Notes

COVID-19 along with Coronary disease: a Global Viewpoint.
There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus.

The neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.
The neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.Coronavirus Disease 2019 (COVID-19) pandemic-triggered mortality is significantly higher in older than in younger populations worldwide. Alzheimer's disease (AD) is related to aging and was recently reported to be among the major risk factors for COVID-19 mortality in older people. The symptomatology of COVID-19 indicates that lethal outcomes of infection rely on neurogenic mechanisms. The present review compiles the available knowledge pointing to the convergence of COVID-19 complications with the mechanisms of autonomic dysfunctions in AD and aging. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is prone to neuroinvasion from the lung along the vagus nerve up to the brainstem autonomic nervous centers involved in the coupling of cardiovascular and respiratory rhythms. The brainstem autonomic network allows SARS-CoV-2 to trigger a neurogenic switch to hypertension and hypoventilation, which may act in synergy with aging- and AD-induced dysautonomias, along with an inflammatory "storm". The lethal outcomes of COVID-19, like in AD and unhealthy aging, likely rely on a critical hypoactivity of the efferent vagus nerve cholinergic pathway, which is involved in lowering cardiovascular pressure and systemic inflammation tone. We further discuss the emerging evidence supporting the use of 1) the non-invasive stimulation of vagus nerve as an additional therapeutic approach for severe COVID-19, and 2) the demonstrated vagal tone index, i.e., heart rate variability, via smartphone-based applications as a non-serological low-cost diagnostic of COVID-19. These two well-known medical approaches are already available and now deserve large-scale testing on human cohorts in the context of both AD and COVID-19.
Recent evidence suggests that the accumulation of iron, specifically ferrous Fe
, may play a role in the development and progression of neurodegeneration in Alzheimer's disease (AD) through the production of oxidative stress.

To localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology.

We perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of specific iron-rich regions of interest.

Specific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the depositsular interactions between Aβ, tau, iron, and other putative metals, such as zinc.
These findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Necrostatin 2 in vitro Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Aβ, tau, iron, and other putative metals, such as zinc.
Alzheimer's disease (AD) is the 6th leading cause of death in the United States and has no cure or progression prevention. The Cognitive Reserve (CR) theory poses that constant brain activity earlier in life later helps to deter pathological changes in the brain, delaying the onset of disease symptoms.

To determine the reliability and validity of the Cognitive Reserve Index questionnaire (CRIq) in AD patients.

Primary data collection was done using the CRIq to quantify CR in 90 participants. Correlations and multivariable linear regressions were used to assess reliability and validity.

Reliability was tested in 34 participants. A Pearson correlation coefficient of 0.89 (
 < 0.001) indicated a strong positive correlation. Validity was tested in 33 participants. A Pearson correlation coefficient of 0.30 (
 = 0.10) indicated an insignificant weak positive correlation.

The CRIq was found reliable. Gaining a better understanding of how CR tools can be used in various cognitive populations will help with the establishment of a research tool that is universally accepted as a true CR measure.
The CRIq was found reliable. Gaining a better understanding of how CR tools can be used in various cognitive populations will help with the establishment of a research tool that is universally accepted as a true CR measure.Porphyromonas gingivalis (P. gingivalis) is one of the several important bacterial pathogens associated with the sporadic Alzheimer's disease (AD). Different serotypes are either capsulated or are non-capsulated. It has been demonstrated that P. gingivalis (non-capsulated) can reproduce the neurodegenerative AD-like changes in vitro, and a capsular P. gingivalis (strain W83) could reproduce the cardinal hallmark lesions of AD in a wild-type mouse model. All P. gingivalis forms express proteolytically active proteases that enable cleavage of the amyloid-β protin precursor (AβPP) and tau resulting in the formation of amyloid-β and neurofibrillary tangles. Tau is an established substrate for gingipains, which can cleave tau into various peptides. Some of the P. gingivalis fragmented tau protein peptides contain "VQIINK" and "VQIVYK" hexapeptide motifs which map to the flanking regions of the microtubule binding domains and are also found in paired helical filaments that form NFTs. P. gingivalis can induce peripheral inflammation in periodontitis and can also initiate signaling pathways that activate kinases, which in turn, phosphorylate neuronal tau. Periodontal disease related inflammation has metabolic implications for an individual's peripheral and brain health as patients suffering from generalized periodontitis often have related co-morbidities and are "at risk" of developing AD. The aim here is to discuss the role of P. gingivalis behind such associations with the backdrop of huge efforts to test P. gingivalis virulence factors clinically (GAIN Trial Phase 2/3 Study of COR388 in Subjects with AD) with inhibitors, which may lead to an intervention by reducing the pathogenic bacterial load.Handgrip dynamometers are used to assess handgrip strength (HGS), and low HGS is linked to poor cognitive function. Although HGS is a reliable measure of muscle function, it is only measuring maximal grip force. Other aspects of muscle function such as force control, fatigability, and steadiness are unaccounted for in current HGS protocols. This pilot study sought to determine the role of maximal HGS, submaximal HGS force control, HGS fatigability, and HGS neuromuscular steadiness on cognitive function in older adults. Our findings indicate that these additional HGS measurements could factor into detecting poorer cognitive functioning, while also evolving HGS protocols.Kawasaki disease (KD) is an acute, self-limiting febrile illness of childhood associated with vasculitis, mainly of the medium-sized arteries. The clinical significance and impact of this condition arise from its predilection for the coronary arteries. The criteria for classic Kawasaki disease are clearly defined, but many children present with atypical forms, and clinicians need to consider this possibility. Although most diagnosed cases respond to intravenous immunoglobulin (IVIG) and aspirin, some have proven resistant to the standard treatment. This article aims to provide a brief overview of Kawasaki disease, focusing on the resistant/refractory cases, and the treatment options available for such cases.
The Bezold-Jarisch reflex (BJR) is a cardioinhibitory parasympathetic response to activation of ventricular mechanoreceptors, which can result in bradycardia, atrioventricular block, or asystole. This phenomenon has been triggered by acute myocardial ischaemia, intra-arterial nitroglycerine use, natriuretic peptides, and with exceptional rarity, in middle-aged women only, by dobutamine infusion during stress echocardiography.

We present the case of a 61-year-old woman who suffered a 5.1-s sinus pause during her 20 μg/kg/min infusion of dobutamine. Recovery was immediate following termination of dobutamine infusion. Concurrent echocardiography was normal, and subsequent cardiac catheterization and electrophysiologic study were normal.

This is the fifth documented case of a severe BJR causing asystole during dobutamine infusion, which adds to the accumulating evidence supporting the benign nature of the condition.
This is the fifth documented case of a severe BJR causing asystole during dobutamine infusion, which adds to the accumulating evidence supporting the benign nature of the condition.Introduction  The risk of venous thromboembolism (VTE) increases during pregnancy and the puerperium such that VTE is a leading cause of maternal mortality. Methods  We describe the clinical characteristics, diagnostic strategies, treatment patterns, and outcomes of women with pregnancy-associated VTE (PA-VTE) enrolled in the Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE. Women of childbearing age ( less then 45 years) were stratified into those with PA-VTE ( n  = 183), which included pregnant patients and those within the puerperium, and those with nonpregnancy associated VTE (NPA-VTE; n  = 1,187). Patients with PA-VTE were not stratified based upon the stage of pregnancy or puerperium. Results  Women with PA-VTE were younger (30.5 vs. 34.8 years), less likely to have pulmonary embolism (PE) (19.7 vs. 32.3%) and more likely to have left-sided deep vein thrombosis (DVT) (73.9 vs. 54.8%) compared with those with NPA-VTE. The most common risk factors in PA-VTE patients were hospitalization (10.4%), previous surgery (10.4%), and family history of VTE (9.3%). DVT was typically diagnosed by compression ultrasonography (98.7%) and PE by chest computed tomography (75.0%). PA-VTE patients more often received parenteral (43.2 vs. 15.1%) or vitamin K antagonists (VKA) (9.3 vs. 7.6%) therapy alone. NPA-VTE patients more often received a DOAC alone (30.2 vs. 13.7%). The risk (hazard ratio [95% confidence interval]) of all-cause mortality (0.59 [0.18-1.98]), recurrent VTE (0.82 [0.34-1.94]), and major bleeding (1.13 [0.33-3.90]) were comparable between PA-VTE and NPA-VTE patients. Uterine bleeding was the most common complication in both groups. Conclusion  VKAs or DOACs are widely used for treatment of PA-VTE despite limited evidence for their use in this population. Rates of clinical outcomes were comparable between groups.
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