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Background Hypertonic saline (HS) is commonly prescribed for children with cystic fibrosis (CF) despite the absence of strong data indicating clinical efficacy in a population with mild lung disease. We hypothesized that HS treatment would result in a sustained improvement in mucociliary clearance (MCC) in children with CF who had minimal lung disease, thus providing evidence for a biologically relevant effect that also may be associated with clinical improvements. Methods We performed a randomized, placebo controlled, double blind study of 6% versus 0.12% sodium chloride, delivered three-times daily with an eFlow nebulizer for 4 weeks. MCC was measured using gamma scintigraphy at baseline, 2-hours after the first study treatment, and ~12-hours after the final dose (at day 28). Spirometry, respiratory symptoms (CFQ-R), and safety were also assessed. Results Study treatments were generally well tolerated and safe. HS (6% sodium chloride) resulted in a significant, sustained improvement from baseline in whole lung clearance after 4 weeks of therapy (p = 0.014), despite absence of a prolonged single-dose effect after the initial dose. This sustained change (12 hrs after prior dose) was significantly greater when compared to placebo (0.12% sodium chloride) treatment (p = 0.016). Improvements in spirometry with HS did not reach statistical significance but correlated with MCC changes. Conclusions The observed sustained improvement in MCC with HS suggests that this treatment may yield health benefits, even in relatively mildly affected children with CF. Highlighting this physiologic finding is important due to the lack of meaningful, validated endpoints in this population.

International audience; Primary ciliary dyskinesia (PCD) is a genetic disorder in which impaired ciliary function leads to chronic airway disease. Exome sequencing of a PCD subject identified an apparent homozygous frameshift variant, c.887_890delTAAG (p.Val296Glyfs∗13), in exon 5; this frameshift introduces a stop codon in amino acid 308 of the growth arrest-specific protein 2-like 2 (GAS2L2). Further genetic screening of unrelated PCD subjects identified a second proband with a compound heterozygous variant carrying the identical frameshift variant and a large deletion (c.867_∗343+1207del; p.?) starting in exon 5. Both individuals had clinical features of PCD but normal ciliary axoneme structure. In this research, using human nasal cells, mouse models, and X.laevis embryos, we show that GAS2L2 is abundant at the apical surface of ciliated cells, where it localizes with basal bodies, basal feet, rootlets, and actin filaments. Cultured GAS2L2-deficient nasal epithelial cells from one of the affected individuals showed defects in ciliary orientation and had an asynchronous and hyperkinetic (GAS2L2-deficient = 19.8 Hz versus control = 15.8 Hz) ciliary-beat pattern. These results were recapitulated in Gas2l2-/- mouse tracheal epithelial cell (mTEC) cultures and in X. laevis embryos treated with Gas2l2 morpholinos. In mice, the absence of Gas2l2 caused neonatal death, and the conditional deletion of Gas2l2 impaired mucociliary clearance (MCC) and led to mucus accumulation. These results show that a pathogenic variant in GAS2L2 causes a genetic defect in ciliary orientation and impairs MCC and results in PCD

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.

Background Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI. Methods We assessed the effects of a single dose of Mucinex ® 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8–12 for each cohort). Results We found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo. Conclusions There was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. ClinicalTrials.gov Identifier: NCT01114581

The objective of this study was to determine if fetal-maternal cell trafficking is affected by maternal immune competence and/or parental background strain using fluorescence-activated cell sorting (FACS). In our experience the sensitivity of FACS allows for the detection of 5 fetal in 10(7) maternal cells and assessment of cell surface phenotype. Wild-type C57BL/6J (n=18), FVB/NJ (n=15), and immunodeficient B6129S7-Rag1(tm1Mom)/J (n=16) female mice were mated to C57BL/6J males homozygous for the green fluorescent protein (GFP) transgene. Single cell suspensions of maternal lung, liver, spleen, bone marrow, and blood were analyzed between late gestation (day e16-18) and 1 day post-partum for the number of GFP-positive fetal cells in relation to 10(7) maternal cells and the percentage of GFP-positive cells that expressed the surface markers CD11b, CD29, CD34, CD44, or CD105. The highest relative proportions of GFP-positive fetal cells were observed in maternal lungs and livers from immunocompetent allogenic females. Among congenic matings, fetal cell microchimerism was higher in immunodeficient compared with immunocompetent females. Maternal strain and strain differences between the mother and father statistically significantly affected both the numbers of fetal cells and the relative distribution of cell types in maternal organs. The highest relative proportion of fetal cells was observed in allogenic matings with immunocompetent females. Since allogenic matings are more similar to those that occur in humans, future studies using animal models of microchimerism should consider incorporating this type of experimental design.

Neonates are exposed to elevated levels of reactive oxygen species as they transition from a hypoxic intrauterine to a normoxic extrauterine environment at birth. This increased oxidative stress is associated with neonatal morbidity. Current antioxidant supplementation treatment strategies have yet to translate into improved neonatal outcomes. Our understanding of a newborn's intricate redox balance, particularly at the genomic level, remains limited. Here, we performed genomic microarray analyses (approximately 14,500 genes) on extracted mRNA from umbilical cord whole blood at term gestation (n=10). Bioinformatic analyses identified 282 genes (2.0%) that were consistently present within the highest quintile of expressed genes. These genes were highly associated with oxidant stress and included superoxide dismutase 1, catalase, peroxiredoxins, and uncoupling proteins. Pathway analyses identified statistically significantly overrepresented functional pathways including "oxidative stress," "oxidative stress response mediated by nuclear factor-erythroid 2-related factor," "hypoxia-inducible factor signaling," and "mitochondrial dysfunction" (p

To determine the kinetics of the short-term clearance of cell-free nucleic acids in maternal plasma, we conducted a prospective cohort study of 36 women who underwent first-trimester elective surgical termination. By using real-time polymerase chain reaction (PCR) amplification and measurement of the sex-determining region of the Y chromosome (SRY) gene (as a marker of fetal DNA), beta-hCG (a placental messenger RNA transcript), and glyceraldehyde phosphate dehydrogenase (GAPDH; as a marker of both total DNA and mitochondrial RNA), we found that cell-free nucleic acids in maternal plasma are not cleared within 90 minutes after the procedure, in contrast to the case of term delivery, in which levels decrease rapidly after birth.

The aim of this study was to examine fetal gene expression in maternal plasma after fetoscopic intervention for twin-twin transfusion syndrome or congenital diaphragmatic hernia.Twelve women with pregnancies that were complicated by twin-twin transfusion syndrome and 10 women carrying fetuses with congenital diaphragmatic hernia were sampled before and sequentially after treatment. Levels of glyceraldehyde-3-phosphate dehydrogenase, human placental lactogen, and gamma globin messenger RNA were measured by real-time reverse transcriptase polymerase chain reaction amplification.At all time points, glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels were higher in the congenital diaphragmatic hernia cases than in the twin-twin transfusion syndrome cases (P.05), but during the immediate postoperative observation period, there were no significant changes in glyceraldehyde-3-phosphate dehydrogenase, human placental lactogen, or gamma globin messenger RNA levels in individual patients or patients who were grouped by procedure.Fetoscopic intervention of complicated pregnancies does not affect circulating fetal messenger RNA levels, which is in contrast to earlier observations that circulating fetal DNA levels increase after laser ablation for twin-twin transfusion syndrome. Plasma glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels could be a potential novel biomarker for fetal trauma.

The effect of long acting beta(2)-adrenergic bronchodilators on impaired mucociliary clearance in chronic bronchitis is unknown. Using a radiolabeled aerosol (technetium-99m-labeled sulfur colloid) and gamma camera analysis, we measured the acute effect of salmeterol vs. placebo on mucociliary and cough clearance in mild-moderate chronic bronchitics (n = 14) over a 2h period. During the 1-1(1/2) h period of observation patients performed 60 controlled coughs on each study day. Average whole lung clearance through 1 and 2h after administration of salmeterol (42 microg) or placebo via metered dose inhaler (double-blinded, crossover design study) showed no significant difference between treatments. Similarly, for the specific period when cough was added to mucociliary clearance, there was no difference on whole lung clearance between treatments. However, when clearance from the peripheral region of the lung was assessed over the entire 2h period of observation, salmeterol provided a 30% enhancement of airway clearance compared to placebo, average peripheral 2h clearance (%) = 22 +/- 9 vs. 17 +/- 10 for salmeterol vs. placebo (P = 0.05 by paired analysis). Thus, in addition to its bronchodilating effects, salmeterol acutely enhances peripheral airway clearance of secretions in mild-moderate chronic bronchitis.

In humans, fetal cells enter the maternal circulation during all pregnancies and can persist for decades. Human studies, however, are often limited by the number of subjects and the availability of healthy and diseased tissues for analysis. We sought to develop a murine model to establish the natural history of fetal cell microchimerism in various maternal tissues during and after healthy pregnancies resulting from congenic and allogenic matings. We bred C57BL/6J and DBA/2J virgin female mice to C57BL/6J males transgenic for the enhanced green fluorescent protein (GFP), which shows autosomal dominant inheritance with complete penetrance and is under the control of a ubiquitous chicken beta-actin promoter and a cytomegalovirus enhancer. During pregnancy and at different times after delivery, female mice were sacrificed. Tissues were collected and the presence of the gfp transgene and GFP+ cells was assessed by real-time quantitative PCR and by immunofluorescence. During pregnancy, microchimerism was detected in all tissues from mice carrying GFP+ fetuses. Fetal cells were often mononuclear. The frequency of fetal cells in the lungs was significantly higher compared to other tissues. The level of microchimerism was also significantly higher in congenic compared to allogenic matings. After delivery, the frequency of fetal cells decreased and fetal cells were undetectable at 2 and 3 weeks after the first delivery. However, some mice that had three gestations had detectable fetal cells 3 weeks after their last delivery. Using sensitive methods of detection, we demonstrate that fetal cell microchimerism occurs during all murine pregnancies. We describe a useful model for the study of the consequences of this phenomenon.

Objective The purpose of this study was to determine whether cell-free fetal DNA is detectable in the cerebrospinal fluid of women during pregnancy and after delivery. Study design Cerebrospinal fluid was collected from 39 women who underwent an indicated spinal anesthesia procedure. Twenty-six samples were from women who carried at least 1 male fetus, and 13 samples were from women with only a female fetus. DNA was analyzed with the use of real-time polymerase chain reaction for DYS-1 (which represented male fetal DNA) and β-globin (which represented maternal and fetal DNA). Results β-Globin DNA was detected in all cerebrospinal samples. DYS-1 gene sequences were detected in 4 cerebrospinal fluid samples from women who had male fetuses (2 samples were from women who underwent cesarean delivery of singleton pregnancies, 1 sample was from a triplet pregnancy, and 1 sample was from a woman after delivery). No male DNA was detected in the cerebrospinal fluid of women who carried female fetuses. Conclusion Male fetal cells and/or cell-free fetal DNA is detectable in the cerebrospinal fluid of some pregnant women or some women after delivery.

Objectives On the basis of reports of maternal cells being detected in the umbilical cord blood of newborn infants, we tested the hypothesis that maternal cells can migrate out of the circulation into newborn tissues. Study design We studied autopsy material from 4 newborn infants who never received a blood transfusion and died during the first week of life. The study subjects' diagnoses were trisomy 21 with nonimmune hydrops, 46,XY, 4q+ with multiple congenital anomalies, Potter syndrome, and congenital ichthyosis. Fluorescence in situ hybridization analysis with X and Y chromosome–specific probes was performed on sections of paraffin-embedded tissue, including liver, spleen, thymus, thyroid, and skin. Results Female cells, as defined by the presence of intact nuclei with two X chromosome signals, were detected in multiple tissue types from all 4 male neonates. The number of female cells varied from 3 to 45 per slide. Conclusions Maternal cells enter the fetal circulation and are capable of migration to fetal and neonatal organs. This is of importance with regard to potential consequences of umbilical cord blood transplantation and postnatal development of autoimmune disease. (J Pediatr 2003;142:31-5)

In this paper we determined whether the frequencies of translocations and insertions are proportional to chromosome size in peripheral blood lymphocytes from Chernobyl nuclear accident clean-up workers and healthy unexposed control subjects. The frequency of aberrations among chromosomes 1, 2 and 4 in both groups was found to be significantly different from the distribution expected on the basis of chromosome size, although the difference was only marginally significant in controls. We also determined whether differences exist in aberration frequencies measured by two scoring systems: the classical method, where reciprocal exchanges are scored as one event, and PAINT, where each break junction is scored as a single event. The two scoring systems gave highly correlated results which yielded an interpretable arithmetic relationship between frequency measurements using the two systems. Approximately 34% of all translocations were observed to be non-reciprocal, and cells bearing clones of abnormal cells were observed in 6 of 198 subjects (3.0%). Our results demonstrate that clones of abnormal cells and the presence of non-reciprocal translocations contribute to the non-proportional distribution of radiation-induced and spontaneous cytogenetic damage.

Objective To examine prevalence and correlates of trauma and posttraumatic stress disorder (PTSD) symptoms and diagnosis in older adolescents aged 16 through 22 years. Method The second cycle of a longitudinal epidemiological study in the Southeast included a semistructured interview assessing PTSD symptomatology administered to 490 adolescents. Results Approximately 3% of female subjects and 1% of male subjects satisfied the DSM-IV criteria for PTSD. Females reported more traumatic events than males, and black subjects reported more events than white subjects. Being female (odds ratio = 12.32), experiencing rape or child sexual abuse (odds ratio = 49.37), and witnessing an accident or medical emergency (odds ratio = 85.02) were associated with increased risk of PTSD. Conclusions While relatively few adolescents satisfy the criteria for PTSD, most subjects who experienced a traumatic event reported some PTSD symptoms. Specific types of traumatic events were associated with occurrence of PTSD.

This study compares body size perceptions and weight management practices of black and white adolescent females.Subjects were selected through a statewide, three-stage sampling procedure designed to provide a sample statistically representative of high school students in South Carolina.Participants included black (n = 1824) and white (n = 2256) females, 14-18 years of age, enrolled in South Carolina public high schools.Respondents were asked to assess their perceived body size as overweight, underweight, or about right. Self-reported weight management practices included dieting (reducing caloric intake), exercise, and other methods (including diet pills and vomiting). Chisquare analysis was used to assess the differences in body size perception and weight management behaviors. Polychotomous logistic regression was performed to examine association while controlling for socioeconomic status.Forty-one percent of the white adolescents and 29% of the black adolescents perceive themselves as overweight (p0.005). In the week prior to the survey, 28% of the white adolescents and 13% of the black adolescents reported dieting 34% of the while versus 23% of the black adolescents reported exercising to lose weight; and 45% of the white and 16% of the black students reported both dieting and exercising. Polychotomous logistic regression analysis showed that white adolescent girls were almost twice as likely to perceive themselves as overweight as black adolescent girls. The white students had 6.04 [95% confidence interval (CI), 1.77, 20.67] times the odds of using pills and vomiting and 3.76 (95% CI, 2.99, 4.72) times the odds of engaging in dieting and exercising as methods of weight management compared to the black students.These findings suggest that white adolescents are more likely to perceive themselves as overweight than black adolescents and are more likely to engage in unhealthy weight management practices than black adolescents.

Objective To investigate the frequency and phenomenology of clinical, subsyndromal, and subthreshold phobias in young adolescents. Method: A two-stage epidemiological study originally designed to investigate adolescent depression was conducted between 1986 and 1988 in the southeastern United States. In the first stage, a self-report depressive symptom questionnaire was administered to a community sample of 3,283 adolescents. In the diagnostic stage, the Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Children's Global Assessment Scale were administered to 487 mother-child pairs. Results Prevalence rates of clinical, subsyndromal, and subthreshold phobia were 2.3%, 14.5%, and 22.2%, respectively. One-year incidence rates were 0.4%, 8.0%, and 16.9%, with 43.0% of phobic subjects categorized at the same or a more severe level after a year. Females, blacks, subjects not living with both biological parents, and older adolescents were more likely to meet the diagnostic criteria for clinical phobia. The majority (77%) of subjects with clinical phobia experienced multiple phobias. Subsyndromal (52%) and subthreshold (74%) phobics were more likely to experience simple phobias only. Conclusions Phobic symptoms are relatively common at a moderate level and in the majority of adolescents are somewhat transitory in nature. Characteristic symptomatology and comorbidity may facilitate earlier identification of subjects at risk of persistent symptomatology and in need of treatment.

Objective To investigate the incidence, transition probabilities, and risk factors for obsessive-compulsive disorder (OCD) and subclinical OCD in adolescents. Method A two-stage epidemiological study originally designed to investigate depression was conducted between 1987 and 1989 in the southeastern United States. For the screening, a self-report depressive symptom questionnaire was administered to a community sample of 3,283 adolescents. In the diagnostic stage, the Schedule for Affective Disorders and Schizophrenia for School-Age Children was administered to 488 mother–child pairs. Baseline screening and diagnostic data from the first year the subject completed an interview and follow-up diagnostic data from subsequent years were used. Results The 1-year incidence rates of OCD and subclinical OCD were found to be 0.7% and 8.4%, respectively. Transition probabilities demonstrated a pattern of moving from more severe to less severe categories. Of those with baseline OCD, 17% had the diagnosis of OCD at follow-up; 62% moved to the referent group. Of those with baseline subclinical OCD, 1.5% had OCD at follow-up and 75% moved to the referent group. Black race (odds ratio [OR] = 23.38), age (OR = 4.02), desirable life events (OR = 0.78), undesirable life events (OR = 1.21), and socioeconomic status (OR not estimable) were significant predictors of incident OCD. Age (OR = 2.30), desirable life events (OR = 0.92), and undesirable life events (OR = 1.13) were significantly associated with incident subclinical OCD. Conclusion An initial diagnosis of subclinical OCD was not significantly predictive of a diagnosis of OCD at 1-year follow-up. The overall morbidity remained higher at follow-up in the baseline OCD group than in the baseline subclinical OCD group. The baseline subclinical OCD group was more dysfunctional at follow-up than was the baseline referent group. Further research concerning differences in symptomatology and impairment between OCD and subclinical OCD is warranted.

As part of a longitudinal study of depression and suicidal ideation in adolescents, a three-item suicide screen was administered to 1,073 students for 3 consecutive years starting at the beginning of the 7th or 8th grades. Each year over 70% of respondents reported no suicidal thoughts, and less than 5.5% attained high suicide ideation scores. Blacks and females had higher scores, respectively, than did whites and males. The individual students' suicide scores were less stable than the overall distributions with 1- and 2-year correlations reaching 0.35 and 0.28, respectively. Only one student received a high score all 3 years. The best predictors of a given year's suicide score was the previous years' depression scores. Gender, undesirable life events, family adaptability, and family cohesion were significant but less consistent predictors.

We examined two general measures of morbidity, musculoskeletal problems and respiratory symptoms, among participants of a 42 km race. We compared the morbidity experience of these participants to runners racing shorter distance events (5 km and 10 km) on the same day. Male marathon runners were almost twice as likely (and female marathon runners four times as likely) to report a lower extremity musculoskeletal problem in the month after the race as nonmarathon runners. Although adjusting for other factors did not change the crude odds ratio for either men or women, logistic regression results indicated that the strongest factor associated with lower extremity musculoskeletal problems in the month after the marathon was the report of a musculoskeletal problem in the year before the marathon. Neither male nor female marathon runners reported an excess of respiratory symptoms compared to those who ran shorter distances. However, a report of respiratory symptoms in the month before the race was statistically associated with respiratory symptoms in the month after the race. These results suggest that runners who have had lower extremity musculoskeletal problems in the year before, or those who have recently experienced respiratory symptoms, should use caution when preparing for and recovering from racing events.

This paper describes a basic investigation of possible non-response bias in a mail survey. We compare characteristics of responders and non-responders to a mail survey of health outcomes among participants of a longitudinal study of physical activity, physical fitness, and health. Results indicate that, at the first clinic visit, the responders were essentially the same as the non-responders on personal health history and laboratory measurements, while reporting significantly more family history of specific chronic diseases (cardiovascular disease, hypertension, stroke). The male responders were younger and reported more positive health behaviors as well as better weight and treadmill times at the first clinic visit. These results suggest that both response groups were equally healthy at entry, and that individuals who had family members with certain chronic conditions and who had positive health behaviors were more likely to respond (participate) in this health-related survey. Differences of this type could affect interpretation of future analyses. This work illustrates the importance of incorporating methods to examine non-response into any epidemiologic study.

amniotic fluid supernatant reveals major alterations in nervous and cardiovascular system gene expression LISA HUI, Heather Wick, Kenneth Moise, Anthony Johnson, Michael Belfort, Kirby Johnson, Diana Bianchi Tufts Medical Center, Mother Infant Research Institute, Boston, MA, Tufts University, Computer Science, Medford, MA, Baylor College of Medicine, Obstetrics and Gynecology, Houston, TX OBJECTIVE: To understand the molecular mechanisms underlying the recipient’s response to twin-twin transfusion syndrome (TTTS) and develop fetal biomarkers by performing functional genomic analysis of amniotic fluid supernatant (AFS). STUDY DESIGN: We have previously shown that AFS contains RNA from multiple fetal organs, including brain. This was a prospective study analyzing cell-free RNA transcripts in recipient AFS from women undergoing clinically-indicated laser surgery. Normal AFS was obtained from singleton fetuses undergoing genetic amniocentesis. The independent t test with the Benjamini-Hochberg correction was used to evaluate up-regulated genes in TTTS vs normal controls, and Quintero Stage III vs stage II cases. Functional analyses of the significantly up-regulated genes were performed with Ingenuity software. RESULTS: AFS samples from 8 recipient twins (4 Stage II and 4 Stage III, EGA 17-21 w) and 4 euploid controls (EGA 17-22 w) were included. Compared with controls, 811 genes were significantly upregulated in TTTS cases. The most statistically significant biological process that differed between cases and controls was nervous system development and function. There were 19 up-regulated nervous system genes in TTTS cases including microtubule-associated protein tau, a biomarker of adult neurodegeneration. Other important upregulated transcripts in TTTS were vascular endothelial growth factor 1 and angiotensin II receptor type 2. The most statistically significant up-regulated biological process in Stage III vs Stage II fetuses was cardiovascular disease. Among the 58 cardiovascular disease genes up-regulated in Stage III recipients were some specifically associated with hypertension and left ventricular dysfunction (TRPC4) and congenital pulmonary stenosis (NTRK3). CONCLUSION: Our study provides novel molecular evidence of the impact of TTTS on the developing nervous system. We also identified the cardiovascular genes specifically associated with Stage III vs Stage II disease. These results further our understanding of the pathophysiology of TTTS and provide potential prognostic fetal biomarkers. 424 Gender equality in fetal reduction (FR) patient decision preferences: major cultural change in the USA Mara Rosner, Stephanie Andriole, Avishai Alkalay, Rachel Greenbaum, Juliana Gebb, Mark Evans Montefiore Medical Center/Albert Einstein College of Medicine, Obstetrics & Gynecology and Women’s Health, Bronx, NY, Comprehensive Genetics, Genetic Counseling, New York, NY, Albert Einstein College of Medicine/ Montefiore Medical Center, Obstetrics and Gynecology & Women’s Health, Bronx, NY, Comprehensive Genetics, Ultrasound, New York, NY, Comprehensive Genetics & Mt. Sinai School of Medicine, Obstetrics & Gynecology, New York, NY OBJECTIVE: 20 years ago, a disproportionate % of gender preference requests for prenatal diagnosis, terminations, and reductions were from patients of ethnic groups that valued boys over girls. We refused to participate. As patient interest expanded to all ethnic groups and gender preference seemed to equalize, our bioethicist had us re-evaluate and incorporate patient preference. STUDY DESIGN: We prioritize FR decisions by: 1. documented major (M) anomaly; 2. suspicious or minor (m) findings; 3. if neither, we consider gender preference. We retrospectively reviewed patient choices in our last 400 CVS/FR cases starting with triplets or twins. Patients were categorized based on type of reduction (3i2, 3i1, or 2i1), presence or absence of M or m findings, and whether all fetuses were the same gender (SG) or a gender choice was possible. Higher order and non-CVS pregnancies were excluded. RESULTS: 178/321 (56%) had either M/m or SG. Of 3i2 with option, 71/79 reduced to M/F of which about 1/3rd had no preference. 1 chose MM and 7 chose FF. Most 3i1 included MZ twins for whom we reduced MZ in 33/35 cases. Of 20 3i1 with option, 10 chose M and 10 chose F. Of 44 2i1 with option, 20 chose M & 24 chose F. CONCLUSION: There has been a major shift in culture from a generation ago. Male preponderance has ended in the USA. The vast majority of our patients who reduced to 2 preferred one of each or had no preference. When reducing to 1, a non-significant trend towards female preference was found. In addition to identifying abnormalities, CVS prior to FR expands patient autonomy. Poster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org