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The choroid plexus (CP) is a highly vascularized structure located in the ventricles that forms the blood-CSF barrier (BCSFB) and separates the blood from the cerebrospinal fluid (CSF). In addition to its role as a physical barrier, the CP functions in CSF secretion, transport of nutrients into the central nervous system (CNS) and a gated point of entry of circulating immune cells into the CNS. Aging and neurodegeneration have been reported to affect CP morphology and function and increase protein leakage from blood to the CSF. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both upper and lower motor neuron loss, as well as altered proteomic and metabolomic signatures in the CSF. The role of the BCSFB and the CP in ALS is unknown. Here we describe a transcriptomic and ultrastructural analysis of BCSFB and CP alterations in human postmortem tissues from ALS and non-neurologic disease controls. ALS-CP exhibited widespread disruptions in tight junctional components of the CP epithelial layer and vascular integrity. In addition, we detected loss of pericytes around ALS blood vessels, accompanied by activation of platelet aggregation markers vWF and Fibrinogen, reminiscent of vascular injury. To investigate the immune component of ALS-CP, we conducted a comprehensive analysis of cytokines and chemokine panels in CP lysates and found a significant down-regulation of M-CSF and V-CAM1 in ALS, as well as up-regulation of VEGF-A protein. This phenotype was accompanied by an infiltration of MERTK positive macrophages into the parenchyma of the ALS-CP when compared to controls. Taken together, we demonstrate widespread structural and functional disruptions of the BCSFB in human ALS increasing our understanding of the disease pathology and identifying potential new targets for ALS therapeutic development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Determine the prevalence of substance use among pregnant women in five diverse communities utilizing the 4P's Plus screen for alcohol, tobacco, and other drug use. STUDY DESIGN: Pregnant women enrolled in prenatal care clinics in five communities were screened for substance use with the 4P's Plus. Those women with a positive screen underwent an assessment for substance use through a follow-up structured clinical interview conducted at the same prenatal visit. RESULTS: Among 7818 women in five communities, 2555 (32.7%) had a positive screen for substance use in pregnancy. Four of the communities conducted a follow-up assessment on all women with a positive screen (n = 1548). Among these women, 717 (15% of the total population) had continued use after learning of the pregnancy. Overall, 21% of the pregnant women used alcohol prior to recognition of the pregnancy, and 11% continued use after knowledge of the pregnancy. Among the 512 women who continued to use alcohol, 2% were drinking daily, 7% were drinking 3 to 6 days per week, 27% were drinking 1 to 2 days per week, and 63% were drinking less than 1 day per week. The rates of marijuana use and other illicit drug use among the women were 7 and 2%, respectively, prior to knowledge of pregnancy and dropped to 3 and 1% after learning of the pregnancy. CONCLUSION: The 4P's Plus identifies not only those pregnant women whose drinking or drug use is at a high enough level to impair daily functioning, but provides an opportunity for early intervention for the much larger group of women whose pregnancies are at risk from relatively small amounts of substance use. [ABSTRACT FROM AUTHOR]

This article examines FIMR in relationship to two other maternal and child health mortality reviews-child fatality review (CFR) and maternal mortality review (MMR), and explores how their approaches to reviewing deaths can complement one another. Identifying opportunities for collaboration among these case review methodologies may lead to greater efficiencies at the local and state levels and strengthen the case review approach as a public health tool for improving maternal and child health outcomes. To enable comparative analysis, a table was constructed that identifies the purpose, structure, and process features of each case review approach. This was followed by an examination of two possible ways to improve maternal and child mortality review processes in states: 1) better coordination; and 2) improving each individual process through adapting and adopting promising practices from the others. A discussion is also provided of the state Title V role in facilitating both the coordination of reviews and the process of sharing best practices. Given the similarities that exist among the three MCH mortality reviews, it is important to view each review as one component of a larger system of maternal and child health death reviews. Implementing widely the recommendations generated by these reviews may increase the likelihood of improvements in services and systems on behalf of women and children. [ABSTRACT FROM AUTHOR]

Objective: To motivate prenatal care staff in public and private settings to universally screen for risk of alcohol and drug use and to conduct a brief intervention with follow-up referral when appropriate during a routine office visit. Methods: The ASAP Project methods were engagement of site staff; staff training; self-administered questionnaires embedded with a relational and broad catch screening tool; a brief intervention protocol; unique clinical decision tree/protocols for each site; identification of treatment and referral resources; and ongoing technical assistance and consultation. Sites were located in four regions of the state and included four community health centers, a network of multi-specialty private practices and a teaching hospital. Results: Across 16 sites, 118 prenatal staff were trained on use of the screening tool and 175 staff on the brief intervention. The ASAP Project resulted in 95% of pregnant women being screened for alcohol use and 77% of those screening positive for at least one risk factor receiving a brief intervention during a routine office visit. Conclusions: Screening and brief interventions for alcohol use can be delivered effectively within a routine prenatal care visit by prenatal staff by utilizing and building on existing office systems with practice staff, screening for any use not only at risk use, providing training with skills building sessions and information delivered by physicians, offering easy-to-access community treatment resources, and providing ongoing technical assistance. [ABSTRACT FROM AUTHOR]