Mechanically functional amyloid fibrils in the adhesive of a marine invertebrate as revealed by Raman spectroscopy and atomic force microscopy

Amyloid fibrils are primarily known in a pathogenic context for their association with a wide range of debilitating human diseases. Here we show a marine invertebrate (Entobdella soleae) utilizes functional amyloid fibrils comparable to those of a unicellular prokaryote (Escherichia coli). Thioflavin-T binding and Raman spectroscopy provided evidence for the presence of amyloid in the adhesive of Entobdella soleae. We elucidated that for these two very different organisms, amyloid fibrils provide adhesive and cohesive strength to their natural adhesives. Comparing the nanoscale mechanical responses of these fibrils with those of pathogenic amyloid by atomic force microscopy revealed that the molecular level origin of the cohesive strength was associated with the generic intermolecular β-sheet structure of amyloid fibrils. Functional adhesive residues were found only in the case of the functional amyloid. Atomic force microscopy provided a useful means to characterize the internal structural forces within individual amyloid fibrils and how these relate to the mechanical performance of both functional and pathogenic amyloid. The mechanistic link of amyloid-based cohesive and adhesive strength could be widespread amongst natural adhesives, irrespective of environment, providing a new strategy for biomimicry and a new source of materials for understanding the formation and stability of amyloid fibrils more generally.     

Takotsubo syndrome after cardiac surgery

We have not found any reports to date of Takotsubo syndrome after cardiac surgery. Recently described Takotsubo syndrome is characterized by acute reversible left ventricular dysfunction with apical ballooning in the absence of coronary artery disease, and with chest pain and electrocardiographic changes mimicking acute anterior myocardial infarction, but with minimal release of myocardial enzymes. We describe Takotsubo syndrome that developed after elective mitral valve replacement and tricuspid annuloplasty in a 62-year-old woman. On supportive therapy with vasopressors, left ventricular function gradually improved with an ejection fraction returning to 50%. Takotsubo cardiomyopathy should be considered as a possible complication of the cardiac surgery.     

In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance

Liver gene transfer is a highly sought goal for the treatment of inherited and infectious diseases. Lentiviral vectors (LVs) have many desirable properties for hepatocyte-directed gene delivery, including the ability to integrate into nondividing cells. Unfortunately, upon systemic administration, LV transduces hepatocytes relatively inefficiently compared with nonparenchymal cells, and the duration of transgene expression is often limited by immune responses. Here, we investigated the role of innate antiviral responses in these events. We show that administration of LVs to mice triggers a rapid and transient IFNalphabeta response. This effect was dependent on functional vector particles, and in vitro challenge of antigen-presenting cells suggested that plasmacytoid dendritic cells initiated the response. Remarkably, when LVs were administered to animals that lack the capacity to respond to IFNalphabeta, there was a dramatic increase in hepatocyte transduction, and stable transgene expression was achieved. These findings indicate that, even in the setting of acute delivery of replication-defective vectors, IFNs effectively interfere with transduction in a cell-type-specific manner. Moreover, because disabling a single component of the innate/immune network was sufficient to establish persistent xenoantigen expression, our results raise the hope that the immunologic barriers to gene therapy are less insurmountable than expected.     

Long-term changes in serum cholesterol level does not influence the progression of coronary calcification

BackgroundA number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC.MethodsThe study population comprised 510 patients with stable angina pectoris, mean age of 63 ± 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up.ResultsCL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups (p = 0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 ± 63 from baseline in the 1st (upper) quartile, and by 350 ± 44, 403 ± 41 and 480 ± 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes (p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups (p = 0.4). Multivariate analysis demonstrated that only baseline TCS (p < 0.001), body mass index (p = 0.007) and age (p = 0.006) were independent predictors for the TCS changes.ConclusionsLongitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC.     

Pattern of Blood Pressure Response in Patients With Severe Asymptomatic Hypertension Treated in the Emergency Department

Severe asymptomatic hypertension (SAH) is a common cause of emergency department (ED) visits. Despite recommendations against using short‐acting blood pressure (BP)–lowering drugs in the ED, it is still a common practice. The authors characterized BP response in the ED utilizing 24‐hour ambulatory BP monitoring (ABPM). Patients with SAH who were not admitted to the hospital were recruited. All patients underwent 24‐hour ABPM. A total of 21 patients (14 females) with a mean age of 58±16 years were studied. BP decreased from 199±16/101±17 mm Hg to 154±34/83±23 mm Hg after 5 hours but then rose to 174±25/94±17 mm Hg after 19 hours. In 17 patients, systolic BP was ≥180 mm Hg after 6.7±5.3 hours. Two patients experienced severe hypotension (systolic BP <90 mm Hg). Thus, data from a single site in Israel support the current recommendations for management of SAH in the ED.     

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019

We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.