Changes in the locus coeruleus during the course of Alzheimer's disease and their relationship to cortical pathology.

AIMS: In Alzheimer's disease (AD), the locus coeruleus (LC) undergoes early and extensive neuronal loss, preceded by abnormal intracellular tau aggregation, decades before the onset of clinical disease. Neuromelanin-sensitive MRI has been proposed as a method to image these changes during life. Surprisingly, human post-mortem studies have not examined how changes in LC during the course of the disease relate to cerebral pathology following the loss of the LC projection to the cortex. METHODS: Immunohistochemistry was used to examine markers for 4G8 (pan-Aß) and AT8 (ptau), LC integrity (neuromelanin, dopamine ß-hydroxylase [DßH], tyrosine hydroxylase [TH]) and microglia (Iba1, CD68, HLA-DR) in the LC and related temporal lobe pathology of 59 post-mortem brains grouped by disease severity determined by Braak stage (0-II, III-IV and V-VI). The inflammatory environment was assessed using multiplex assays. RESULTS: Changes in the LC with increasing Braak stage included increased neuronal loss (p < 0.001) and microglial Iba1 (p = 0.005) together with a reduction in neuromelanin (p < 0.001), DßH (p = 0.002) and TH (p = 0.041). Interestingly in LC, increased ptau and loss of neuromelanin were detected from Braak stage III-IV (p = 0.001). At Braak stage V/VI, the inflammatory environment was different in the LC vs TL, highlighting the anatomical heterogeneity of the inflammatory response. CONCLUSIONS: Here, we report the first quantification of neuromelanin during the course of AD and its relationship to AD pathology and neuroinflammation in the TL. Our findings of neuromelanin loss early in AD and before the neuroinflammatory reaction support the use of neuromelanin-MRI as a sensitive technique to identify early changes in AD.

A Rare Case of ST-Segment Elevation Myocardial Infarction and Left Ventricular Thrombus in a Dextrocardia Patient With COVID-19 Infection.

Acute coronary syndrome (ACS) is an increasingly common finding among patients presenting with Coronavirus Disease 2019 (COVID-19) pneumonia. While cardiovascular disease alone remains one of the most common causes of death among COVID-19 patients in the United States, its heightened prevalence with COVID-19 pneumonia has been well documented. Here we present the case of a 58-year-old male with an extensive cardiac history including coronary artery disease (CAD) with multiple drug-eluting stents (DES) placed and an episode of cardiac arrest requiring implantable cardioverter defibrillator (ICD) placement. He presented to the Emergency Department originally complaining of chest pain, shortness of breath, and fatigue, and was found to be positive for COVID-19 pneumonia. Cardiac catheterization demonstrated extensive CAD and evaluation for coronary artery bypass grafting (CABG) was warranted. Shortly after, the patient experienced an acute thrombotic episode in the left anterior descending (LAD) coronary artery and underwent successful emergent high-risk percutaneous coronary intervention (PCI) with DES placement. The patient was also found to have a left ventricular thrombus requiring anticoagulation. Despite his complex course, the patient had a very favorable outcome.

Carbohydrate mouth rinse improves resistance exercise capacity in the glycogen-lowered state.

The effect of carbohydrate mouth rinse (CHO MR) on resistance exercise performance is equivocal and may be moderated by carbohydrate availability. This study determined the effect of CHO MR on low-load resistance exercise capacity completed in a fed but glycogen-lowered state. Twelve resistance-trained men (age: 22 ± 4 years; height: 1.79 ± 0.05 m; mass: 78.7 ± 7.8 kg; bench press one-repetition maximum (1RM): 87 ± 21 kg; squat 1RM: 123 ± 19 kg) completed two fed-state resistance exercise bouts consisting of six sets of bench press and six sets of squat to failure at 40% 1RM. Each bout was preceded by glycogen-depleting cycling the evening before, with feeding controlled to create acute energy deficit and maintain low muscle glycogen. During resistance exercise, participants rinsed with either a 6% CHO MR solution or a taste-matched placebo (PLA) between sets. Total volume workload was greater with CHO MR (9354 ± 2051 vs. 8525 ± 1911 kg, p = 0.010). Total number of repetitions of squat were greater with CHO MR (107 ± 26 vs. 92 ± 16, p = 0.017); the number of repetitions of bench press were not significantly different (CHO MR: 120 ± 24 vs. PLA: 115 ± 22, p = 0.146). This was independent of differences in feeling or arousal. CHO MR may be an effective ergogenic aid for athletes completing resistance exercise when in energy deficit and with low carbohydrate availability. Novelty: CHO MR can increase low-load resistance exercise capacity undertaken in a glycogen-lowered but fed state. This effect was driven by a greater number of repetitions-to-failure in the squat - using muscles lowered in glycogen content with exhaustive cycling on the evening prior to resistance exercise - but not bench press.