RESUMO
Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto dSTORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm2. Our dSTORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status.
RESUMO
PURPOSE: To evaluate perinatal outcomes and long-term neurological morbidity of offspring to mothers with a history of ectopic pregnancy. METHODS: In this retrospective study, perinatal outcomes and long-term neurological morbidity of offspring were assessed among mothers with a history of ectopic pregnancy, either medically or surgically treated. The study groups were followed until 18 years of age for neurological-related morbidity. For perinatal outcomes, generalized estimated equation (GEE) models were used to control for confounders. A Kaplan-Meier survival curve was used to compare cumulative neurological morbidity incidence and Cox proportional hazards model was conducted to control for confounders. RESULTS: A total of 243,682 mothers were included; 1424 mothers (0.58%) had a previous ectopic pregnancy, of which 25.6% (n = 365) were treated medically, and 74.3% (n = 1059) were treated surgically. Using GEE models, controlling for confounders, both surgically and medically treated ectopic pregnancies were noted as independent risk factors for preterm delivery in the subsequent pregnancies. Maternal history of surgically treated ectopic pregnancy was also independently associated with cesarean delivery. Offspring to mothers with previous ectopic pregnancy had comparable rates of long-term neurological morbidity. In the Cox proportional hazards model, controlling for confounders, being born to a mother with a history of previous ectopic pregnancy was not found to be independently associated with long-term neurological morbidity of offspring. CONCLUSIONS: Maternal history of ectopic pregnancy is independently associated with preterm delivery. However, offspring of mothers with a history of ectopic pregnancy are not at an increased risk for long-term neurological morbidity.