Abstract For a dilation and evacuation (D&E) procedure, the cervix must be dilated sufficiently to allow passage of operative instruments and products of conception without injuring the uterus or ...cervical canal. Preoperative preparation of the cervix reduces the risk of cervical laceration and uterine perforation. The cervix may be prepared with osmotic dilators, pharmacologic agents or both. Dilapan-S™ and laminaria are the two osmotic dilators currently available in the United States. Laminaria tents, made from dehydrated seaweed, require 12–24 h to achieve maximum dilation. Dilapan-S™, made of synthetic hydrogel, achieves significant dilation within 4 h and is thus preferable for same-day procedures. A single set of one to several dilators is usually adequate for D&E before 20 weeks' gestation. Misoprostol, a prostaglandin E1 analogue, is sometimes used instead of osmotic dilators. It is generally regarded as safe and effective; however, misoprostol achieves less dilation than overnight osmotic tents. The literature supports same-day cervical preparation with misoprostol or Dilapan-S™ up to 18 weeks' gestation. As the evidence regarding alternative regimens increases, highly experienced D&E providers may consider same-day regimens at later gestations utilizing serial doses of misoprostol or a combination of osmotic and pharmacologic agents. Misoprostol use as an adjunct to overnight osmotic dilation is not significantly beneficial before 19 weeks' gestation. Limited data demonstrate the safety of misoprostol before D&E in patients with a prior cesarean delivery. Mifepristone, a progesterone receptor antagonist, is also effective for cervical preparation prior to D&E, although data to support its use are limited. The Society of Family Planning recommends preoperative cervical preparation to decrease the risk of complications when performing a D&E. Since no single protocol has been found to be superior in all situations, clinical judgment is warranted when selecting a method of cervical preparation.
Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate ...through amygdala-ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.
MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell ...persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3'UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size.
Clinical exome sequencing (CES) is rapidly becoming a common molecular diagnostic test for individuals with rare genetic disorders.
To report on initial clinical indications for CES referrals and ...molecular diagnostic rates for different indications and for different test types.
Clinical exome sequencing was performed on 814 consecutive patients with undiagnosed, suspected genetic conditions at the University of California, Los Angeles, Clinical Genomics Center between January 2012 and August 2014. Clinical exome sequencing was conducted as trio-CES (both parents and their affected child sequenced simultaneously) to effectively detect de novo and compound heterozygous variants or as proband-CES (only the affected individual sequenced) when parental samples were not available.
Clinical indications for CES requests, molecular diagnostic rates of CES overall and for phenotypic subgroups, and differences in molecular diagnostic rates between trio-CES and proband-CES.
Of the 814 cases, the overall molecular diagnosis rate was 26% (213 of 814; 95% CI, 23%-29%). The molecular diagnosis rate for trio-CES was 31% (127 of 410 cases; 95% CI, 27%-36%) and 22% (74 of 338 cases; 95% CI, 18%-27%) for proband-CES. In cases of developmental delay in children (<5 years, n = 138), the molecular diagnosis rate was 41% (45 of 109; 95% CI, 32%-51%) for trio-CES cases and 9% (2 of 23, 95% CI, 1%-28%) for proband-CES cases. The significantly higher diagnostic yield (P value = .002; odds ratio, 7.4 95% CI, 1.6-33.1) of trio-CES was due to the identification of de novo and compound heterozygous variants.
In this sample of patients with undiagnosed, suspected genetic conditions, trio-CES was associated with higher molecular diagnostic yield than proband-CES or traditional molecular diagnostic methods. Additional studies designed to validate these findings and to explore the effect of this approach on clinical and economic outcomes are warranted.
Brain tumor (BT) patients often experience reduced cognitive abilities and disrupted adaptive functioning before and after treatment. An innovative approach to understanding the underlying brain ...networks associated with these outcomes has been to study the brain's functional connectivity (FC), the spatially distributed and temporally correlated activity throughout the brain, and how it can be affected by a tumor. The present review synthesized the extant BT FC literature that utilizes functional magnetic resonance imaging to study FC strength of commonly observed networks during rest and task. A systematic review of English articles using PubMed was conducted. Search terms included brain tumor OR glioma AND functional connectivity, independent component analysis, ICA, psychophysiological interaction, OR PPI. Studies in which participants were diagnosed with BTs as adults that evaluated specific networks of interest using independent component analysis or seed-based component analysis were included. Twenty-five studies met inclusion criteria. BT patients often presented with decreases in FC strength within well-established networks and increases in atypical FC patterns. Network differences were tumor adjacent and distal, and left hemisphere tumors generally had a greater impact on FC. FC alterations often correlated with behavioral or cognitive outcomes when assessed. Overall, BTs appear to lead to various alterations in FC across different functional networks, and the most common change is a decrease in expected FC strength. More longitudinal studies are needed to determine the time course of network alterations across treatment and recovery, the role of medical treatments in BT survivors' FC, and the potential of FC patterns as biomarkers of cognitive outcomes.
For a dilation and evacuation (D&E) procedure, the cervix must be dilated sufficiently to allow passage of operative instruments and products of conception without injuring the uterus or cervical ...canal. Preoperative preparation of the cervix reduces the risk of cervical laceration and uterine perforation. The cervix may be prepared with osmotic dilators, pharmacologic agents or both. Dilapan-S™ and laminaria are the two osmotic dilators currently available in the United States. Laminaria tents, made from dehydrated seaweed, require 12-24 h to achieve maximum dilation. Dilapan-S™, made of synthetic hydrogel, achieves significant dilation within 4 h and is thus preferable for same-day procedures. A single set of one to several dilators is usually adequate for D&E before 20 weeks' gestation. Misoprostol, a prostaglandin E1 analogue, is sometimes used instead of osmotic dilators. It is generally regarded as safe and effective; however, misoprostol achieves less dilation than overnight osmotic tents. The literature supports same-day cervical preparation with misoprostol or Dilapan-S™ up to 18 weeks' gestation. As the evidence regarding alternative regimens increases, highly experienced D&E providers may consider same-day regimens at later gestations utilizing serial doses of misoprostol or a combination of osmotic and pharmacologic agents. Misoprostol use as an adjunct to overnight osmotic dilation is not significantly beneficial before 19 weeks' gestation. Limited data demonstrate the safety of misoprostol before D&E in patients with a prior cesarean delivery. Mifepristone, a progesterone receptor antagonist, is also effective for cervical preparation prior to D&E, although data to support its use are limited. The Society of Family Planning recommends preoperative cervical preparation to decrease the risk of complications when performing a D&E. Since no single protocol has been found to be superior in all situations, clinical judgment is warranted when selecting a method of cervical preparation.
Anatomic assessment of the medial upper arm to identify potential sites for insertion of the etonogestrel (ENG) implant.
Forty female cadaveric arms were dissected. Two rows of 1×2-cm dissection ...windows were created in the inner arm overlying the triceps approximately 2–3 and 4–5 cm posterior to the bicipital sulcus (sulcus). The primary window was 8–10 cm proximal to the medial epicondyle and approximately 2–3 cm posterior to the sulcus. Neurovascular structures within each window were identified. The entire medial upper arm was dissected to visualize underlying structures.
Mean age (± SD) of cadavers at death was 72.0±11.0 years. Arm measurements at the primary window were circumference 28.2±4.8 cm range: 21–41, skin thickness 0.6±0.2 mm 0.3–1.0 and subcutaneous tissue thickness: 12.3±4.9 mm 4.7–21. The basilic vein and the medial brachial cutaneous, ulnar and medial antebrachial cutaneous nerves were located in 40%, 58%, 40% and 18% of the primary windows, respectively. No major neurovascular structures were located 3–5 cm posterior to the sulcus. More neurovascular structures were identified overlying the biceps than triceps. Elbow flexion with the hand underneath the head displaced the ulnar nerve anteriorly towards the sulcus.
As no major neurovascular structures were identified overlying the triceps 8–10 cm proximal to the medial epicondyle and 3–5 cm posterior to the sulcus, ENG implant insertion at this location may minimize risk of injury associated with improper deep insertion. Elbow flexion deflects the ulnar nerve away from this area and may further decrease risk of injury secondary to inadvertent deep insertion.
Although a limited cadaver study, this anatomic assessment provides rationale for insertion of the ENG implant overlying the triceps 8–10 cm proximal to the medial epicondyle and 3–5 cm posterior to the sulcus. This area is theoretically safer for insertion of the ENG implant than areas of the inner arm where major neurovascular structures are commonly located.
Childhood brain tumors and related treatments disrupt the developing brain and have a cascading impact on core cognitive skills and intellectual (intelligence quotient IQ) and academic achievement ...outcomes. Theoretical models for this cascade have been developed based on the literature, but no studies thus far have empirically evaluated the models. The current study aimed to empirically test the two extant models and generate a new data-driven model of the relationships among neurodevelopmental risk factors, core cognitive skills (i.e., processing speed, attention span, working memory), and IQ and achievement outcomes. Fifty-seven adult survivors of childhood brain tumors and fifty-seven demographically matched neurotypical individuals were included in the current study. The average age at brain tumor diagnosis was 8 years, and the average time since diagnosis was 17 years. Three a priori path models tested the hypothesized relationships among variables. Results of the path analyses revealed that the hybrid model best fit the data for both survivors and controls based on all statistical criteria. For survivors, processing speed was the core cognitive skill most widely associated with neurodevelopmental risk factors and outcomes. However, working memory and attention span also had unique contributions to IQ and academic achievement. Processing speed appears to be the central cognitive skill that disrupts the other core cognitive skills of attention span and working memory, and all three make a unique contribution to IQ and academic achievement. This is best demonstrated by a novel neurodevelopmental model that combines components of two earlier untested theoretical models.
The Reliable Digit Span (RDS) is a performance validity test (PVT) used widely within non-clinical samples, but its utility is in question in clinical groups with cognitive impairment. To ...investigate, RDS scores were calculated and correlated with the Neurological Predictor Scale, an informant-reported Activities of Daily Living score, and a proxy measure of intelligence (Vocabulary) for 83 adult survivors of childhood brain tumors and 105 healthy controls. Analyses were covaried for age at examination. Participants were divided into passing and failing groups at each RDS cutoff, and ANCOVAs for each of the three variables of interest covaried for age at the examination were run. RDS was correlated with all three variables of interest in survivors but only Vocabulary in controls. At the ≤7 cutoff, passing and failing survivors demonstrated significant differences across all variables of interest, while passing and failing controls differed only on Vocabulary. Differences were also found between passing and failing survivors at lower cutoffs. RDS is related to and likely impacted by various neurological and cognitive challenges faced by brain tumor survivors. Using the standard RDS cutoff of ≤7 may result in inaccurate interpretation of valid performance in this population; therefore, the use of other PVTs is recommended.
Hearing loss is a common and complex condition that can occur at any age, can be inherited or acquired, and is associated with a remarkably wide array of etiologies. The diverse causes of hearing ...loss, combined with the highly variable and often overlapping presentations of different forms of hearing loss, challenge the ability of traditional clinical evaluations to arrive at an etiologic diagnosis for many deaf and hard-of-hearing individuals. However, identifying the etiology of a hearing loss may affect clinical management, improve prognostic accuracy, and refine genetic counseling and assessment of the likelihood of recurrence for relatives of deaf and hard-of-hearing individuals. Linguistic and cultural identities associated with being deaf or hard of hearing can complicate access to and the effectiveness of clinical care. These concerns can be minimized when genetic and other health-care services are provided in a linguistically and culturally sensitive manner. This guideline offers information about the frequency, causes, and presentations of hearing loss and suggests approaches to the clinical evaluation of deaf and hard-of-hearing individuals aimed at identifying an etiologic diagnosis and providing informative and effective patient education and genetic counseling.
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