👤 Paola Sebastiani

A signature of 16 serum proteins that were previously profiled using the aptamer-based Somascan technology highlighted the roles of the e2 allele of APOE in lipid regulation via apolipoprotein B (APOB) and apolipoprotein E (APOE) and in inflammation. Here, the serum protein signature of APOE is validated and expanded using a combination of mass-spectrometry, ELISA, Luminex, blood transcriptomics, and antibody-based Olink serum proteomics. Some of the findings were replicated in the UK Biobank using antibody-based Olink serum proteomics. This analysis replicated the association between APOB and the e2 allele of APOE, detected a new, robust pattern of association between APOE genotypes and the serum level of APOE, and discovered new associations between APOE genotypes and the complex of apolipoproteins APOC1, APOC2, APOC3, APOC4, APOE, APOF, and APOL1. In addition, 13 new proteins correlated with APOE genotypes. This extended signature includes granule proteins CAMP, CTSG, DEFA3, and MPO secreted from neutrophils and points to olfactomedin 4 (OLFM4) as a new target for the prevention of Alzheimer's disease. Show less

Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor, with a growing recognized role in stroke. To investigate the association between Lp(a) levels, large artery atherosclerosis (LAA) TOAST (Trial of ORG 10172 in Acute Stroke Treatment) category, and stroke-related atherosclerosis distribution (extracranial/intracranial) in a single-center retrospective cohort of patients with ischemic stroke. We included all patients with ischemic stroke admitted between March and December 2021 with Lp(a) levels and computed tomography angiography. Multivariable regression assessed the relationship between Lp(a) and LAA, extracranial carotid stenosis, or intracranial atherosclerotic stenosis (ICAS). Predicted probabilities of atherosclerosis location per Lp(a) increment were estimated from a multinomial logistic regression model. We screened 523 patients and included 397 with complete data. The median age was 78 years, and 47% were female. Median Lp(a) was significantly higher in patients with stroke-related atherosclerosis, particularly those with intracranial involvement. Statin use (adjusted β = 15.01, 95% CI: 3.32-26.70, P = .012) and low-density lipoprotein levels (adjusted β = 0.236, 95% CI: 0.09-0.38, P = .002) were independently associated with Lp(a). Lp(a) was significantly associated with LAA (per 10 mg/dL increment: adjusted odds ratio [OR]: 1.08, 95% CI: 1.03-1.14, P = .003; for Lp(a) ≥50 mg/dL vs <50 mg/dL, LAA prevalence was 27% vs 15%, P = .007; adjusted OR: 2.71, 95% CI: 1.47-5.91, P = .001). Lp(a) ≥50 mg/dL was significantly associated with ICAS (adjusted OR: 4.49, 95% CI: 2.41-8.38, P < .001), but not with extracranial carotid stenosis (P = .065). With increasing Lp(a) levels, ICAS showed the steepest increase in predicted probability. Higher Lp(a) values are associated with LAA stroke, particularly ICAS. Lp(a) levels should be included in the stroke workup. Show less

We previously identified a signature of 16 serum proteins that highlighted a role of the e2 allele of APOE in lipid regulation via apolipoprotein B (APOB) and apolipoprotein E (APOE), and in inflammation. The serum proteins were profiled using the aptamer-based Somalogic technology. Here, we validate and expand the serum protein signature of APOE using a combination of mass-spectrometry, ELISA, Luminex, antibody-based Olink proteomics, and blood transcriptomics. We replicate the association between APOB and the e2 allele of APOE, we correct the pattern of association between APOE genotypes and serum level of APOE, and we detect new associations between APOE genotypes and the complex of apolipoproteins APOC1, APOC4, APOC2, APOC3, APOE, APOF and APOL1. In addition, we discover 13 new proteins that correlate with APOE genotypes. This extended signature includes granule proteins CAMP, CTSG, DEFA3, and MPO secreted from neutrophils and points to olfactomedin 4 (OLFM4) as a new target for the prevention of Alzheimer's disease. Show less

NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO). Five hundred and eighty-two consecutive patients with biopsy-proven NAFLD or a clinical diagnosis of NAFLD-related compensated cirrhosis were classified as hepatocellular (H), C and mixed (M) patterns, by using the formula (ALT/ALT Upper Limit of Normal-ULN)/(ALP/ALP ULN). MALO were recorded during follow-up. An external cohort of 1281 biopsy-proven NAFLD patients was enrolled as validation set. H, M and C patterns were found in 153 (26.3%), 272 (46.7%) and 157 (27%) patients respectively. During a median follow-up of 78 months, only 1 (0.6%) patient with H pattern experienced MALO, whilst 15 (5.5%) and 38 (24.2%) patients in M and C groups had MALO. At multivariate Cox regression analysis, age >55 years (HR 2.55, 95% CI 1.17-5.54; p = .01), platelets <150 000/mmc (HR 0.14, 95% CI 0.06-0.32; p < .001), albumin <4 g/L(HR 0.62, 95% CI 0.35-1.08; p = .09), C versus M pattern (HR 7.86, 95% CI 1.03-60.1; p = .04), C versus H pattern(HR 12.1, 95% CI 1.61-90.9; p = .01) and fibrosis F3-F4(HR 35.8, 95% CI 4.65-275.2; p < .001) were independent risk factors for MALO occurrence. C versus M pattern(HR 14.3, 95% CI 1.90-105.6; p = .008) and C versus H pattern (HR 15.6, 95% CI 2.10-115.1; p = .0068) were confirmed independently associated with MALO occurrence in the validation set. The immunohistochemical analysis found a significantly higher prevalence of moderate-high-grade ductular metaplasia combined with low-grade ductular proliferation in C pattern when compared with the biochemical H pattern. Gene expression analysis showed a lower expression of NR1H3, RXRα and VCAM1 in patients with the C pattern. The presence of a cholestatic pattern in patients with NAFLD predicts a higher risk of MALO independently from other features of liver disease. Show less

The goal of an infection control program is to provide a safe working environment for dental health care personnel and their patients. Practitioners can achieve this by adopting measures that reduce health care-associated infections among patients and occupational exposures among dental health care personnel. It is crucial for all dental practitioners to be up to date on current Centers for Disease Control and Prevention guidelines, equipment, and techniques for proper infection control. Continuous evaluation of infection control practices is important. Patients and dental providers should be confident that oral health care can be delivered and received in a safe manner. Show less

This article highlights the commonly used medications used in dentistry and oral surgery. General dentists and specialists must be knowledgeable about the pharmacology of the drugs currently available along with their risks and benefits. Enteral sedation is a useful adjunct for the treatment of anxious adult and pediatric patients. When enteral sedation is used within the standards of care, the interests of the public and the dental profession are served through a cost-effective, effective service that can be widely available. Oral sedation enables dentists to provide dental care to millions of individuals who otherwise would have unmet dental needs. Show less