Human Infections with Plasmodium knowlesi, the Philippines.

Five human cases of infection with the simian malaria parasite Plasmodium knowlesi from Palawan, the Philippines, were confirmed by nested PCR. This study suggests that this zoonotic infection is found across a relatively wide area in Palawan and documents autochthonous cases in the country

Ecosystem restoration and biodiversity conservation for Sustainable Development: a special issue of sustainability

The world is facing unprecedented biodiversity loss due to rampant ecosystem degradation that is further accelerated by climate change. This loss has accelerated the impact of climate change on marginalized and vulnerable societies with consequences for human health, livelihoods, and well-being. The effective implementation of ecological restoration at local, regional and national level can bring diverse benefits not only for the environment but also promote social and economic sustainability to communities. Ecosystem restoration is the supremely important science for the Anthropocene and requires collaboration of experts from diverse disciplines such as social sciences, economics, life sciences, earth and environmental studies, along with policy makers and industrial partners can bring in pragmatic solutions to halt and/or reduce biodiversity loss and protect natural resources from further degradation. This approach is required to address the climate crisis and biodiversity emergency and to achieve the Sustainable Development Goals. It will also contribute to, the Nationally Determined Targets, the Post 2020 global biodiversity targets, focusing on developing a mutually beneficial relationship between people and nature, the UBCCD targets for Land Degradation Neutrality and the success of the UN-Decade on Ecosystem Restoration (2021-2030). It is of paramount importance that integrated, participatory collaborative efforts are made to establish a hybrid knowledge framework that includes scientific, as well indigenous and traditional knowledge, to maximize the success of restoration efforts at local level. This must be effectively integrated in governance instruments and policy planning to enhance institutional capacity to tackle the complex challenges of ecosystem degradation and biodiversity loss and strengthen the global agenda of living in harmony with nature. This special issue invites contributions in the form of original research papers, critical reviews, or opinion articles linking various disciplines, as outlined above, related to the development of integrated sustainable solutions for ecosystem restoration and biodiversity conservation

A simple method to derive speed for the endurance shuttle walk test

Background: The original method for determining endurance shuttle walk test (ESWT) speed involves components that are time consuming for clinicians. We sought to determine: (i) whether components described in the original method for determining ESWT speed held true and; (ii) the agreement between speeds derived using the original method and that equivalent to 85% of the peak speed achieved during the incremental shuttle walk test (ISWT). Methods: Patients with chronic obstructive pulmonary disease (COPD) performed two ISWTs and one ESWT on separate days, wearing a calibrated portable gas analysis unit. A retrospective analysis of these data allowed us to determine whether: (i) the peak rate of oxygen uptake (VO2peak) can be accurately estimated from the incremental shuttle walk distance (ISWD) and; (ii) ESWTs performed at a speed derived using the original method elicited 85% of VO2peak. Agreement between walks speeds was determined using Bland–Altman analysis. Results: Twenty-two participants (FEV1 48 ± 13% predicted, age 66 ± 8 yr) completed the study. The VO2peak estimated from the ISWD was less than that measured during the ISWT (mean difference −4.4; 95% confidence interval (CI), −6.0 to −2.9 ml• kg−1•min−1). The ESWT and ISWT elicited similar VO2peak (mean difference −0.2; 95% CI, −1.5 to 1.2 ml•kg−1•min−1). The mean difference (±limits of agreement) between ESWT speeds was 0.15 (±0.34) km•h−1. Conclusions: Components of the original method for determining the ESWT speed did not hold true in our sample. ESWT speed can be derived by calculating 85% of the peak speed achieved during the ISWT

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

Population genetic analysis of Plasmodium knowlesi reveals differential selection and exchange events between Borneo and Peninsular sub-populations

Funding: A.T. was funded by a Newton Institutional Links Grant (British Council, no. 261868591). S.C. was funded by BloomsburySET and Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1, and MR/X005895/1). T.G.C. was funded by the Medical Research Council UK (Grant nos. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1, and MR/X005895/1).The zoonotic Plasmodium knowlesi parasite is a growing public health concern in Southeast Asia, especially in Malaysia, where elimination of P. falciparum and P. vivax malaria has been the focus of control efforts. Understanding of the genetic diversity of P. knowlesi parasites can provide insights into its evolution, population structure, diagnostics, transmission dynamics, and the emergence of drug resistance. Previous work has revealed that P. knowlesi fall into three main sub-populations distinguished by a combination of geographical location and macaque host (Macaca fascicularis and M. nemestrina). It has been shown that Malaysian Borneo groups display profound heterogeneity with long regions of high or low divergence resulting in mosaic patterns between sub-populations, with some evidence of chromosomal-segment exchanges. However, the genetic structure of non-Borneo sub-populations is less clear. By gathering one of the largest collections of P. knowlesi whole-genome sequencing data, we studied structural genomic changes across sub-populations, with the analysis revealing differences in Borneo clusters linked to mosquito-related stages of the parasite cycle, in contrast to differences in host-related stages for the Peninsular group. Our work identifies new genetic exchange events, including introgressions between Malaysian Peninsular and M. nemestrina-associated clusters on various chromosomes, including in parasite invasion genes (DBPβ, NBPXα and NBPXβ), and important proteins expressed in the vertebrate parasite stages. Recombination events appear to have occurred between the Peninsular and M. fascicularis-associated groups, including in the DBPβ and DBPγ invasion associated genes. Overall, our work finds that genetic exchange events have occurred among the recognised contemporary groups of P. knowlesi parasites during their evolutionary history, leading to apparent mosaicism between these sub-populations. These findings generate new hypotheses relevant to parasite evolutionary biology and P. knowlesi epidemiology, which can inform malaria control approaches to containing the impact of zoonotic malaria on human communities.Publisher PDFPeer reviewe

Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study

OBJECTIVES: Adjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction. DESIGN: Open-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy. SETTING: Six PICUs in Australia and New Zealand. PATIENTS: Children of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021. INTERVENTIONS: Patients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33). MEASUREMENTS AND MAIN RESULTS: Sixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29–120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0–26.0) days in the intervention and 21.0 (0.0–25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5–11.3) days in the intervention group versus 6.9 (3.0–11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6–101.2) hours in the intervention group versus 47.3 (22.4–106.8) hours in the standard care group (median difference –12 hr; 95% CI, –56.8 to 32.7 hr). CONCLUSIONS: In children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT

Accurate Estrogen Receptor Quantification in Patients with Negative and Low-Positive Estrogen-Receptor-Expressing Breast Tumors: Sub-Analyses of Data from Two Clinical Studies

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Population genetic analysis of Plasmodium knowlesi reveals differential selection and exchange events between Borneo and Peninsular sub-populations.

The zoonotic Plasmodium knowlesi parasite is a growing public health concern in Southeast Asia, especially in Malaysia, where elimination of P. falciparum and P. vivax malaria has been the focus of control efforts. Understanding of the genetic diversity of P. knowlesi parasites can provide insights into its evolution, population structure, diagnostics, transmission dynamics, and the emergence of drug resistance. Previous work has revealed that P. knowlesi fall into three main sub-populations distinguished by a combination of geographical location and macaque host (Macaca fascicularis and M. nemestrina). It has been shown that Malaysian Borneo groups display profound heterogeneity with long regions of high or low divergence resulting in mosaic patterns between sub-populations, with some evidence of chromosomal-segment exchanges. However, the genetic structure of non-Borneo sub-populations is less clear. By gathering one of the largest collections of P. knowlesi whole-genome sequencing data, we studied structural genomic changes across sub-populations, with the analysis revealing differences in Borneo clusters linked to mosquito-related stages of the parasite cycle, in contrast to differences in host-related stages for the Peninsular group. Our work identifies new genetic exchange events, including introgressions between Malaysian Peninsular and M. nemestrina-associated clusters on various chromosomes, including in parasite invasion genes (DBP[Formula: see text], NBPX[Formula: see text] and NBPX[Formula: see text]), and important proteins expressed in the vertebrate parasite stages. Recombination events appear to have occurred between the Peninsular and M. fascicularis-associated groups, including in the DBP[Formula: see text] and DBP[Formula: see text] invasion associated genes. Overall, our work finds that genetic exchange events have occurred among the recognised contemporary groups of P. knowlesi parasites during their evolutionary history, leading to apparent mosaicism between these sub-populations. These findings generate new hypotheses relevant to parasite evolutionary biology and P. knowlesi epidemiology, which can inform malaria control approaches to containing the impact of zoonotic malaria on human communities

Prior consumption of a fat meal in healthy adults modulates the brain’s response to fat

Background: Consumption of fat is regulated by reward and homeostatic pathways, but no studies have examined the role of the intake of a high fat meal (HFM) on subsequent brain activation to oral stimuli. Objective: We evaluated how prior consumption of a HFM or water load (WL) modulates reward, homeostatic and taste brain responses to subsequent delivery of oral fat. Methods: A randomized 2-way crossover design (1-week apart) was used to compare prior consumption of a 250mL HFM (520kcal) (rapeseed oil (440kcal), emulsifier, sucrose, flavor cocktail) or non-caloric WL on brain activation to the delivery of repeated trials of an oral flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 male, age=25±2 years, BMI=22.4±0.8kg/m2). Analyses tested differences in brain activation to the CS and FS, and baseline cerebral blood flow (CBF), following the HFM and WL. Individual’s plasma cholecystokinin (CCK) concentration following the HFM was correlated with their BOLD activation. Results: Prior consumption of the HFM compared to the WL led to decreased anterior insula taste activation in response to both the CS (36.3%,P<0.05) and FS (26.5%,P<0.05). The HFM caused reduced amygdala activation (25.1%,P<0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula (5.7%,P<0.01)), homeostatic (hypothalamus (9.2%,P<0.01), thalamus (5.1%,P<0.05))), and reward areas (striatum (9.2%,P<0.01)) following the HFM. Individual’s plasma CCK concentration negatively correlated with brain activation in taste, oral somatosensory and reward areas. Conclusions: To reduce obesity, policy in industry is to lower the fat content of foods. Our results in healthy adults show that a HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain’s response to high fat counterparts, and guide future interventions to reduce obesity