Spontaneous globe rupture in a patient with extensive ocular surgical history.

Globe rupture is visually dramatic in appearance for emergency clinicians and is a sight-threatening injury for the patient. It requires prompt ophthalmologic surgical intervention for optimal outcomes. Cases are typically the result of ocular trauma; however, this case highlights a rare instance of spontaneous globe rupture in a patient with an extensive ocular surgical history.

Applying a tiered environmental risk assessment framework to estimate the risk of pesticides to soil organisms in Latin America.

This work investigates the application of a tiered risk assessment scheme for soil organisms based on the risk quotient (RQ) and the toxicity exposure ratio (TER). Forty-five pesticides registered in Latin America were chosen and the ecotoxicological endpoints for earthworms, Collembola, and microorganisms were collated. Tier I assessment was made on conservative assumptions in which no refinements were applied. There, 14 pesticides (31%) exceed the RQ regulatory trigger indicating unacceptable risk, whereas 27 (60%) indicate unacceptable risk on the TER approach. In a Tier II evaluation when refinement options such as foliar interception, field half-life, and the dissipation following the peak estimated environmental concentration are considered, eight (18%) pesticides indicate unacceptable risk based on the RQ, and 15 (33%) indicate unacceptable risk based on the TER. A nonmetric multidimensional scaling evaluation was performed to understand the relevant characteristics involved in how each pesticide poses a risk to soil organisms. Based on the outcome of this analysis, we observed that, for a given pesticide, the combination of high persistence, low or no crop interception, and high toxicity are likely to require higher tier risk assessment. Refinement options can consider either or both the exposure and/or the effect side of the framework. Exposure refinements are potentially simpler and can be conducted with data already available to risk assessors, whereas effect refinements involving further testing with the organisms potentially at risk are still under discussion for intermediate and higher tiers. A sensitive, simple, and logical environmental risk assessment framework can be used to adequately identify risks based on the relevant protection goals that, in turn, will help to protect the desired soil multifunctionality of the ecosystem. We encourage academia and industry to further investigate these topics to provide the most scientifically robust and evidence-based information to decision makers. Integr Environ Assess Manag 2023;19:446-460. © 2022 SETAC.

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers.

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.

The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats.

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.

Ingestion of lean meat elevates muscle inositol hexakisphosphate kinase 1 protein content independent of a distinct post-prandial circulating proteome in young adults with obesity.

BACKGROUND: We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS: We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS: Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ±â€¯0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ±â€¯0.17], 10 overweight (BMI: 27.1 ±â€¯0.5; HOMAIR: 1.25 ±â€¯0.11), and 10 obese (BMI: 35.9 ±â€¯1.3; HOMAIR: 5.82 ±â€¯0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS: Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS: These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.

High-Intensity Exercise Decreases IP6K1 Muscle Content and Improves Insulin Sensitivity (SI2*) in Glucose-Intolerant Individuals.

Context: Insulin resistance (IR) in skeletal muscle contributes to whole body hyperglycemia and the secondary complications associated with type 2 diabetes. Inositol hexakisphosphate kinase-1 (IP6K1) may inhibit insulin-stimulated glucose transport in this tissue type. Objective: Muscle and plasma IP6K1 were correlated with two-compartment models of glucose control in insulin-resistant hyperinsulinemic individuals. Muscle IP6K1 was also compared after two different exercise trials. Design: Nine prediabetic [hemoglobin A1c; 6.1% (0.2%)] patients were recruited to take part in a resting control, a continuous exercise (90% of lactate threshold), and a high-intensity exercise trial (6 30-second sprints). Muscle biopsies were drawn before and after each 60-minute trial. A labeled ([6,62H2]glucose) intravenous glucose tolerance test was performed immediately after the second muscle sample. Results: Fasting muscle IP6K1 content did not correlate with insulin sensitivity (SI2*) (P = 0.961). High-intensity exercise reduced IP6K1 muscle protein and messenger RNA expression (P = 0.001). There was no effect on protein IP6K1 content after continuous exercise. Akt308 phosphorylation of was significantly greater after high-intensity exercise. Intermittent exercise reduced hepatic glucose production after the same trial. The same intervention also increased SI2*, and this effect was significantly greater compared with the effect of continuous exercise improvements. Our in vitro experiment demonstrated that the chemical inhibition of IP6K1 increased insulin signaling in C2C12 myotubes. Conclusions: The in vivo and in vitro approaches used in the current study suggest that a decrease in muscle IP6K1 may be linked to whole body increases in SI2*. In addition, high-intensity exercise reduces hepatic glucose production in insulin-resistant individuals.

The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial.

BACKGROUND AND PURPOSE: Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. METHODS: The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke-funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 microg/kg bolus followed by 0.75 microg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. RESULTS: Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA-only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. CONCLUSIONS: The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.