Regulating greenhouse gas dynamics in tidal wetlands: Impacts of salinity gradients and water pollution.

Tidal wetlands play a critical role in emitting greenhouse gases (GHGs) into the atmosphere; our understanding of the intricate interplay between natural processes and human activities shaping their biogeochemistry and GHG emissions remains lacking. In this study, we delve into the spatiotemporal dynamics and key drivers of the GHG emissions from five tidal wetlands in the Scheldt Estuary by focusing on the interactive impacts of salinity and water pollution, two factors exhibiting contrasting gradients in this estuarine system: pollution escalates as salinity declines. Our findings reveal a marked escalation in GHG emissions when moving upstream, primarily attributed to increased concentrations of organic matter and nutrients, coupled with reduced levels of dissolved oxygen and pH. These low water quality conditions not only promote methanogenesis and denitrification to produce CH4 and N2O, respectively, but also shift the carbonate equilibria towards releasing more CO2. As a result, the most upstream freshwater wetland was the largest GHG emitter with a global warming potential around 35 to 70 times higher than the other wetlands. When moving seaward along a gradient of decreasing urbanization and increasing salinity, wetlands become less polluted and are characterized by lower concentrations of NO3-, TN and TOC, which induces stronger negative impact of elevated salinity on the GHG emissions from the saline wetlands. Consequently, these meso-to polyhaline wetlands released considerably smaller amounts of GHGs. These findings emphasize the importance of integrating management strategies, such as wetland restoration and pollution prevention, that address both natural salinity gradients and human-induced water pollution to effectively mitigate GHG emissions from tidal wetlands.

Sex-specific associations between air pollutants and asthma prevalence in Japanese adults: a population-based study.

This study investigated the association between air pollutants and asthma prevalence in male and female Japanese adults. In this retrospective cross-sectional analysis, annual mean exposure levels of air pollutants, specifically nitrogen dioxide (NO2) and particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5), were assessed at a local monitoring site. Multivariable logistic regression models, adjusted for genetic and/or lifestyle factors, were used to explore the association between air pollutants and asthma, with stratification by sex. A total of 1,497 participants aged ≥40 years were included. Their mean age was 65.9 ± 12.4 years, with 847 being women. Overall, 91 participants were diagnosed with asthma. In the multivariable model, ambient exposure levels of NO2 and PM2.5 were significantly associated with asthma in women but not in men. This study highlights sex as a significant determinant of the link between air pollutants and asthma exacerbation, particularly among female Japanese adults.

Longitudinal relationship between screen-based sedentary behavior and nutrient intake in Japanese children: an observational epidemiological cohort study.

BACKGROUND: Concerns regarding the impact of screen-based sedentary behavior on health have been increasing. Therefore, the present study investigated the longitudinal relationship between multiple screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted utilizing 3 years longitudinal data. Study subjects were 740 Japanese children aged between 6 and 12 years at baseline and between 9 and 15 years in the follow-up. Screen-based sedentary behavior was assessed using screen time, including television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use. The main outcomes were the intakes of nutrients. Mixed effect multivariate linear regression analyses were used to examine the longitudinal relationship between screen-based sedentary time and nutrient intake. Covariates included in the multivariable analysis consisted of sex, age, solitary eating, skipping breakfast, staying up late, and body weight status, as confounders, and physical inactivity, as mediator. RESULTS: In boys, a longer total screen time longitudinally correlated with higher intake of energy and lower intakes of protein, dietary fiber, minerals, and vitamins. In girls, longer total screen time longitudinally associated with higher intake of sucrose and lower intakes of protein, minerals, and vitamins. In boys, a longer TV viewing time was associated with higher intake of sucrose and lower intakes of protein, minerals, and vitamins. In girls, a longer TV viewing time was associated with higher intake of carbohydrates and lower intakes of protein, fat, minerals, and vitamins. In boys, relationships were observed between a longer PC use time and higher intakes of energy as well as lower intakes of protein, minerals, and vitamins. Relationship was observed between longer PC use time and lower intakes of minerals in girls. An increased MP use time was associated with higher intakes of energy, and lower intakes of protein, sucrose, dietary fiber, minerals, and vitamins in boys. A longer MP use time was associated with higher intakes of fat, and salt as well as lower intakes of carbohydrates, protein, minerals, and vitamins in girls. CONCLUSIONS: The present results revealed that longer screen-based sedentary behaviors were longitudinally associated with nutrient intake in children and adolescents. Future study is needed to elucidate these relationships.

The impact of air pollution on neurocognitive development: Adverse effects and health disparities.

Air pollution is recognized as a major public health concern. The number of deaths related to ambient air pollution has increased in recent years and is projected to continue rising. Additionally, both short- and long-term air pollution exposure has been linked with deleterious effects on neurocognitive function and development. While air pollution poses as a threat to everyone, people of color and individuals of lower socioeconomic status are often exposed to elevated levels of air pollution as a function of systemic racism and classism. Further, given additional disparities in access to healthcare and other compounding stressors, adverse effects of air pollution on neurocognitive health are exacerbated among individuals who hold marginalized identities-making effects both less likely to be detected and treated. This review examines evidence of the effects of air pollution on neurocognitive development across the lifespan and incorporates an environmental justice perspective to highlight disparities in air pollution exposure across race and socioeconomic status. Last, upon the reviewed evidence, limitations of past research and recommendations for policy are discussed.

A retrospective cohort study on the association between poor sleep quality in junior high school students and high hemoglobin A1c level in early adults with higher body mass index values.

BACKGROUND: Few epidemiological studies have been performed to clarify the association between glucose metabolism disorders in early adults (20 years old) and physiological and environmental factors, including body mass index (BMI) in junior high school days. Therefore, we examined the association between hemoglobin A1c (HbA1c) level and body size (BMI) in early adulthood and lifestyles, including sleep habits and BMI in junior high school days in Shika town, a small town in Japan, by conducting a retrospective cohort study. METHODS: We examined the HbA1c levels and body size (BMI) of 99 early adults who turned 20 years old between 2016 and 2020 and were residing in Shika town, Ishikawa Prefecture. We obtained the information on lifestyles and living environment factors, including BMI, from a questionnaire survey conducted among the subjects during their junior high school days (13-15 years old) from 2009 to 2013. RESULTS: No correlations were observed between the HbA1c levels and the BMI values of the early adults. A two-way analysis of covariance (with the HbA1c levels and BMI values of the early adults as main factors) of the body size and lifestyle habits of the junior high school students revealed that "sleep quality in junior high school" was significantly poorer in the high HbA1c group than in the low HbA1c group in the early adults with high BMI values only. This result was also supported by the logistic regression analysis result. CONCLUSIONS: The present results indicate that poor sleep quality in junior high school was associated with the high HbA1c levels of the early adults with higher BMI values, which suggests that good sleep quality in junior high school prevents the development of hyperglycemia. However, the present study did not find any relationship between early-adult BMI and HbA1c level.

Syntheses and studies of deuterated Imdiazo[1,2-a]pyridine-3-carboxamides with potent anti-tuberculosis activity and improved metabolic properties.

The imidazo[1,2-a]pyridine-3-carboxyamides (IAPs) are a unique class of compounds endowed with impressive nanomolar in vitro potency against Mycobacterium tuberculosis (Mtb) as exemplified by clinical candidate Telacebec (Q203). These compounds target mycobacterial respiration through inhibition of the QcrB subunit of cytochrome bc1:aa3 super complex resulting in bacteriostatic efficacy in vivo. Our labs have had a long-standing interest in the design and development of IAPs. However, some of these compounds suffer from short in vivo half-lives, requiring multiple daily dosing or the addition of a cytochrome P450 inhibitor for murine efficacy evaluations. Deuteration has been shown to decrease metabolism as the C-D bond is stronger than the CH bond. Herein we describe our efforts on design and synthesis of potent deuterated IAPs and the effect that deuteration has upon metabolism through microsomal stability studies.

Australindolones, New Aminopyrimidine Substituted Indolone Alkaloids from an Antarctic Tunicate Synoicum sp.

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the invertebrates obtained during the cruise were screened in a zebrafish-based phenotypic assay. The Synoicum sp. extract induced embryonic dysmorphology characterized by axis truncation, leading to the isolation of aminopyrimidine substituted indolone (1-4) and indole (5-12) alkaloids. While the primary bioactivity tracked with previously reported meridianins A-G (5-11), further investigation resulted in the isolation and characterization of australindolones A-D (1-4) and the previously unreported meridianin H (12).

A new role for Notch in the control of polarity and asymmetric cell division of developing T cells.

A fundamental question in biology is how single cells can reliably produce progeny of different cell types. Notch signalling frequently facilitates fate determination. Asymmetric cell division (ACD) often controls segregation of Notch signalling by imposing unequal inheritance of regulators of Notch. Here, we assessed the functional relationship between Notch and ACD in mouse T cell development. To attain immunological specificity, developing T cells must pass through a pivotal stage termed ß-selection, which involves Notch signalling and ACD. We assessed functional interactions between Notch1 and ACD during ß-selection through direct presentation of Notch ligands, DL1 and DL4, and pharmacological inhibition of Notch signalling. Contrary to prevailing models, we demonstrate that Notch signalling controls the distribution of Notch1 itself and cell fate determinants, α-adaptin and Numb. Furthermore, Notch and CXCR4 signalling cooperated to drive polarity during division. Thus, Notch signalling directly orchestrates ACD, and Notch1 is differentially inherited by sibling cells.This article has an associated First Person interview with the first author of the paper.

Possible high-grade squamous intraepithelial lesion (pHSIL) in the new cervical screening paradigm: The outcomes and the role of clinicopathological review.

BACKGROUND: A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL). AIMS: This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions. MATERIALS AND METHODS: Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included. MAIN OUTCOME MEASURES: The primary outcome of the study was histological confirmation of HSIL. RESULTS: Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia. CONCLUSIONS: Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.

Effect of increasing levels of rice distillers' by-product on growth performance, nutrient digestibility, blood profile and colonic microbiota of weaned piglets.

OBJECTIVE: This study was conducted to evaluate the effects of diets containing different wet rice distillers' by-product (RDP) levels on growth performance, nutrient digestibility, blood profiles and gut microbiome of weaned piglets. METHODS: A total of 48 weaned castrated male crossbred pigs, initial body weight 7.54±0.97 kg, and age about 4 wks, were used in this experiment. The piglets were randomly allocated into three iso-nitrogenous diet groups that were fed either a control diet, a diet with 15% RDP, or a diet with 30% RDP for a total of 35 days. Chromium oxide was used for apparent digestibility measurements. On d 14 and d 35, half of the piglets were randomly selected for hemato-biochemical and gut microbiota evaluations. RESULTS: Increasing inclusion levels of RDP tended to linearly increase (p≤0.07) average daily gain on d 14 and d 35, and decreased (p = 0.08) feed conversion ratio on d 35. Empty stomach weight increased (p = 0.03) on d 35 while digestibility of diet components decreased. Serum globulin concentration decreased on d 14 (p = 0.003) and red blood cell count tended to decrease (p = 0.06) on d 35, parallel to increase RDP levels. Gene amplicon profiling of 16S rRNA revealed that the colonic microbiota composition of weaned pigs changed by inclusion of RDP over the period. On d 14, decreased proportions of Lachnospiraceae_ge, Ruminococcaceae_ge, Ruminococcaceae_UCG-005, and Bacteroidales_ge, and increased proportions of Prevotellaceae_ge, Prevotella_2, and Prevotella_9 were found with inclusion of RDP, whereas opposite effect was found on d 35. Additionally, the proportion of Lachnospiraceae_ge, Ruminococcaceae_ge, Ruminococcaceae_UCG-005, and Bacteroidales_ge in RDP diets decreased over periods in control diet but increased largely in diet with 30% RDP. CONCLUSION: These results indicate that RDP in a favorable way modulate gastrointestinal microbiota composition and improve piglet performance despite a negative impact on digestibility of lipids and gross energy.

Homoharringtonine stabilizes secondary structure of guanine-rich sequence existing in the 5'-untranslated region of Nrf2.

Homoharringtonine, known as omacetaxine mepesuccinate, is a pharmaceutical drug substance approved for treatment of chronic myeloid leukemia. Here, we report that homoharringtonine (HHT) is a novel chemical inhibitor of NRF2. HHT significantly suppressed NRF2 and ARE-dependent gene expression in human lung carcinoma A549 cells. HHT stabilized secondary structure of guanine-rich sequence existing in the 5'-untranslated region (5'-UTR) of Nrf2 and sensitized A549 cells to etoposide-induced apoptosis. To the best of our knowledge, HHT is the first type of transcriptional inhibitor of Nrf2 that stabilizes guanine-rich sequence existing in the 5'-UTR. Our study also provides a novel mechanism of action underlying how HHT exerts anti-carcinogenic effects in cancer cells.

Effect of the Electrolyte Solvent on Redox Processes in Mg-S Batteries.

Mg-S batteries are attractive for next-generation energy storage because of their high theoretical capacity and low cost. The foremost challenge in Mg-S batteries is designing electrolytes that support reversible electrochemistry at both electrodes. Here, we target a solution-mediated reduction pathway for the S8 cathode by tailoring the electrolyte solvent. Varying the solvent in Mg-based systems is complicated because of the active nature of the solvent in solvating Mg2+ and the complex dynamics of electrolyte-Mg interfaces. To understand the effect of the solvent on the S8 reduction processes in the Mg-S cell, the magnesium-aluminum chloride complex (MACC) electrolyte was prepared in different ethereal solvents. Reversible Mg electrodeposition is demonstrated in the MACC electrolyte in several solvent systems. The electrodeposition overpotentials and current densities are found to vary with the solvent, suggesting that the solvent plays a noninnocent role in the electrochemical processes at the Mg interface. Mg-S cells are prepared with the electrolytes to understand how the solvent affects the reduction of S8. A reductive wave is present in all linear-sweep voltammograms, and the peak potential varies with the solvent. The peak potential is approximately 0.8 V versus Mg/Mg2+, lower than the expected reduction potential of 1.7 V. We rule out passivation of the Mg anode as the cause for the low voltage peak potential, making processes at the S8 cathode the likely culprit. The ability to oxidize MgS with the MACC electrolyte is also examined, and we find that  the oxidation current can be attributed to side reactions at the C-electrolyte interface.

Multimodal method for the scattering by an array of plates connected to an elastic half-space.

An accurate and numerically inexpensive method is presented to calculate the reflection of in-plane waves at the free surface of an elastic substrate supporting a periodic array of plates. The method is based on the expansions of the elastic fields on the pseudo-periodic modes in the substrate and on the Lamb modes in the plates. These expansions involve unknown amplitudes which are determined by simple matrix inversion when accounting for the boundary conditions at the surface of the substrate and at the free edges of the plates. Exemplifying results are reported in a wide range of frequency covering two resonances of the plates which are analyzed: a flexural resonance of slender bodies and the quasi-resonance of the so-called edge mode. The convergence of the method is inspected quantitatively; it is shown that it is good in view of the fact that the stress is singular at the corners of the plates in contact with the substrate. In particular, the scattering coefficients converge as 1/Ns 3/2 with Ns the truncation of the expansions.

In growing pigs, nutritive value and nutrient digestibility of distillers' by-products obtained from two varieties of rice.

In South-East Asia, rice distillers' by-product (RDP) is a widely abundant feedstuff whose adequate incorporation into pig diets is still questionable. Especially, effects of RDP on nutrient digestibility of growing pigs fed corn-soybean meal-based diet are lacking. The objective of this study was to determine nutrient digestibility and energy value of ordinary (ORDP) and glutinous (GRDP) rice distillers' by-product in growing pigs. Two groups of 12 castrated crossbred barrows (Duroc × Landrace × Yorkshire), about 3 months old, 38 ± 1.04-kg initial body weight, were each allocated to a 15-day experiment in which pigs were divided into three isonitrogenous diet-groups. The animals were housed individually in metabolism cages for separated collection of feces and urine. Each diet-group was provided either a control corn-soybean meal diet or a diet in which corn and soybean meal were partly replaced by ORDP or GRDP at 15 or 30% on diet dry matter basis. Glutinous by-product especially showed higher levels in crude protein, neutral/acid detergent fiber, total branched-chain amino acids, and butyric acid. When compared to the control diet, ORDP tented to increase DM intake (P = 0.054) but decreased energy (P < 0.001) and crude protein (P < 0.04) digestibility, while GRDP decreased DM intake (P < 0.001). Both GRDP and ORDP products negatively affected digestibility of ether extract. The average digestible and metabolizable energy of ORDP and GRDP were 17.0 and 16.6, and 17.7, and 17.1 MJ/kg DM, respectively. In conclusion, these results show that both RDP, and especially GRDP, are highly valuable protein and energy sources for pig production.

Aryl Hydrocarbon Receptor Ligands in Cigarette Smoke Induce Production of Interleukin-22 to Promote Pancreatic Fibrosis in Models of Chronic Pancreatitis.

BACKGROUND & AIMS: Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of CP. METHODS: We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4+ T cells. Levels of interleukin-22 (IL22) were measured by enzyme-linked immunosorbent assay and smoking histories were collected. T cells from healthy nonsmokers and smokers were stimulated and incubated with AhR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo[a]pyrene) or antagonists and analyzed by flow cytometry. Mice were given intraperitoneal injections of caerulein or saline, with or without lipopolysaccharide, to induce CP. Some mice were given intraperitoneal injections of AhR agonists at the start of caerulein injection, with or without an antibody against IL22 (anti-IL22) starting 2 weeks after the first caerulein injection, or recombinant mouse IL22 or vehicle (control) intraperitoneally 4 weeks after the first caerulein injection. Mice were exposed to normal air or cigarette smoke for 6 h/d for 7 weeks and expression of AhR gene targets was measured. Pancreata were collected from all mice and analyzed by histology and quantitative reverse transcription polymerase chain reaction. Pancreatic stellate cells and T cells were isolated and studied using immunoblot, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent analyses. RESULTS: Mice given AhR agonists developed more severe pancreatic fibrosis (based on decreased pancreas size, histology, and increased expression of fibrosis-associated genes) than mice not given agonists after caerulein injection. In mice given saline instead of caerulein, AhR ligands did not induce fibrosis. Pancreatic T cells from mice given AhR agonists and caerulein were activated and expressed IL22, but not IL17 or interferon gamma. Human T cells exposed to AhR agonists up-regulated expression of IL22. In mice given anti-IL22, pancreatic fibrosis did not progress, whereas mice given recombinant IL22 had a smaller pancreas and increased fibrosis. Pancreatic stellate cells isolated from mouse and human pancreata expressed the IL22 receptor IL22RA1. Incubation of the pancreatic stellate cells with IL22 induced their expression of the extracellular matrix genes fibronectin 1 and collagen type I α1 chain, but not α2 smooth muscle actin or transforming growth factor-ß. Serum samples from smokers had significantly higher levels of IL22 than those from nonsmokers. CONCLUSIONS: AhR ligands found in cigarette smoke increase the severity of pancreatic fibrosis in mouse models of pancreatitis via up-regulation of IL22. This pathway might be targeted for treatment of CP and serve as a biomarker of disease.

Mycobacterium tuberculosis lineages and anti-tuberculosis drug resistance in reference hospitals across Viet Nam.

BACKGROUND: Mycobacterium tuberculosis, the tuberculosis (TB) pathogen, despite a low level of genetic diversity, has revealed a high variety of biological and epidemiological characteristics linked to their lineages, such as transmissibility, fitness and propensity to acquire drug resistance. This has important implications for the epidemiology of TB. We conducted this first countrywide cross-sectional study to identify the prevalent M. tuberculosis lineages and to assess their epidemiological associations and their relation to drug resistance. The study was conducted among isolates acquired in reference hospitals across Vietnam. Isolates with drug susceptibility testing profiles were identified for their lineages by spoligotyping. Logistic regression was used to investigate the association of M. tuberculosis lineages with location, age and sex of the patients and drug resistance levels. RESULTS: Results showed that the most prevalent lineage was Beijing (55.4 %), followed by EAI (27.5 %), T (6.4 %), LAM (1.3 %), Haarlem (1 %) and Zero type (0.3 %). The proportion of Beijing isolates in the North (70.4 %) and the South (68 %) was higher than in the Centre (28 %) (OR = 1.7 [95 % CI: 1.4-2.0], p < 0.0001), whereas the proportion of EAI isolates in the North (7.1 %) and the South (17 %) was much lower compared with the Centre (59 %) (OR = 0.5 [95 % CI: 0.4-0.6], p < 0.0001). Overall, Beijing isolates were the most likely to be drug-resistant and EAI isolates were the least likely to be drug-resistant, except in the South of Vietnam where EAI is also highly drug-resistant. The proportion of Beijing isolates was significantly higher (p < 0.01), and the proportion of EAI isolates was significantly lower (p < 0.05) in younger patients. The proportion of drug-resistance was higher in isolates collected from male patients and from patients in the middle age groups. CONCLUSIONS: The findings suggest ongoing replacement of EAI lineage, which is mainly more drug-susceptible with highly drug-resistant Beijing lineage in all studied regions of Vietnam. Male patients of working ages should be the focus for better control to prevent the emergence of drug-resistant TB.

TACTICS, an interactive platform for customized high-content bioimaging analysis.

We describe a modular MATLAB® Toolbox named TACTICS for time-lapse image analysis that meets several requirements not generally offered by currently available software packages: (i) the ability to assess quality of extracted imaging information by directly linking data end points to the original position, (ii) massively parallel analysis of each parameter, for flow cytometry-like assessment of possible relationships between parameters within sub-populations of the images, (iii) options for user control of the tracking such as an interface to restrict the analysis region, (iv) manual correction of automated processes and (v) user interfaces for post-tracking analysis that is linked to the original images, including options to view cell pedigrees and normalized polarization ratios based on fluorescence ratiometric measurements.

When Institutions Harm Those Who Depend on Them: A Scoping Review of Institutional Betrayal.

The term institutional betrayal (Smith and Freyd, 2014) builds on the conceptual framework of betrayal trauma theory (see Freyd, 1996) to describe the ways that institutions (e.g., universities, workplaces) fail to take appropriate steps to prevent and/or respond appropriately to interpersonal trauma. A nascent literature has begun to describe individual costs associated with institutional betrayal throughout the United States (U.S.), with implications for public policy and institutional practice. A scoping review was conducted to quantify existing study characteristics and key findings to guide research and practice going forward. Multiple academic databases were searched for keywords (i.e., "institutional betrayal" and "organizational betrayal"). Thirty-seven articles met inclusion criteria (i.e., peer-reviewed empirical studies of institutional betrayal) and were included in analyses. Results identified research approaches, populations and settings, and predictor and outcome variables frequently studied in relation to institutional betrayal. This scoping review describes a strong foundation of published studies and provides recommendations for future research, including longitudinal research with diverse individuals across diverse institutional settings. The growing evidence for action has broad implications for research-informed policy and institutional practice.

Long-acting intramuscular injections of ELQ-331, an antimalarial agent.

The overarching premise of this investigation is that injectable, long-acting antimalarial medication would encourage adherence to a dosage regimen for populations at risk of contracting the disease. To advance support for this goal, we have developed oil-based formulations of ELQ-331 (a prodrug of ELQ-300) that perform as long-acting, injectable chemoprophylactics with drug loading as high as 160 mg/ml of ELQ-331. In a pharmacokinetic study performed with rats, a single intramuscular injection of 12.14 mg/kg maintained higher plasma levels than the previously established minimum fully protective plasma concentration (33.25 ng/ml) of ELQ-300 for more than 4 weeks. The formulations were well tolerated by the rats and the tested dose produced no adverse reactions. We believe that by extending the length of time between subsequent injections, these injectable oil-based solutions of ELQ-331 can offer a more accessible, low-cost option for long-acting disease prevention and reduced transmission in malaria-endemic regions and may also be of use to travelers.

Genetic divergence among members of the Kokobera group of flaviviruses supports their separation into distinct species.

The Kokobera virus group comprises mosquito-borne flaviviruses that cluster together phylogenetically. These viruses are unique to Australia and Papua New Guinea, and have been associated with a mild polyarticular disease in humans. Recent isolation of genetically diverse viruses within this group has prompted analysis of their genetic and phenotypic relationships. Phylogenetic analysis based on complete ORF, the envelope gene or the NS5/3' untranslated region supported the separation of the group into distinct species: Kokobera virus (KOKV), Stratford virus, New Mapoon virus, MK7979 and TS5273. Virulence studies in 3-week-old mice also provided the first evidence that a member of the KOKV group (MK7979) was neuroinvasive after intraperitoneal inoculation. In this context, our recent detection of KOKV group-specific antibodies in horses in the field suggests that these viruses should be considered in the epidemiology of flavivirus encephalitis in Australia.