Cholestasis impairs gut microbiota development and bile salt hydrolase activity in preterm neonates.

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing, in vitro BSH enzyme activity assays optimized for low biomass fecal samples, and quantitative mass spectrometry to measure the bile acid metabolome. In extremely preterm neonates, acquisition of the secondary bile acid biosynthesis pathway and BSH genes carried by Clostridium perfringens are the most prominent features of early microbiome development. Cholestasis interrupts this developmental pattern. BSH gene abundance and enzyme activity are profoundly reduced in cholestatic neonates, resulting in decreased quantities of unconjugated bile acids. UDCA restores total fecal bile acid levels in cholestatic neonates, but this is due to a 522-fold increase in fecal UDCA. A majority of bile acids in early development are atypical positional and stereo-isomers of bile acids. We report novel associations linking isomeric bile acids and BSH activity to neonatal growth trajectories. These data highlight deconjugation of bile acids as a key microbial function that is acquired in early neonatal development and impaired by cholestasis.

"Where do I even start?" Recommendations for faculty diversifying syllabi in ecology, evolution, and the life sciences.

Diversifying curricula is of increasing interest in higher education, including in ecology and evolution and allied fields. Yet, many educators may not know where to start. Here we provide a framework for meeting standard curriculum goals while enacting anti-racist and anti-colonial syllabi that is grounded in the development of a sustainable network of educators. In addition to highlighting this professional learning process and sharing the list of resources our group has developed, we provide suggestions to help educators highlight contributions of minoritized groups, explore multiple ways of knowing, and perform critical assessments of foundational views of life and environmental science fields. We further discuss the key classroom dynamics that affect the success of such anti-racist and anti-colonial initiatives. The retention and success of minoritized students in ecology and evolution depends on whether we address injustices in our fields. Our hope is that our fellow educators will use this paper to catalyze their own efforts to diversify their courses.

Efficacy of Group Exercise-Based Cancer Rehabilitation Delivered via Telehealth (TeleCaRe): Protocol for a Randomized Controlled Trial.

BACKGROUND: Access to rehabilitation to support cancer survivors to exercise is poor. Group exercise-based rehabilitation may be delivered remotely, but no trials have currently evaluated their efficacy. OBJECTIVE: We aimed to evaluate the efficacy of a group exercise-based cancer rehabilitation program delivered via telehealth compared to usual care for improving the quality of life of cancer survivors. METHODS: A parallel, assessor-blinded, pragmatic randomized controlled trial with embedded cost and qualitative analysis will be completed. In total, 116 cancer survivors will be recruited from a metropolitan health network in Melbourne, Victoria, Australia. The experimental group will attend an 8-week, twice-weekly, 60-minute exercise group session supervised via videoconferencing supplemented by a web-based home exercise program and information portal. The comparison group will receive usual care including standardized exercise advice and written information. Assessments will be completed at weeks 0 (baseline), 9 (post intervention), and 26 (follow-up). The primary outcome will be health-related quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at week 9. Secondary measures include walking capacity (6-minute walk test), physical activity (activPAL accelerometer), self-efficacy (Health Action Process Approach Questionnaire), and adverse events. Health service data including hospital length of stay, hospital readmissions, and emergency department presentations will be recorded. Semistructured interviews will be completed within an interpretive description framework to explore the patient experience. The primary outcome will be analyzed using linear mixed effects models. A cost-effectiveness analysis will also be performed. RESULTS: The trial commenced in April 2022. As of June 2022, we enrolled 14 participants. CONCLUSIONS: This trial will inform the future implementation of cancer rehabilitation by providing important data about efficacy, safety, cost, and patient experience. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001417875; https://tinyurl.com/yc5crwtr. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38553.

Prenatal Diagnosis of Vasa Previa by Routine Transvaginal Color Doppler.

The prenatal diagnosis of vasa previa is essential to achieving a safe delivery in patients who suffer from the condition. Transvaginal ultrasound with color Doppler performed at the time of a routine mid-trimester ultrasound is a valuable tool in terms of achieving a timely and accurate diagnosis of vasa previa.

An International Virtual COVID-19 Critical Care Training Forum for Healthcare Workers.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in redeployment of non-critical care-trained providers to intensive care units across the world. Concurrently, traditional venues for delivery of medical education faced major disruptions. The need for a virtual forum to fill knowledge gaps for healthcare workers caring for patients with coronavirus disease (COVID-19) was apparent in the early stages of the pandemic. Objective: The weekly, open-access COVID-19 Critical Care Training Forum (CCCTF) organized by the American Thoracic Society (ATS) provided a global audience access to timely content relevant to their learning needs. The goals of the forum were threefold: to aid healthcare providers in assessment and treatment of patients with COVID-19, to reduce provider anxiety, and to disseminate best practices. Methods: The first 13 ATS CCCTF sessions streamed live from April to July 2020. Structured debriefs followed each session and participant feedback was evaluated in planning of subsequent sessions. A second set of 14 sessions streamed from August to November 2020. Content experts were recruited from academic institutions across the United States. Results: As of July 2020, the ATS CCCTF had 2,494 live participants and 7,687 downloads for a total of 10,181 views. The majority of participants had both completed training (58.6%) and trained in critical care (53.8%). Physicians made up a majority (82.2%) of the audience that spanned the globe (61% were international attendees). Conclusion: We describe the rapid and successful implementation of an open-access medical education forum to address training and knowledge gaps among healthcare personnel caring for patients with COVID-19.

Development of a National Academic Boot Camp to Improve Fellowship Readiness.

Background: Pulmonary and critical care medicine (PCCM) fellowship requires a high degree of medical knowledge and procedural competency. Gaps in fellowship readiness can result in significant trainee anxiety related to starting fellowship training.Objective: To improve fellowship readiness and alleviate anxiety for PCCM-bound trainees by improving confidence in procedural skills and cognitive domains.Methods: Medical educators within the American Thoracic Society developed a national resident boot camp (RBC) to provide an immersive, experiential training program for physicians entering PCCM fellowships. The RBC curriculum is a 2-day course designed to build procedural skills, medical knowledge, and clinical confidence through high-fidelity simulation and active learning methodology. Separate programs for adult and pediatric providers run concurrently to provide unique training objectives targeted to their learners' needs. Trainee assessments include multiple-choice pre- and post-RBC knowledge tests and confidence assessments, which are scored on a four-point Likert scale, for specific PCCM-related procedural and cognitive skills. Learners also evaluate course material and educator effectiveness, which guide modifications of future RBC programs and provide feedback for individual educators, respectively.Results: The American Thoracic Society RBC was implemented in 2014 and has grown annually to include 132 trainees and more than 100 faculty members. Mean knowledge test scores for participants in the 2019 RBC adult program increased from 55% (±14% SD) on the pretest to 72% (±11% SD; P < 0.001) after RBC completion. Similarly, mean pretest scores for pediatric course attendees increased from 54% (±13% SD) to 62% (±19% SD; P = 0.17). Specific content domains that improved by 10% or more between pre- and posttests included airway management, bronchoscopy, pulmonary function testing, and code management for adult course participants, and airway management, pulmonary function testing, and extracorporeal membrane oxygenation for pediatric course participants. Trainee confidence also significantly improved across all procedural and cognitive domains for adult trainees and in 10 of 11 domains for pediatric course attendees. Course content for the 2019 RBC was overwhelmingly rated as "on target" for the level of learner, with <4% of respondents indicating any specific session was "much too basic" or "much too advanced."Conclusion: RBC participation improved PCCM-bound trainee knowledge, procedural familiarity, and confidence. Refinement of the RBC curriculum over the past 7 years has been guided by educator and course evaluations, with the ongoing goal of meeting the evolving educational needs of rising PCCM trainees.

Evaluating the Introduction of an Allied Health Clinical Research Office at a Health Service: Effects on Research Participation, Interest, and Experience of Allied Health Professionals.

Following the introduction of an allied health clinical research office at a large metropolitan health service, we aimed to measure change in self-reported research participation, interest and experience of allied health professionals. METHODS: Allied health professionals were surveyed using the Research Spider tool in 2015 (n=245), and the results were compared to a similar survey completed in 2007 at the same health service (n=132). RESULTS: Overall, allied health professionals rated themselves as having "some research interest" and "little research experience," with no significant difference from 2007 to 2015. Allied health professionals with at least some research interest reported increased experience in critically reviewing literature (p=0.045) and finding relevant literature (p=0.009) and a trend to increased experience of publishing research (p=0.059) in 2015 compared with 2007. The proportion of allied health professionals who classified themselves as participating in research had increased from 41% in 2007 to 51% in 2015 (p=0.028). CONCLUSIONS: The introduction of an allied health clinical research office has been associated with increased participation in research with some improvements in research experience for those with at least some interest in research. Despite these positive changes, most allied health professionals at this health service still report little research experience and only some interest in research.

Task-evoked functional connectivity does not explain functional connectivity differences between rest and task conditions.

During complex tasks, patterns of functional connectivity differ from those in the resting state. However, what accounts for such differences remains unclear. Brain activity during a task reflects an unknown mixture of spontaneous and task-evoked activities. The difference in functional connectivity between a task state and the resting state may reflect not only task-evoked functional connectivity, but also changes in spontaneously emerging networks. Here, we characterized the differences in apparent functional connectivity between the resting state and when human subjects were watching a naturalistic movie. Such differences were marginally explained by the task-evoked functional connectivity involved in processing the movie content. Instead, they were mostly attributable to changes in spontaneous networks driven by ongoing activity during the task. The execution of the task reduced the correlations in ongoing activity among different cortical networks, especially between the visual and non-visual sensory or motor cortices. Our results suggest that task-evoked activity is not independent from spontaneous activity, and that engaging in a task may suppress spontaneous activity and its inter-regional correlation.

Gottesfeld-Hohler Memorial Foundation Zika Virus Think Tank Summary.

At a think tank bringing together experts on fetal neuroimaging, obstetric infectious diseases, and public health, we discussed trends in all of these areas for Zika virus. There is a wide variety of imaging findings in affected fetuses, influenced by timing of infection and probably host factors. The resources for diagnosis and interventions also vary by location with the hardest hit areas often having the fewest resources. We identified potential areas for both research and clinical collaboration as the Zika virus epidemic continues to evolve.

Design and Early Experience With a Real-World Surgical Registry.

OBJECTIVES: We describe the rationale, design, and methods and 6-year experience with a real-world surgical registry for female pelvic reconstructive and incontinence procedures and postoperative outcomes. METHODS: The primary goal of creating this registry was to establish the feasibility of prospective data capture for all urogynecologic procedures. Data captured included baseline demographics, surgical procedures, perioperative complications, and subjective and objective findings up to 36 months after surgery. RESULTS: The Pelvic Reconstruction and Incontinence Surgery ± Mesh Registry was developed over 3 years to include 194 unique variables for prospective data capture. The registry was implemented in December 2010, and data from 924 separate case events from a single surgeon were recorded, comprising 100% surgical case capture. Cases included a variety of procedures representing a comprehensive urogynecology practice on 804 unique patients. Patients who were asked to participate in long-term follow-up (n = 299) returned with attendance of 96% at 6 weeks, 64% at 6 months, 51% at 12 months, 39% at 24 months, and 22% at 36 months. CONCLUSIONS: The Pelvic Reconstruction and Incontinence Surgery ± Mesh Registry effectively captured all urogynecologic procedures for the purpose of quality improvement. This real-world tool demonstrates that 100% case capture is feasible and provides valuable information for the highly motivated surgeon, although adequate long-term follow-up is limited. Additional research is needed to better understand the role of surgical registries for quality improvement and development of patient-centered strategies to increase long-term follow-up.

Prostaglandin E2 receptor 4 mediates renal cell carcinoma intravasation and metastasis.

Treatment options for metastatic renal cell carcinoma (RCC) are limited. In this study, we investigated impact of prostaglandin E2 (PGE2) receptor 4 (EP4) on RCC metastasis. We found that knockdown of EP4 in two RCC cell lines, ACHN and SN12C, does not affect xenograft tumor take or growth rate in mice, but reduces metastasis by decreasing tumor intravasation. Using chick chorioallantoic membrane (CAM) assay, we confirmed that blockade of EP4 signaling inhibits tumor intravasation. In vitro studies associated EP4 expression and activity with RCC cell transendothelial migration (TEM). Gene expression analysis and validation assays showed that EP4 knockdown decreases expression of CD24, a ligand to the adhesion molecule P-selectin. Forced expression of CD24 in EP4 knockdown RCC rescues TEM capacity of the cells. Pharmacologic inhibition or knockdown of endothelial P-selectin blocks EP4-mediated cancer cell TEM, and inhibition of P-selectin prevents RCC tumor intravasation in CAM assay. Our results demonstrate that inhibition of EP4 attenuates the RCC intravasation and metastasis by downregulating CD24 and that P-selectin participates in tumor intravasation, implying a potential for these molecules as therapeutic targets for advanced RCC treatment.

Organisational benefits of a strong research culture in a health service: a systematic review.

Objective The aim of the present study was to determine whether there is an association between having research culture in a health service and better organisational performance. Methods Using systematic review methods, databases were searched, inclusion criteria applied and study quality appraised. Data were extracted from selected studies and the results were synthesised descriptively. Results Eight studies were selected for review. Five studies compared health services with high versus low levels of research activity among the workforce. Three studies evaluated the effect of specific interventions focused on the health workforce. All studies reported a positive association between research activity and organisational performance. Improved organisational performance included lower patient mortality rates (two of two studies), higher levels of patient satisfaction (one of one study), reduced staff turnover (two of two studies), improved staff satisfaction (one of two studies) and improved organisational efficiency (four of five studies). Conclusions A stronger research culture appears to be associated with benefits to patients, staff and the organisation. What is known about this topic? Research investment in the health workforce can increase research productivity of the health workforce. In addition, investment in clinical research can lead to positive health outcomes. However, it is not known whether a positive research culture among the health workforce is associated with improved organisational performance. What does this paper add? The present systematic review of the literature provides evidence that a positive research culture and interventions directed at the health workforce are associated with patient, staff and organisational benefits. What are the implications for practitioners? For health service managers and policy makers, one interpretation of the results could be to provide support for initiatives directed at the health workforce to increase a research culture in health services. However, because association does not imply causation, managers need to interpret the results with caution and evaluate the effect of any initiatives to increase the research culture of the health workforce on the performance of their organisation.

Effectiveness and Duration of Effect of Open-Label Lisdexamfetamine Dimesylate in Adults With ADHD.

OBJECTIVES: (a) Evaluate the efficacy and duration of effect of lisdexamfetamine dimesylate (LDX) in adult ADHD. (b) Assess the reliability and validity of the Adult ADHD Medication Smoothness of Effect Scale (AMSES) and Adult ADHD Medication Rebound Scale (AMRS). METHOD: Adults ( N = 40) with ADHD were treated with LDX for up to 12 weeks. The primary efficacy measure was the ADHD Rating Scale (ADHD-RS). The psychometric properties of the AMSES and AMRS are analyzed and compared with the ADHD-RS, ADHD Self-Report Scale (ASRS) v1.1 Symptom Checklist, and Time-Sensitive ADHD Symptom Scale (TASS). RESULTS: ADHD-RS scores were significantly improved with LDX. The AMSES and AMRS had high internal consistency and were correlated with the ADHD-RS, ASRS v1.1 Symptom Checklist, and TASS. CONCLUSION: LDX is effective in treating adult ADHD and has a smooth drug effect throughout the day with limited symptom rebound. The AMSES and AMRS are valid and reliable measures.

G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer.

G protein-coupled receptor kinases (GRK) regulate diverse cellular functions ranging from metabolism to growth and locomotion. Here, we report an important contributory role for GRK5 in human prostate cancer. Inhibition of GRK5 kinase activity attenuated the migration and invasion of prostate cancer cells and, concordantly, increased cell attachment and focal adhesion formation. Mass spectrometric analysis of the phosphoproteome revealed the cytoskeletal-membrane attachment protein moesin as a putative GRK5 substrate. GRK5 regulated the subcellular distribution of moesin and colocalized with moesin at the cell periphery. We identified amino acid T66 of moesin as a principal GRK5 phosphorylation site and showed that enforcing the expression of a T66-mutated moesin reduced cell spreading. In a xenograft model of human prostate cancer, GRK5 silencing reduced tumor growth, invasion, and metastasis. Taken together, our results established GRK5 as a key contributor to the growth and metastasis of prostate cancer.

Pregnancy after liver transplantation.

UNLABELLED: Several reports on liver transplantation and pregnancy have been published recently. Uncertainty remains regarding appropriate management of these patients. METHODS: The study included pregnant women of all ages with liver transplant referred to our center. A total of eight patients were identified and qualified for our study. The following variables were obtained: age, date of liver transplantation, date of conception, reasons for liver transplantation, type of immunosuppressive therapy, complications during pregnancy, gestational age at birth, birth weight, mode of delivery, the interval of time from liver transplantation to conception and co-morbidity. RESULTS: The mean age of our population was 24 years. Four of the eight were nulliparous. The mean time interval from transplantation to pregnancy was eight years. The indication for liver transplantation in 75% of patients was autoimmune hepatitis. Two cases were associated with viral hepatitis. Combination therapy with more than one immunosuppressant was given to 75% of patients. The most prevalent complication was pyelonephritis in (38%), followed by gestational thrombocytopenia and preeclampsia. Most deliveries (75%) were vaginal and at term (88%). The median for gestational age was 39 weeks. The median birth weight was 2,898 grams. CONCLUSIONS: This study proves that successful and uneventful pregnancies are likely in liver transplant patients under optimal obstetric management.

Effectiveness and safety of lidocaine in the induction of fetal cardiac asystole for second trimester pregnany termination.

UNLABELLED: The presence of a major congenital anomaly is a frequent indication for late termination of pregnancy. The possibility of the fetus being born alive is significant, thus, feticide prior to the procedure is desirable. The purpose of this study was to assess the safety and efficacy of lidocaine 1% as a feticidal agent prior to second trimester termination of pregnancy. METHODS: We conducted a chart review of all patients who underwent a second trimester termination of pregnancy at our institution between March 2009 and June 2012. We collected data regarding the indication for the termination procedure, gestational age, site of lidocaine injection, dosage of lidocaine, need for additional to produce asystole, and maternal complications. RESULTS: We identified 54 patients who underwent second trimester termination following injection with lidocaine. Forty-six cases (85%) were done for major fetal anomalies and 8 cases (15%) were for maternal indications. The mean gestational age was 22 weeks (SD = 2.3). The mean volume of lidocaine 1% injected was 10.1 mL (range: 5-40 mL). Asystole was achieved in 1-2 minutes following intracardiac administration. Intracardiac injection was successful in 45/46 (98%) of cases. Intrathoracic administration was successful in 5/6 (83%). This approach was chosen when cardiac puncture was not effective. Two fetuses receiving an initial intraabdominal or umbilical vein injection required additional doses of intracardiac lidocaine to produce asystole. There were no maternal complications. CONCLUSIONS: Intracardiac administration of lidocaine is an effective method to induce cardiac asystole for second trimester pregnancy termination. Extra-cardiac injection, however, is less effective.

Prenatal diagnosis of a vein of Galen aneurysmal malformation using color Doppler ultrasound: a case report.

Vein of Galen aneurysms are a rare and complex vascular malformation of the brain. Their prevalence is somewhat less than 1 in 25,000 deliveries. Common associated anomalies include ventriculomegaly, cardiomegaly secondary to high cardiac output and enlarged neck vessels, the later being an almost pathognomonic sign. The prognosis for these neonates is poor with a mortality rate of 50% and a high risk for neurologic sequelae. Color flow Doppler studies of the fetal brain vasculature are a reliable method for diagnostic purposes. In this paper we present a case of a vein of Galen malformation diagnosed prenatally at 33 weeks of gestation using both 2D and color Doppler ultrasound modalities.

Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study.

OBJECTIVES: The study objectives were to 1) evaluate medication adherence for adults with attention-deficit/hyperactivity disorder (ADHD) treated with 3 times daily (TID) mixed amphetamine salts immediate release (MAS IR) versus once-daily (qAM) MAS extended release (MAS XR) in a randomized, crossover study; and 2) to examine the associations between adherence and efficacy for MAS IR and MAS XR. METHODS: Sixty-two adults with ADHD were enrolled and 49 completed the study. The treatment condition order (TID-qAM or qAM-TID) was counterbalanced across participants, with an intervening washout period of ≥ 7 days. Adherence was assessed via 3 measures: 1) self-report, 2) pill count, and 3) the Medication Event Monitoring System (MEMS(®)). The primary efficacy measure was the ADHD Rating Scale (ADHD-RS); secondary measures included the Time-Sensitive ADHD Symptom Scale (TASS) and Clinical Global Impressions-Severity of Illness (CGI-S) scale. RESULTS: Adherence to treatment as measured by self-report and pill count was not significantly different between MAS XR and MAS IR. Adherence was significantly better for MAS XR than MAS IR for all of the MEMS(®) measures. The mean change in ADHD-RS, TASS, and CGI-S scores at endpoint was significantly improved for both MAS IR and MAS XR and did not differ significantly between groups. There was not a significant adherence by efficacy interaction. CONCLUSION: Adults with ADHD adhered equally well with MAS IR as with MAS XR when assessed by pill count and self-report, but not by the MEMS(®) measures. Both treatments significantly reduced ADHD symptoms, and efficacy was not significantly different between groups. Adherence was not associated with treatment outcome.

Reduced interhemispheric resting state functional connectivity in cocaine addiction.

BACKGROUND: Models of cocaine addiction emphasize the role of disrupted frontal circuitry supporting cognitive control processes. However, addiction-related alterations in functional interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. We examined interhemispheric resting-state functional connectivity (RSFC) in cocaine dependence using a recently validated approach, voxel-mirrored homotopic connectivity. METHODS: We compared interhemispheric RSFC between 25 adults (aged 35.0 ± 8.8) meeting DSM-IV criteria for cocaine dependence within the past 12 months but currently abstaining (>2 weeks) from cocaine and 24 healthy comparisons (35.1 ± 7.5), group-matched on age, sex, education, and employment status. RESULTS: We observed reduced prefrontal interhemispheric RSFC in cocaine-dependent participants relative to control subjects. Further analyses demonstrated a striking cocaine-dependence-related reduction in interhemispheric RSFC among nodes of the dorsal attention network, comprising bilateral lateral frontal, medial premotor, and posterior parietal areas. Further, within the cocaine-dependent group, RSFC within the dorsal attention network was associated with self-reported attentional lapses. CONCLUSIONS: Our findings provide further evidence of an association between chronic exposure to cocaine and disruptions within large-scale brain circuitry supporting cognitive control. We did not detect group differences in diffusion tensor imaging measures, suggesting that alterations in the brain's functional architecture associated with cocaine exposure can be observed in the absence of detectable abnormalities in the white matter microstructure supporting that architecture.

Antenatal screening for Down syndrome with special considerations in the Puerto Rican population.

Down syndrome is the most studied chromosomal abnormality, and the risk of having a child with Down syndrome increases as maternal age increases. The prevalence of Down syndrome has been increasing in the last decade because more women older than 35 years of age are having children. In recent decades, the rate of identification of fetal anomalies in the uterus has substantially increased. Diagnostically speaking, serious concerns yet remain within the obstetrical community regarding who should be recommended for invasive procedures. The FASTER, SURUSS, and BUN studies have attempted to address this issue. In the United States, the quadruple screen for Down syndrome (hcG, AFP, estriol, and inhibin-A) is the most commonly used test today. During the first trimester, the nuchal translucency measurement combined with serum markers hcG and PAPP-A (pregnancy-associated plasma protein-A) results in high detection rates and low false-positive rates. For Down syndrome screening, new methods of evaluation have been proposed; among these are integrated, sequential, and contingent modalities. Different trials have demonstrated that first-trimester screening for Down syndrome is very effective, but all conclude that combining screening during both trimesters allows for lower false-positive values and higher detection rates. In Puerto Rico, in spite of the fact that a large proportion of the population undergoes serum screening, the rate of Down syndrome live births remains steady. One important aspect that appears to limit prenatal diagnosis of Down syndrome in our population is a poor acceptance rate of diagnostic testing techniques such as amniocentesis. Also, a limited efficiency in the implementation of these screening methods as well as their diagnostic success has been observed for our patient population.