercises and practices of the concept of Project Management can benefit the local and international companies. Achieving higher awareness of projects and project management tools can significantly improve economic success of Vietnam.

Accurate and complete immunization data are necessary to assess vaccine coverage, safety and effectiveness. Across Canada, different methods and data sources are used to assess vaccine coverage, but these have not been systematically described. Our primary objective was to examine and describe the methods used to determine immunization coverage in Canada. The secondary objective was to compare routine infant and childhood coverage estimates derived from the Canadian 2013 Childhood National Immunization Coverage Survey (cNICS) with estimates collected from provinces and territories (P/Ts). We collected information from key informants regarding their provincial, territorial or federal methods for assessing immunization coverage. We also collected P/T coverage estimates for select antigens and birth cohorts to determine absolute differences between these and estimates from cNICS. Twenty-six individuals across 16 public health organizations participated between April and August 2015. Coverage surveys are conducted regularly for toddlers in Quebec and in one health authority in British Columbia. Across P/Ts, different methodologies for measuring coverage are used (e.g., valid doses, grace periods). Most P/Ts, except Ontario, measure up-to-date (UTD) coverage and 4 P/Ts also assess on-time coverage. The degree of concordance between P/T and cNICS coverage estimates varied by jurisdiction, antigen and age group. In addition to differences in the data sources and processes used for coverage assessment, there are also differences between Canadian P/Ts in the methods used for calculating immunization coverage. Comparisons between P/T and cNICS estimates leave remaining questions about the proportion of children fully vaccinated in Canada.

The primary aim of Vietnam's new educational program is to enhance students' knowledge and skills through practical learning experiences, enabling them to tackle academic and real-world challenges. However, teachers in Dong Thap province face limitations in their professional competencies. Thus, this study aims to address these issues by examining different models for developing teachers' professional competencies. 1,116 participants participated in this study (258 managers and 868 teachers from high schools and preschools) who completed two questionnaires assessing their professional competence and the perceived importance of professional development. The findings reveal that teachers lack subject knowledge, interdisciplinary understanding and skills in teaching design and assessment. Both school managers and teachers recognize the necessity of professional competence development. A three-step process for enhancing teachers' professional competence is proposed for implementing professional development activities based on these findings.

Recent research across various educational settings has consistently highlighted the statistically positive effects of teachers' efficacy on their level of work engagement. However, an in-depth analysis of the literature reveals an important gap in this study in relation to Vietnamese education. Hence, the present study aims to establish a relationship by investigating the relationship between teachers' efficacy and their work engagement within the framework of the Vietnamese educational system. The study used both the Teachers' Sense of Efficacy Scale (TSES) and the Utrecht Work Engagement Scale (UWES) to gather quantitative data from 354 high school teachers across 6 different high schools. The findings revealed a positive relationship between teachers' efficacy and their work engagement through a combination of factorial analysis and path analysis. These findings are significant because they highlight the value of incorporating self-efficacy concepts into training programs and creating encouraging environments to increase teachers' levels of engagement with their jobs. It is essential to prioritize the use of random sampling techniques in future research initiatives in order to generate a sample that is more extensive and applicable to a broader range of situations. Future researchers may explore incorporating qualitative research methodologies to better understand the impact of teacher efficacy by capturing the unique narratives and perspectives of teachers. This approach would provide a complete understanding of the dynamic relationship between teacher efficacy and work engagement.

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.

Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6-59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010-11 to 2013-14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24-59 months, 48% (95%CI, 12%-69%) for children aged 6-23 months, 77% (95%CI, 47%-90%) for 2010-11, 59% (95%CI, 13%-81%) for 2011-12, 33% (95%CI, -18% to 62%) for 2012-13, and 72% (95%CI, 42%-86%) for 2013-14. VE in children aged 24-59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012-13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons.

"Vaccine hesitancy" is a concept now frequently used in vaccination discourse. The increased popularity of this concept in both academic and public health circles is challenging previously held perspectives that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. A consultation study was designed to assess the opinions of experts and health professionals concerning the definition, scope, and causes of vaccine hesitancy in Canada. We sent online surveys to two panels (1- vaccination experts and 2- front-line vaccine providers). Two questionnaires were completed by each panel, with data from the first questionnaire informing the development of questions for the second. Our participants defined vaccine hesitancy as an attitude (doubts, concerns) as well as a behaviour (refusing some / many vaccines, delaying vaccination). Our findings also indicate that both vaccine experts and front-line vaccine providers have the perception that vaccine rates have been declining and consider vaccine hesitancy an important issue to address in Canada. Diffusion of negative information online and lack of knowledge about vaccines were identified as the key causes of vaccine hesitancy by the participants. A common understanding of vaccine hesitancy among researchers, public health experts, policymakers and health care providers will better guide interventions that can more effectively address vaccine hesitancy within Canada.

Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections.We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses.Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) -0.20 days, 95% CI -0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p

BACKGROUND: Little is known about risk factors for severe outcomes in patients infected with H5N1 and no systematic review has been conducted. Understanding risk factors is an important step for prioritizing prophylaxis or treatment in the event of a pandemic. OBJECTIVES: To systematically evaluate risk factors for severe outcomes in patients with avian influenza H5N1 infection. DATA SOURCES: MEDLINE, EMBASE, CINAHL, GlobalHealth, and CENTRAL through March 2011. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies of any design published in English, French, Spanish, German or Korean that reported on risk factor-outcome combinations of interest in participants with confirmed H5N1 infections. Outcomes considered included death, ventilator support, hospital and ICU admission, pneumonia, and composite outcomes. STUDY APPRAISAL: Risk of bias was assessed using the Newcastle-Ottawa scale (NOS). RESULTS: We identified 20 studies reporting on 999 patients infected with H5N1. The majority of studies (n = 14, 70%) were at intermediate risk of bias, i.e. 4-6 points on the NOS. Females were at increased risk of death (OR 1.75, 95% CI 1.27-2.44), while young age, in particular

Theta-defensins (θ-defensins) are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1-5 (RTDs 1-5). RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1-5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1-5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.

Defensins are antimicrobial peptides expressed by plants and animals. In mammals there are three subfamilies of defensins, distinguished by structural features: alpha, beta and theta. Alpha and beta-defensins are linear peptides with broad anti-microbial activity that are expressed by many mammals including humans. In contrast, theta-defensins are cyclic anti-microbial peptides made by several non-human primates but not humans. All three defensin types have anti-HIV-1 activity, but their mechanisms of action differ. We studied the anti-HIV-1 activity of one defensin from each group, HNP-1 (alpha), HBD-2 (beta) and RTD-1 (theta). We examined how each defensin affected HIV-1 infection and demonstrated that the cyclic defensin RTD-1 inhibited HIV-1 entry, while acyclic HNP-1 and HBD-2 inhibited HIV-1 replication even when added 12 hours post-infection and blocked viral replication after HIV-1 cDNA formation. We further found that all three defensins downmodulated CXCR4. Moreover, RTD-1 inactivated X4 HIV-1, while HNP-1 and HBD-2 inactivated both X4 and R5 HIV-1. The data presented here show that acyclic and cyclic defensins block HIV-1 replication by shared and diverse mechanisms. Moreover, we found that HNP-1 and RTD-1 directly inhibited firefly luciferase enzymatic activity, which may affect the interpretation of previously published data.