Perinatal Outcomes in Appropriately Grown Monochorionic Diamniotic Twins With Intermittent Absent and Reversed End-Diastolic Umbilical Artery Flow Compared to Selective Fetal Growth Restriction Type III.

Objectives: Umbilical artery Doppler intermittent absent and reversed end-diastolic flow (iAREDF) is associated with increased perinatal morbidity and mortality in monochorionic twins with selective fetal growth restriction. The clinical significance of umbilical artery iAREDF in appropriately grown monochorionic twins is not well described.

Methods: This is a single-institution retrospective cohort study describing characteristics and outcomes of monochorionic diamniotic twins with appropriate for gestational age growth and umbilical artery iAREDF in comparison to monochorionic diamniotic twins with selective fetal growth restriction and iAREDF, or sFGR type III.

Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism.

Alzheimer's disease protective allele of modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication.

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms remain largely unknown. For a strong AD-associated locus near (), we tied an AD protective allele to a role of neuronal CLU in promoting neuron excitability through lipid-mediated neuron-glia communication.

Comparison of Serial Amnioinfusion Strategies for Isolated Early-Onset Fetal Renal Anhydramnios.

Introduction: The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early-onset fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches.

Methods: A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Anhydramnios Fetal Therapy (RAFT) trial.

Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease?

In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep.

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models.

Peripheral tissues become disrupted in Alzheimer's Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aβ42 and Tau, in neurons impacts the periphery is lacking. Using , a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer's Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human Aβ42 or Tau.

Autolysosomal exocytosis of lipids protect neurons from ferroptosis.

During oxidative stress neurons release lipids that are internalized by glia. Defects in this coordinated process play an important role in several neurodegenerative diseases. Yet, the mechanisms of lipid release and its consequences on neuronal health are unclear.

PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells.

Treatment-resistant glioma stem cells are thought to propagate and drive growth of malignant gliomas, but their markers and our ability to target them specifically are not well understood. We demonstrate that podoplanin (PDPN) expression is an independent prognostic marker in gliomas across multiple independent patient cohorts comprising both high- and low-grade gliomas. Knockdown of PDPN radiosensitized glioma cell lines and glioma-stem-like cells (GSCs).

Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's disease-associated genes.

A growing list of Alzheimer's disease (AD) genetic risk factors is being identified, but the contribution of each variant to disease mechanism remains largely unknown. We have previously shown that elevated levels of reactive oxygen species (ROS) induces lipid synthesis in neurons leading to the sequestration of peroxidated lipids in glial lipid droplets (LD), delaying neurotoxicity. This neuron-to-glia lipid transport is APOD/E-dependent.

Recent insights into the role of glia and oxidative stress in Alzheimer's disease gained from Drosophila.

Here, we discuss findings made using Drosophila on Alzheimer's disease (AD) risk and progression. Recent studies have investigated the mechanisms underlying glia-mediated neuroprotection in AD. First, we discuss a novel mechanism of glial lipid droplet formation that occurs in response to elevated reactive oxygen species in neurons.

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila.

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila.

Evaluation of the Pubocervical Fascia With 3-Dimensional Endovaginal Ultrasonography and Correlation With Intraoperative Findings During Robotic Sacrocervicopexy.

Objectives: To evaluate the pubocervical fascia (PF) in patients with pelvic organ prolapse (POP) using 3-dimensonal endovaginal ultrasonography (EVUS) and to correlate the PF appearance with both pelvic examination and intraoperative findings during ultrasonographic robotic-assisted laparoscopic sacrocervicopexy and pubocervical fascia reconstruction (u-RALS-PFR).

Methods: A retrospective analysis was performed in 120 women with symptomatic POP. Preoperative evaluation was done using EVUS.

Ultrasonography and robotic-assisted laparoscopic sacrocervicopexy with pubocervical fascia reconstruction: comparison with standard technique.

The objective of this study was to evaluate our technique of ultrasonography and robotic-assisted sacrocervicopexy with pubocervical fascia reconstruction (u-RALS-PFR) versus standard robotic-assisted laparoscopic sacrocervicopexy (s-RALS) in the treatment of patients with symptomatic apical/anterior vaginal prolapse. A retrospective analysis was done using the data in two community hospitals. Thirty women presented with symptomatic vaginal apical prolapse and desired minimally invasive surgery (video): (a) standard robotic-assisted laparoscopic sacrocervicopexy (s-RALS) (n = 15) or (b) ultrasound and robotic-assisted sacrocervicopexy with pubocervical fascia reconstruction (u-RALS-PFR) (n = 15) were eligible to participate.

New Roles for Canonical Transcription Factors in Repeat Expansion Diseases.

The presence of microsatellite repeat expansions within genes is associated with >30 neurological diseases. Of interest, (GGGGCC)-repeats within C9orf72 are associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These expansions can be 100s to 1000s of units long.

Repeat-associated non-AUG (RAN) translation mechanisms are running into focus for GGGGCC-repeat associated ALS/FTD.

Many human diseases are associated with the expansion of repeat sequences within the genes. It has become clear that expressed disease transcripts bearing such long repeats can undergo translation, even in the absence of a canonical AUG start codon. Termed "RAN translation" for repeat associated non-AUG translation, this process is becoming increasingly prominent as a contributor to these disorders.

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD.

An expanded GGGGCC hexanucleotide of more than 30 repeats (termed (G4C2)) within C9orf72 is the most prominent mutation in familial frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) (termed C9). Through an unbiased large-scale screen of (G4C2)-expressing Drosophila we identify the CDC73/PAF1 complex (PAF1C), a transcriptional regulator of RNA polymerase II, as a suppressor of G4C2-associated toxicity when knocked-down. Depletion of PAF1C reduces RNA and GR dipeptide production from (G4C2) transgenes.

Drosophila Ref1/ALYREF regulates transcription and toxicity associated with ALS/FTD disease etiologies.

RNA-binding proteins (RBPs) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the underlying disease mechanisms remain unclear. In an unbiased screen in Drosophila for RBPs that genetically interact with TDP-43, we found that downregulation of the mRNA export factor Ref1 (fly orthologue to human ALYREF) mitigated TDP-43 induced toxicity. Further, Ref1 depletion also reduced toxicity caused by expression of the C9orf72 GGGGCC repeat expansion.

eIF4B and eIF4H mediate GR production from expanded G4C2 in a Drosophila model for C9orf72-associated ALS.

The discovery of an expanded (GGGGCC)n repeat (termed G4C2) within the first intron of C9orf72 in familial ALS/FTD has led to a number of studies showing that the aberrant expression of G4C2 RNA can produce toxic dipeptides through repeat-associated non-AUG (RAN-) translation. To reveal canonical translation factors that impact this process, an unbiased loss-of-function screen was performed in a G4C2 fly model that maintained the upstream intronic sequence of the human gene and contained a GFP tag in the GR reading frame. 11 of 48 translation factors were identified that impact production of the GR-GFP protein.

Robotic-assisted laparoscopic apical suspension: description of the spiral technique.

This video's objective was to describe our spiral technique and surgical steps of robotic-assisted laparoscopic apical suspension (RALAS) in the treatment of patients with symptomatic apical vaginal prolapse. A 70-year-old Caucasian woman, gravida 3, para 2 had symptomatic pelvic organ prolapse (POP) apical/anterior stage III. At pelvic ultrasound evaluation, the uterus was small and normal appearing of adnexa bilaterally.

ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts.

Background: Temozolomide (TMZ) is active against glioblastomas (GBM) in which the O6-methylguanine-DNA methyltransferase (MGMT) gene is silenced. However, even in responsive cases, its beneficial effect is undermined by the emergence of drug resistance. Here, we tested whether inhibition of poly (ADP-ribose) polymerase-1 and -2 (PARP) enhanced the effectiveness of TMZ.

Dipeptide repeat proteins activate a heat shock response found in C9ORF72-ALS/FTLD patients.

A hexanucleotide (GGGGCC) repeat expansion in C9ORF72 is the most common genetic contributor to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Reduced expression of the C9ORF72 gene product has been proposed as a potential contributor to disease pathogenesis. Additionally, repetitive RNAs and dipeptide repeat proteins (DPRs), such as poly-GR, can be produced by this hexanucleotide expansion that disrupt a number of cellular processes, potentially contributing to neural degeneration.

A gene expression signature predicts recurrence-free survival in meningioma.

Background: Meningioma is the most common primary brain tumor and has a variable risk of local recurrence. While World Health Organization (WHO) grade generally correlates with recurrence, there is substantial within-grade variation of recurrence risk. Current risk stratification does not accurately predict which patients are likely to benefit from adjuvant radiation therapy (RT).