White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery.repair | oligodendrocyte progenitor cell | oligodendrocyte | subventricular zone | astrocyte I schemic stroke in the adult brain occurs in two basic forms. Occlusion of large brain arteries produces stroke that spans brain areas, including gray matter (cortex, striatum) and white matter regions. Stroke in small brain vessels often occurs only in subcortical white matter regions, and these infarcts account for up to 25% of all stroke. The incidence of white matter stroke is age-associated and is the second leading cause of dementia (1-3). The resulting infarcts are distinct from large artery stroke, not only in cause and location but also in progressive accumulation over time (1,3,4). Ischemic regions after white matter stroke grow, with progression of the damage even in the controlled conditions of a clinical trial (5). Importantly, the presence of white matter ischemic lesions closely correlates with abnormalities in cognition, balance, and gait and carries an increased risk of death (6, 7).Despite such clinical importance, white matter repair after white matter stroke is still relatively unknown, which is in part because most basic science studies of stroke focus on large artery infarcts, such as middle cerebral artery occlusions. Most of what is known about white matter repair is derived from studies in inflammatory or toxic injuries of white matter, such as multiple sclerosis (MS). In these nonstroke...

Objectives Sexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine. Methods Between November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy. Results In 242 women (median age 29 years [IQR = 24–34], median gestation 19 weeks [IQR = 14–24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02–3.67), being unmarried or not cohabiting with the fetus’ father (aOR = 2.19; 95% CI = 1.16–4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08–20.95) were associated with STI diagnosis. Conclusion We found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy.

Subcortical white matter stroke is a common stroke subtype. White matter stroke stimulates adjacent oligodendrocyte progenitor cells (OPCs) to divide and migrate to the lesion, but stroke OPCs have only a limited differentiation into mature oligodendrocytes. To understand the molecular systems that are active in OPC responses in white matter stroke, OPCs were virally labeled and laser-captured in the region of partial damage adjacent to the infarct in male mice. RNAseq indicates two distinct OPC transcriptomes associated with the proliferative and limited-regeneration phases of OPCs after stroke. Molecular pathways related to nuclear receptor activation, ECM turnover, and lipid biosynthesis are activated during proliferative OPC phases after stroke; inflammatory and growth factor signaling is activated in the later stage of limited OPC differentiation. Within ECM proteins, Matrilin-2 is induced early after stroke and then rapidly downregulated. Prediction of upstream regulators of the OPC stroke transcriptome identifies several candidate molecules, including Inhibin A-a negative regulator of Matrilin-2. Inhibin A is induced in reactive astrocytes after stroke, including in humans. In functional assays, Matrilin-2 induces OPC differentiation, and Inhibin A inhibits OPC Matrilin-2 expression and inhibits OPC differentiation. In vivo, Matrilin-2 promotes motor recovery after white matter stroke, and promotes OPC differentiation and ultrastructural evidence of remyelination. These studies show that white matter stroke induces an initial proliferative and reparative response in OPCs, but this is blocked by a local cellular niche where reactive astrocytes secrete Inhibin A, downregulating Matrilin-2 and blocking myelin repair and recovery.

Pregnant and postpartum women in Southern Africa are at increased risk of HIV infection. Pre-exposure prophylaxis in pregnancy and postpartum periods could significantly reduce the risk of HIV acquisition and transmission in pregnancy. Participants at a community health clinic in Cape Town completed a survey about demographic and sexual risk behaviors, and prior knowledge of pre-exposure prophylaxis. We evaluated factors associated with knowledge of pre-exposure prophylaxis using multivariable logistic regression. We enrolled 50 pregnant and 37 postpartum women, of whom 51% were HIV-uninfected. Twenty-nine (33%) knew about pre-exposure prophylaxis, most from their healthcare provider (69%). Older age (adjusted odds ratio [aOR]/year = 1.09, 95% CI = 1.00–1.19), unintended pregnancy (aOR = 3.36, 95% CI = 1.06–12.12), and more than one sex partner in the last year (aOR = 5.31, 95% CI = 1.12–30.07) were associated with pre-exposure prophylaxis knowledge. Our study identified low levels of pre-exposure prophylaxis knowledge in pregnant and breastfeeding women, but increased knowledge in higher risk women. These results provide guidance to develop interventions to increase pre-exposure prophylaxis knowledge and uptake.

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Background:Staphylococcus aureus is a common cause of healthcare associated infections and is associated with high mortality. S. aureus colonization of skin and mucosa contributes to its pathogenesis. Universal S. aureus decolonization reduces methicillin-resistant S. aureus (MRSA) and other bloodstream infections among ICU patients. However, universal decolonization in acute-care settings has not shown a similar benefit. We describe a targeted decolonization protocol implemented at a large academic hospital across acute-care and intensive care settings. We assessed the impact of decolonization on S. aureus–related infections. Methods: Adults admitted in 2018–2019 to the medicine, oncology, transplant, and ICU services were screened for S. aureus colonization using nasal swabs for MRSA/MSSA by culture. Those with S. aureus detected underwent decolonization with 5 days of chlorhexidine 2% baths and mupirocin intranasal ointment. Decolonization was considered complete if given for 5 days. The primary outcome was S. aureus invasive infection from hospital day 3 until discharge, defined by positive clinical cultures from sterile sites. Secondary outcomes included 30-day readmission and 30-day mortality. The control population was patients with negative MRSA/MSSA nasal screening in the same hospital units. Results: In total, 4,465 (23%) of 19,065 screening tests were positive for MSSA (75%) or MRSA (25%). The median age was 69 years (IQR, 56–80), and the median length of stay (LOS) was 6 days (IQR, 4–10). Among patients with LOS ≥3 days, 541 (16%) completed decolonization and 2,161 (64%) received no decolonization. The rate of complete decolonization increased to 35% among those with LOS ≥ 7 days. In total, 802 screened patients developed invasive S. aureus infections. Of 4,437 colonized patients, 536 (12%) had invasive infections, compared with 265 (2.1%) invasive infections in 12,917 noncolonized patients. Among patients with S. aureus colonization, 24% of decolonized patients developed invasive infection and 13% of patients who were not decolonized developed invasive infection. Rates of 30-day readmission and mortality were 28% and 10%, respectively, among fully decolonized patients, versus 20% and 6.6% among those receiving no decolonization. Conclusions: These data provide an assessment of the efficacy of a targeted screening and decolonization program. Although decolonization did not reduce rates of invasive infection or secondary outcomes, further analysis is needed. Patients with longer lengths of stay are more likely to receive full decolonization but are also at higher risk of invasive infection, which may contribute to our unexpected results.Funding: NoneDisclosures: None

Background Staphylococcus aureus is a common cause of healthcare associated infections and is associated with high mortality. Universal S. aureus decolonization reduces methicillin-resistant S. aureus (MRSA) and other bloodstream infections among ICU patients. However, universal decolonization in acute care settings has not shown a similar benefit. We describe a screening and targeted decolonization protocol implemented at an academic hospital across acute and intensive care settings. The goal of this study was to assess the impact of decolonization on rates of S. aureus invasive infections. Methods Adult Medicine, Oncology, Transplant, and ICU patients were screened by nasal swab for S. aureus colonization on admission and change in level of care. Colonized patients received 5 days of chlorhexidine 2% applied to the body and mupirocin for the nares. We compared decolonized patients with patients who received no decolonization. The primary outcome was S. aureus invasive infection from hospital day 5 until discharge, defined by positive cultures from sterile sites. Secondary outcomes included 30-day readmission and 30-day mortality. Results Between 2018-2020, 3,835 (23%) out of 16,467 hospitalized patients screened positive for MSSA (74%) or MRSA (26%). Among colonized patients, median age was 67 years (interquartile range [IQR] 54-79) and median LOS was 6 days (IQR 4-11). Among patients with LOS ≥ 5 days, 977 (37%) received decolonization. There were 122 invasive infections, 56 (46%) occurring in patients who received decolonization. Wound infections were most common (28; 23%), followed by bacteremia (27; 22%). In multivariate regression analysis controlling for confounding factors including comorbidities and length of stay, decolonization was not significantly associated with incident invasive infections (p = 0.395). Conclusion We report on a S. aureus screening and targeted decolonization program; our initial analyses do not demonstrate an association between decolonization and reduced invasive S. aureus infections. Further investigations will examine subsets of high-risk patients and transmission events to assess if specific populations may benefit from this program. Disclosures All Authors: No reported disclosures.