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Animal models for preeclampsia are mostly determined by the experimental induction of hypertension, proteinuria and latterly, endogenous production of anti-angiogenic factors (sFlt-1). The focus on maternal outcome measures is more immediately obvious, with comparative and sequential data of blood pressure and urine protein excretion. In non-human primates, the data concerning birthweight requires a greater number of observations and thus will be accumulated over a longer period of time and a greater number of experimental protocols. The following represents the outcome of over 20 years of experimental preeclampsia (EPE) compared with normal pregnancy outcome data in baboons. MethodsThis data represents the outcomes from 91 pregnancies over the last 25 years at the Australian National Baboon Colony. These pregnancies are attributed to females who had experimental preeclampsia (EPE) and those within the general colony. EPE was induced at day 130 (of 182 days gestation length), and in some protocols, treatments such as inhibitory RNA or placental growth factor (PlGF) were tested. All studies were approved by the institutional Animal Welfare Committee. RESULTS: The overall neonatal birthweight was 697 g ± 115 g. The average birthweight for normal males was 770 ± 105 g; and for male offspring of animals with EPE, 680 ± 113 g; for normal females was 640 ± 95 g and females from EPE pregnancies, 690 ± 43 g. There was only a significant difference in weight for females compared to males overall (p = 0.002), and there was no significant difference in birthweight for males or females subjected to EPE. Correction for treated EPE did not change the outcome. CONCLUSIONS: These data indicate that in a non-human primate model of placental dysfunction through late pregnancy acute ischaemia, there is no measurable effect on baby birthweight compared to normal pregnancy, and no impact from a number of current experimental treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Osteoarthritis (OA) is characterised by synovial joint pain, functional disability and affects ∼13 % of people worldwide, of which ∼16-27 % report Knee-OA (KOA). Glucosamine (Glu) is the most widely used nutraceutical treatment for OA despite a lack of scientific consensus, therefore alternative nutraceutical treatments are required. The aim of this study was to investigate the effect of Lithothamnion species, seawater-derived magnesium and pine bark (Aq + ) on pain, symptoms and improve physical function in symptomatic (sKOA), compared to Glu., Methods: 358 participants were screened. In a double-blinded crossover pilot-trial, sKOA participant (n = 30) were randomly assigned to either the Glu group (2000 mg day -1 ) or Aq + (3056 mg day -1 ) for 12 weeks (clinicaltrials.gov:NCT03106584). The Knee Injury and Osteoarthritis Outcome Score was used to assess subjective pain and symptoms. Timed-up-and-Go (TuG) and Six minute walking distance were used to assess functional change and analgesic use was recorded., Results: Aq + improved pain, with a large effect (P < 0.01, d' = 0.73, 95 %CI 0.201-1.265) and no change for Glu (d' = 0.38, P = 0.06). Only Aq + improved pain (P < 0.05) for males (d' = 0.91, 95 %CI 0.162-1.667) and females (d' = 0.55, 95 %CI 0.210-1.299). In females, Aq + improved TuG by -7.02 % (d' = 0.92, 95 %CI 1.699-0.141) while Glu worsened performance by 4.18 % (P = 0.04). Aq + reduced analgesia by 71.6 %, compared to Glu (P = 0.02; d' = 0.82, 95 %CI 1.524-0.123). Aq + was superior to Glu at improving pain, KOOS subscales, physical function and analgesia use in mild-sKOA. Given these data, Aq + should be considered as a supplementary treatment for early-stage-KOA and may have the potential to reduce use of pain medication, although larger replication studies are required., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The use of a limited set of signatures in nuclear forensics and nuclear safeguards may reduce the discriminating power for identifying unknown nuclear materials, or for verifying processing at existing facilities. Nuclear proliferomics is a proposed new field of study that advocates for the acquisition of large databases of nuclear material properties from a variety of analytical techniques. As demonstrated on a common uranium trioxide polymorph, α-UO 3 , in this paper, nuclear proliferomics increases the ability to improve confidence in identifying the processing history of nuclear materials. Specifically, α-UO 3 was investigated from the calcination of unwashed uranyl peroxide at 350, 400, 450, 500, and 550 °C in air. Scanning electron microscopy (SEM) images were acquired of the surface morphology, and distinct qualitative differences are presented between unwashed and washed uranyl peroxide, as well as the calcination products from the unwashed uranyl peroxide at the investigated temperatures. Differential scanning calorimetry (DSC), UV-Vis spectrophotometry, powder X-ray diffraction (p-XRD), and thermogravimetric analysis-mass spectrometry (TGA-MS) were used to understand the source of these morphological differences as a function of calcination temperature. Additionally, the SEM images were manually segmented using Morphological Analysis for MAterials (MAMA) software to identify quantifiable differences in morphology for three different surface features present on the unwashed uranyl peroxide calcination products. No single quantifiable signature was sufficient to discern all calcination temperatures with a high degree of confidence; therefore, advanced statistical analysis was performed to allow the combination of a number of quantitative signatures, with their associated uncertainties, to allow for complete discernment by calcination history. Furthermore, machine learning was applied to the acquired SEM images to demonstrate automated discernment with at least 89% accuracy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The analytical techniques typically utilized in a nuclear forensic investigation often provide limited information regarding the process history and production conditions of interdicted nuclear material. In this study, scanning electron microscopy (SEM) analysis of the surface morphology of amorphous-UO 3 samples calcined at 250, 300, 350, 400, and 450°C from uranyl peroxide was performed to determine if the morphology was indicative of the synthesis route and thermal history for the samples. Thermogravimetic analysis-mass spectrometry (TGA-MS) and differential scanning calorimetry (DSC) were used to correlate transitions in the calcined material to morphological transformations. The high-resolution SEM images were processed using the Morphological Analysis for Material Attribution (MAMA) software. Morphological attributes, particle area and circularity, indicated significant trends as a result of calcination temperature. The quantitative morphological analysis was able to track the process of particle fragmentation and subsequent sintering as calcination temperature was increased. At the 90% confidence interval, with 1000 segmented particles, the use of Kolmogorov-Smirnov statistical comparisons allowed discernment between all calcination temperatures for the uranyl peroxide route., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Head injury is a leading cause of mortality in Africa. We characterise the epidemiology and outcomes of head injury at an Ethiopian emergency centre., Methods: We conducted a prospective cohort study of all head injured patients presenting to the Emergency Centre of Tikur Anbessa Specialised Hospital, Addis Ababa. Data was collected via a standardised form from the patient's chart, radiology reports and operative reports. Patients were followed until discharge, facility transfer, death, or 7 days in hospital. Consent was obtained from the patient or substitute decision maker., Results: Among 204 head injured patients enrolled, the majority were <30 years old (51.0%) and male (86.8%). Forty-one percent of injuries occurred from road traffic accidents (RTAs). A significant number of patients had at least one indicator of severe injury on presentation: 51 (25.0%) had a GCS < 9, 53 (26.0%) had multi-system trauma, 95 (46.6%) had ≥1 abnormal vital sign and of the 133 patients with data available, 37 (27.8%) had a Revised Trauma Score (RTS) < 6. Patients injured by RTA were more likely to have indicators of severe injury than other mechanisms, including multi-system trauma (OR 3.2, 95% CI 1.7-6.2, p = 0.00), GCS < 9 (OR 3.7, 95% CI 1.8-7.4, p = 0.00), ≥1 abnormal vital sign (OR 2.5, 95% CI 1.4-4.6, p = 0.00) or an RTS score < 6 (OR 3.6, 95% CI 1.6-8.1, p = 0.00). Overall, 149 (73.0%) patients were discharged from hospital, 34 (16.7%) were transferred to another hospital, and 21 patients died (10.3%). In multivariable analysis, death was significantly associated with age over 60 years (aOR 68.8, 95% CI 2.0-2329.0, p = 0.02), GCS < 9 (aOR 14.8, 95% CI 2.2-99.5, p = 0.01), fixed bilateral pupils (aOR 39.1, 95% CI 4.2-362.8, p < 0.01) and hypoxia (oxygen saturation <90%; aOR 14.2%, 95% CI 2.6-123.9, p = 0.01)., Conclusion: Head injury represents a significant risk for morbidity and mortality in Ethiopia, of which RTA's increase injury severity. Targeted approaches to improving care of the injured may improve outcomes.

The long-acting, highly lipophilic, β2-adrenoceptor agonist clenbuterol may represent a suitable therapeutic agent for the treatment of neuroinflammation as it drives an anti-inflammatory response within the CNS. However, clenbuterol is also known to increase the expression of IL-1β in the brain, a potent neuromodulator that plays a role in provoking sickness related symptoms including anxiety and depression-related behaviours. Here we demonstrate that, compared to the immunological stimulus lipopolysaccharide (LPS, 250μg/kg), clenbuterol (0.5mg/kg) selectively up-regulates expression of the central IL-1 system resulting in a mild stress-like response which is accompanied by a reduction in locomotor activity and food consumption in rats. We provide further evidence that clenbuterol-induced activation of the central IL-1 system occurs in a controlled and selective manner in tandem with its negative regulators IL-1ra and IL-1RII. Furthermore, we demonstrate that peripheral β2-adrenoceptors mediate the suppression of locomotor activity and food consumption induced by clenbuterol and that these effects are not linked to the central induction of IL-1β. Moreover, despite increasing central IL-1β expression, chronic administration of clenbuterol (0.03mg/kg; twice daily for 21days) fails to induce anxiety or depressive-like behaviour in rats in contrast to reports of the ability of exogenously administered IL-1 to induce these symptoms in rodents. Overall, our findings suggest that clenbuterol or other selective β2-adrenoceptor agonists could have the potential to combat neuroinflammatory or neurodegenerative disorders without inducing unwanted symptoms of depression and anxiety., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Preeclampsia is a disorder related to an imbalance in the angiogenesis axis manifesting as endothelial dysfunction. Animal and human studies have shown that sFLT-1 (soluble fms like tyrosine kinase 1) is increased and PlGF (placental growth factor) reduced during the disease state. There are a paucity of studies investigating the clinical significance of normalising angiogenic axis., Objectives: To use a non-human primate uteroplacental ischemic (UPI) model of preeclampsia to assess if reversing the angiogenic imbalance, by increasing circulating PlGF, is able to ameliorate the hypertension and proteinuria., Methods: Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by ligation of a unilateral uterine artery at 130days of an 182day pregnancy. After two weeks of UPI, PlGF was administered by subcutaneous injection (100mg/kg/day) for 5 days (n=3) or normal saline in an equivalent volume (n=3). Blood pressure was monitored via intra-arterial radiotelemetry, sFLT-1 measured via ELISA and spot urinary protein:creatinine ratios were measured to monitor proteinuria. Data was analysed using SPSS by t-tests and analysis of repeated measures. Significance was set at p<0.05 and data expressed as the mean ±SEM., Results: After two weeks of UPI both groups demonstrated a significant elevation in blood pressure, proteinuria (p<0.05) and sFLT-1 (p<0.001). The systolic BP increased by 12.4±2.3mmHg and 11.7±2.9mmHg in the PlGF and control groups respectively compared to baseline (p<0.005). After PlGF administration, there was a significant reduction in blood pressure in the treated group (-5.2s±0.8mmHg) compared to the increase in BP in the control group (+6.5±3mmHg). Proteinuria also reduced in the treated group from 112±51mg/mmol to 38±12mg/mmol whilst proteinuria in the control group was unchanged. The total circulating sFLT-1 was not significantly affected by the administration of PlGF after 5days. Although this study was not designed to assess fetal safety or outcomes, there was no adverse fetal outcome attributable to the administration of the PlGF., Conclusion: Administration of PlGF resulted in a reduction in BP and proteinuria without significantly affecting total sFLT-1 levels. Correcting the angiogenic axis imbalance may improve the clinical parameters in a non-human primate animal model of preeclampsia., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Experimental manipulation of the maternal environment in animal models has assisted with our understanding of the mechanisms contributing to fetal programming. Evidence suggests that individuals who experience a suboptimal intrauterine milieu have an increased risk of developing disease later in life. Preeclampsia is a complication of pregnancy known to alter the fetal environment. Such alterations lead to programming of the fetus for subsequent susceptibility to cardiovascular disease, including hypertension. Studies indicate that offspring from women with hypertensive disorders of pregnancy are at an increased risk of cardiovascular complications later in life., Objectives: To investigate whether offspring of experimental preeclamptic baboon pregnancies have higher blood pressure compared with offspring of their experimental controls and those of normotensive pregnancies. This is a pilot study to assess the feasibility of measuring health outcomes and risk factors for experimental preeclampsia offspring., Methods: We have successfully developed two models of preeclampsia in the baboon (Papio hamadryas) through induction of uteroplacental ischemia in late pregnancy and TNFα infusion mid pregnancy. Systolic and diastolic blood pressure (SBP, DBP) were measured in baboon offspring from experimental preeclamptic (EPE, n=4), experimental preeclamptic control (EPE control, n=4) and normotensive pregnancies (Normal, n=12) using indirect sphygmomanometry (first and fourth Korotkoff sounds recorded). Each measurement was taken three times under identical anaesthetic and environmental conditions. Data are reported as the average ± standard deviation. A generalized linear model was applied to the data and adjusted for age and sex., Results: There was no significant difference in SBP of offspring from EPE (97.3±7.2mm Hg, P=0.21) or EPE control (108.4±7.3mm Hg, P=0.16) when compared with offspring of normotensive pregnancies (102.6±7.3mm Hg). Similarly, there was no difference in DBP of offspring from EPE (67.5±15.4 mm Hg, P=0.72) or EPE control (61.5±15.7mm Hg, P=0.79) compared with normotensive offspring (63.9±16.7mm Hg). There was a significant difference in SBP and DBP of young (<5yrs) compared to older (⩾5yrs) animals (SBP: 96.4±7.9 versus 109.1±7.5mm Hg, P=0.003; DBP: 54.3±17.2 versus 74.4±16.4mm Hg, P=0.009). There were no differences in SBP or DBP between male and female offspring (102.1±7.7 versus 103.4±8.3mm Hg, P=0.70; 63.9±16.8 versus 64.8±18.4mm Hg, P=0.90 respectively)., Conclusion: This study has shown that offspring from experimental preeclamptic pregnancies survive and are able to undergo long-term testing of blood pressure. There does not appear to be any significant differences in blood pressure among EPE offspring and their controls. However, the opportunity to investigate offspring over an extended period of time is feasible. This will enable us to examine other parameters that affect BP of experimental preeclampsia offspring., (Copyright © 2012. Published by Elsevier B.V.)