Annals of medicine
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Introduction: Several neurodegenerative conditions are associated with a common histopathology within neurons of the central nervous system, consisting of the deposition of cytoplasmic inclusions of TAR DNA-binding protein 43 (TDP-43). Such inclusions have variably been described as morphologically and molecularly ordered aggregates having amyloid properties, as filaments without the cross-β-structure and dye binding specific for amyloid, or as amorphous aggregates with no defined structure and fibrillar morphology. Aims and Methods: Here we have expressed human full-length TDP-43 in neuroblastoma x spinal cord 34 (NSC-34) cells to investigate the morphological, structural, and tinctorial properties of TDP-43 inclusions in situ. ⋯ It cannot be excluded that filaments emerge on the long time scale from such inclusions, but the high propensity of the protein to form initially other types of inclusions appear to be an essential characteristic of TDP-43 proteinopathies. KEY MESSAGESCytoplasmic inclusions of TDP-43 formed in NSC-34 cells do not stain with amyloid-diagnostic dyes, are not enriched with cross-β structure, and do not show a fibrillar morphology. TDP-43 assemblies formed in vitro from pure TDP-43 do not have any hallmarks of amyloid.
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Despite recommendations for influenza and COVID-19 vaccines, studies have documented gaps and disparities in vaccination coverage for adults and adolescents. Understanding the proportion and demographics of those unvaccinated against influenza and/or COVID-19 is important for tailoring appropriate messaging and strategies to increase confidence and uptake. ⋯ During the COVID-19 pandemic, approximately two-thirds of adolescents and three-fourths of adults received exclusive influenza or COVID-19 vaccines or both vaccines in 2021. Vaccination patterns differed by sociodemographic and other characteristics. Promoting confidence in vaccines and reducing barriers to access is needed to protect individuals and families from severe health consequences of vaccine-preventable diseases. Being up-to-date with all recommended vaccinations can prevent a future resurgence of hospitalizations and cases.Key messages42.5% of adults and 28.3% of adolescents received both influenza and COVID-19 vaccines in 2021, while approximately a quarter (22.4%) of adults and a third (34.0%) of adolescents did not receive either vaccine; 6.0% of adults and 11.4% of adolescents were exclusively vaccinated against influenza and 29.1% of adults and 26.4% of adolescents were exclusively vaccinated against COVID-19.Among adults, exclusive COVID-19 vaccination or dual vaccination was more likely to be associated with older age, non-Hispanic multi/other race, and having a college degree or higher compared to their respective counterparts; exclusive influenza vaccination or neither vaccination was more likely to be associated with younger age, having a high school diploma or less, living below poverty level, and having a previous COVID-19 diagnosis compared to their respective counterparts.Promoting confidence in vaccines and reducing barriers to access is needed to protect individuals and families from severe health consequences of vaccine-preventable diseases. Being up-to-date with all recommended vaccinations can prevent a future resurgence of hospitalizations and cases, especially as new variants emerge.
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It has been discovered that a folate shortage may raise the risk of hepatic steatosis. We investigated the relationship between serum folate and controlled attenuation parameter (CAP) among 3606 participants over from the National Health and Nutrition Examination Survey (NHANES). ⋯ According to our study, the majority of Americans, particularly men and whites, had a negative correlation between serum folate and CAP. Among white people, this connection followed an U-shaped pattern. These findings may provide guidance for monitoring serum folate level and controlling oral folate dosage in clinic, so as to prevent liver steatosis more effectively.Key MessagesThe size of the cohort in our study is large, and our findings come from a nationally representative database.Our study revealed a negative relationship between serum folate and CAP among most Americans, especially in male and whites, which may provide evidence for medications to treat hepatic steatosis.In whites, the association of serum folate with CAP was an U-shaped curve (inflection point: 34 ng/ml). This may provide guidance for monitoring serum folate level and controlling oral folate dosage in clinic, so as to prevent liver steatosis more effectively.
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Observational Study
Anterior segment inflammation and its association with dry eye parameters following myopic SMILE and FS-LASIK.
To evaluate dry eye and anterior segment inflammation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and investigate their association. ⋯ Both SMILE and FS-LASIK induced elevated anterior chamber flare and dry eye. However, flare might not be considered a factor determining perioperative dry eye.Key MessagesDry eye disease is common after corneal refractive surgery. Signs and symptoms of dry eye disease persist longer after FS-LASIK compared with SMILE.Both FS-LASIK and SMILE transiently disrupted blood-aqueous barrier integrity, leading to anterior segment inflammation.Anterior chamber flare might not be considered a factor explaining perioperative dry eye, other biomarkers remain for future exploration.
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Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro α-thrombin-evoked (10 μM/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes. ⋯ From the current descriptive work only involving type 2 diabetes, it is impossible to judge whether the findings are features of the disease or if they occur in healthy individuals as well. However, the study describes LAMP-1 expressing subpopulations of circulating normal-sized platelets that associate with WB α-thrombin (10 U/mL) responses in vitro. Increased proportions of such platelets induced lysosomal release and αIIbβ3 receptor activity, whereas lower proportions promoted WB agonist-induced procoagulant platelet creation. It is to hypothesize that the new described regulatory mechanism could in the future offer a possibility to influence platelet behavior in type 2 diabetes.Key messagesLysosomal exocytosis of circulating platelets influences reactivity, as determined by agonist-induced platelet reactions in vitroThus, the low release of lysosomes by normal-sized platelets in vivo increases agonist-evoked procoagulant platelet production.Higher lysosomal exocytosis of circulating normal-sized platelets promotes platelet aggregation and secretion.