Severe Maternal Morbidity among Women in the U. S. Military, 2003-2015.

OBJECTIVE: This study aimed to assess trends and correlates of severe maternal morbidity at delivery among active duty women in the U.S. military, all of whom are guaranteed health care and full employment. STUDY DESIGN: Linked military personnel and medical encounter data from the Department of Defense Birth and Infant Health Research program were used to identify a cohort of delivery hospitalizations among active duty military women from January 2003 through August 2015. Cases of severe maternal morbidity were identified by applying 21- and 20-condition algorithms (with and without blood transfusion) developed by the Centers for Disease Control and Prevention. Rates (per 10,000 delivery hospitalizations) were reported overall and by specific condition. Multivariable Poisson regression models estimated associations with demographic, clinical, and military characteristics. RESULTS: Overall, 187,063 hospitalizations for live births were included for analyses. The overall 21- and 20-condition severe maternal morbidity rates were 111.7 (n = 2089) and 37.4 (n = 699) per 10,000 delivery hospitalizations, respectively. The 21-condition rate increased by 184% from 2003 to 2015; the 20-condition rate increased by 40%. Compared with non-Hispanic White women, the adjusted 21-condition rate of severe maternal morbidity was higher for Hispanic (adjusted rate ratio [aRR] = 1.28, 95% confidence interval [CI]: 1.13-1.46), non-Hispanic Black (aRR = 1.34, 95% CI: 1.21-1.49), Asian/Pacific Islander (aRR = 1.35, 95% CI: 1.13-1.61), and American Indian/Alaska Native (aRR = 1.39, 95% CI: 1.06-1.82) women. Rates also varied by age, clinical factors, and deployment history. CONCLUSION: Active duty U.S. military women experienced an increase in severe maternal morbidity from 2003 to 2015 that followed national trends, despite protective factors such as stable employment and universal health care. Similar to other populations, military women of color were at higher risk for severe maternal morbidity relative to non-Hispanic White military women. Continued surveillance and further investigation into maternal health outcomes are critical for identifying areas of improvement in the Military Health System. KEY POINTS: · Cesarean delivery and multiple birth were the strongest correlates of severe maternal morbidity in this population.. · Racial disparities persisted across indicators of severe maternal morbidity.. · Rates of disseminated intravascular coagulation were higher than those reported nationally..

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media.

Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen Streptococcus pneumoniae target the bacterial capsular polysaccharide and confer no protection against nonencapsulated strains or capsular types outside vaccine coverage. Mucosal infections such as acute otitis media remain prevalent, even those caused by vaccine-covered serotypes. Here, we report that a protein-based vaccine, a fusion construct of epitopes of CbpA to pneumolysin toxoid, confers effective protection against pneumococcal acute otitis media for non-PCV-13 serotypes and enhances protection for PCV-13 serotypes when coadministered with PCV-13. Having cross-reactive epitopes, the fusion protein also induces potent antibody responses against nontypeable Haemophilus influenzae and S. pneumoniae, engendering protection against acute otitis media caused by emerging unencapsulated otopathogens. These data suggest that augmenting capsule-based vaccination with conserved, cross-reactive protein-based vaccines broadens and enhances protection against acute otitis media.

Efficacy of Aminomethyl Spectinomycins against Complex Upper Respiratory Tract Bacterial Infections.

The most frequent ailment for which antibiotics are prescribed is otitis media (ear infections), which is most commonly caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae Treatment of otitis media is complicated by the fact that the bacteria in the middle ear typically form biofilms, which can be recalcitrant to antibiotic treatment. Furthermore, bacterial respiratory infections can be greatly exacerbated by viral coinfection, which is particularly evidenced by the synergy between influenza and S. pneumoniae In this study, we sought to ascertain the in vivo efficacy of aminomethyl spectinomycin lead 1950, an effective antibacterial agent both in vitro and in vivo against Streptococcus pneumoniae in the context of complex respiratory infections and acute otitis media. A single dose of 1950 significantly reduced bacterial burden in the respiratory tract for all three pathogens, even when species were present in a coinfection model. Additionally, a single dose of 1950 effectively reduced pneumococcal acute otitis media from the middle ear. The agent 1950 also proved efficacious in the context of influenza-pneumococcal super infection. These data further support the development of this family of compounds as potential therapeutic agents against the common causes of complex upper respiratory tract infections and acute otitis media.

Controlled mechanical vibration and impacts on skin biology.

BACKGROUND AND OBJECTIVE: Different biological models have shown how mechanical stimulation may induce physiological responses from solicited cells, tissues, or organs. In models of cultured skin cells, the frequency of the mechanical stress appears to be a paramount parameter, generating a biological response in some cells, particularly from dermal fibroblasts. Our objective was to explore in ex vivo human skin explants the effects of mechanical stimulation. MATERIALS AND METHODS: Mechanical stimulations were provided by a torque test device, with different end effectors, able to generate cyclic strains at different frequencies (from 40 to 120 Hz). Skin explant samples were stimulated twice daily by the device for one minute, over 10 days. RESULTS: At days 0, 5, and 10, samples were processed by immunohistological procedures, allowing some structural dermal proteins to be quantified (fluorescence). As compared to untreated skin explant samples, the stimulation procedure clearly led some proteins of the dermal-epidermal and some dermal proteins to be overexpressed. This stimulation was found to be frequency-dependent, with the greatest overall increases occurring at 60 and 90 Hz. CONCLUSION: For the first time, ultrafast ultrasound imaging in vitro (phantom mimicking skin mechanical properties) was used to analyze mechanical waves transmitted to the skin layers as a function of end effector shape.

Long-Term Effect of Lactation on Maternal Cardiovascular Function and Adiposity in a Murine Model.

OBJECTIVE: Epidemiological studies suggest that lactation is associated with long-term maternal health benefits. To avoid confounders in human studies, we used a previously characterized murine model to investigate the long-term effect of lactation on both cardiovascular function and adiposity. STUDY DESIGN: After the delivery of the pups, CD-1 female mice were randomly divided into two groups: lactated and nonlactated (NL). Before pregnancy and at 9 months postdelivery, blood pressure was measured using a tail cuff, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT), echocardiography was performed using microultrasound, and cholesterol panels and fasting blood glucose were measured. The data were analyzed using Student's t-test (significance at p < 0.05). RESULTS: There were no differences in baseline parameters between the two groups. At 9 months postdelivery, the NL group weighed significantly more (p = 0.03) and demonstrated a significantly lower cardiac output (p = 0.05) and ejection fraction (p = 0.03). The mice in the NL group also had higher VAT (p < 0.01) and SAT percentiles (p = 0.03). Fasting glucose (p = 0.01) and low-density lipoprotein (p = 0.01) were significantly higher in the NL group at 9 months. CONCLUSION: Our results show the benefit of lactation is not just limited to the immediate postpartum period but it also extends into midlife in a murine model.

Towards an understanding of regulating Cajal body activity by protein modification.

The biogenesis of small nuclear ribonucleoproteins (snRNPs), small Cajal body-specific RNPs (scaRNPs), small nucleolar RNPs (snoRNPs) and the telomerase RNP involves Cajal bodies (CBs). Although many components enriched in the CB contain post-translational modifications (PTMs), little is known about how these modifications impact individual protein function within the CB and, in concert with other modified factors, collectively regulate CB activity. Since all components of the CB also reside in other cellular locations, it is also important that we understand how PTMs affect the subcellular localization of CB components. In this review, we explore the current knowledge of PTMs on the activity of proteins known to enrich in CBs in an effort to highlight current progress as well as illuminate paths for future investigation.

Hemostatic Resuscitation in Peripartum Hysterectomy Pre- and Postmassive Transfusion Protocol Initiation.

Background Massive transfusion protocols (MTPs) have been examined in trauma. The exact ratio of packed red blood cells (PRBC) to other blood replacement components in hemostatic resuscitation in obstetrics has not been well defined. Objective The objective of this study was to evaluate hemostatic resuscitation in peripartum hysterectomy comparing pre- and postinstitution of a MTP. Study Design We conducted a retrospective, descriptive study of women undergoing peripartum hysterectomies from January 2002 to January 2015 who received ≥ 4 units of PRBC. Individuals were grouped into either a pre-MTP institution group or a post-MTP institution group. The post-MTP group was subdivided into those who had the protocol activated (MTP) versus not activated (no MTP). Primary outcomes were estimated blood loss (EBL) and need for blood product replacement. The secondary outcome was a composite of maternal morbidity, including need for mechanical ventilation, venous thromboembolism, pulmonary edema, acute kidney injury, and postpartum infection. A Mann-Whitney U test was used to compare continuous variables, and a chi-squared test was used for categorical variables with significance of p < 0.05. Results Of the 165 women who had a peripartum hysterectomy during the study period, 62 received four units or more of PRBC. No significant differences were noted in EBL or blood product replacement between the pre-MTP (n = 39) and post-MTP (n = 23) groups. Similarly, the MTP (n = 6) and no MTP (n = 17) subgroups showed no significant difference between EBL and overall blood product replacement. Significant differences were seen in transfusion of individual blood products, such as fresh frozen plasma (FFP) (MTP = 4, no MTP = 2; p = 0.02) and platelets (plts) (MTP = 6, no MTP = 0; p = 0.03). The use of high ratio replacement therapy for both plasma and plts was more common in the MTP group (FFP/PRBC ratio [MTP = 0.5, no MTP = 0.3; p = 0.02]; plts/PRBC ratio [MTP = 0.7, no MTP = 0; p = 0.03]). There were no differences in the secondary outcome between pre- and post-MTP or MTP and no MTP. Conclusion Initiation of the MTP did result in an increase in transfusion of FFP and plts intraoperatively. At our institution, the MTP is underutilized, but it appears that providers are more cognizant of the use of high transfusion ratios.

Identification of processing elements and interactors implicate SMN, coilin and the pseudogene-encoded coilp1 in telomerase and box C/D scaRNP biogenesis.

Many cellular functions, such as translation, require ribonucleoproteins (RNPs). The biogenesis of RNPs is a multi-step process that, depending on the RNP, can take place in many cellular compartments. Here we examine 2 different RNPs: telomerase and small Cajal body-specific RNPs (scaRNPs). Both of these RNPs are enriched in the Cajal body (CB), which is a subnuclear domain that also has high concentrations of another RNP, small nuclear RNPs (snRNPs). SnRNPs are essential components of the spliceosome, and scaRNPs modify the snRNA component of the snRNP. The CB contains many proteins, including WRAP53, SMN and coilin, the CB marker protein. We show here that coilin, SMN and coilp1, a newly identified protein encoded by a pseudogene in human, associate with telomerase RNA and a subset of scaRNAs. We also have identified a processing element within box C/D scaRNA. Our findings thus further strengthen the connection between the CB proteins coilin and SMN in the biogenesis of telomeras e and box C/D scaRNPs, and reveal a new player, coilp1, that likely participates in this process.

Effect of lactation on maternal postpartum cardiac function and adiposity: a murine model.

OBJECTIVE: Lactation is associated with reduction in maternal metabolic disease and hypertension later in life; however, findings in humans may be confounded by socioeconomic factors. We sought to determine the independent contribution of lactation on cardiovascular parameters and adiposity in a murine model. STUDY DESIGN: Following delivery, CD-1 female mice were randomly divided into 2 groups: lactated (L; nursed pups for 3 weeks, n = 10), and nonlactated (NL; pups were removed after birth, n = 12). Blood pressure (BP) was assessed prepregnancy and at 1 and 2 months' postpartum. Visceral and subcutaneous adipose tissue determined by computed tomography and left ventricular ejection fraction, cardiac output, and the E/A ratio determined by microultrasound were evaluated at 1 and 2 months' postpartum. The results were analyzed using a Student t test (significance at P < .05). RESULTS: We observed a significantly different maternal BP at 2 months' postpartum with relatively greater BP in NL (systolic BP: NL, 122.2 ± 7.2 vs L, 96.8 ± 9.8 mm Hg; P = .04; diastolic BP: NL, 87.0 ± 6.8 vs L, 65.9 ± 6.2 mm Hg; P = .04). Visceral adipose tissue was significantly increased in NL mice at 1 (22.0 ± 4.1% vs 10.7 ± 1.8%, P = .04) and 2 months' postpartum (22.9 ± 3.5% vs 11.2 ± 2.2%, P = .02), whereas subcutaneous adipose tissue did not differ between the groups. At 2 months' postpartum, ejection fraction (51.8 ± 1.5% vs 60.5 ± 3.8%; P = .04), cardiac output (14.2 ± 1.0 vs 18.0 ± 1.3 mL/min; P = .02) and mitral valve E/A ratio (1.38 ± 0.06 vs 1.82 ± 0.13; P = .04) were significantly lower in NL mice than L mice. CONCLUSION: Our data provide evidence that interruption of lactation adversely affects postpartum maternal cardiovascular function and adiposity.

Early abdominal ectopic pregnancies: a systematic review of the literature.

OBJECTIVE: To define abdominal ectopic pregnancy outcomes by both location and treatment. METHODS: Literature review of abdominal pregnancies from 1965 to August of 2009. Ectopic pregnancy exclusions were interstitial, tubal, cervical, ovarian, or those beyond 20 weeks at diagnosis/treatment. RESULTS: There were 511 cases identified with 225 meeting the inclusion criteria. There were 7 maternal deaths (3.0%) with 18 (8%) of the early abdominal ectopic pregnancies occurring with an intrauterine device in place. Mean gestational age at the time of treatment was 10 weeks 0 days and mean maternal age was 29.7 years. The average blood loss associated with treatment was 1,450 ml. The top three sites of early abdominal ectopic pregnancies were pouches around the uterus (24.3%), serosal surface of the uterus and tubes (23.9%), and multiple sites (12.8%). Primary surgical management was performed in 208 cases (87.8%). Nonsurgical adjuvant or primary therapy included intramuscular methotrexate, intralesional methotrexate, intracardiac KCl, and artery embolization. CONCLUSION: Abdominal pregnancies should be considered in all patients until an intrauterine location can be confirmed. Understanding treatment options by pregnancy location may be helpful in the management of this potentially life-threatening condition.

Quantification of Blood Loss Improves Detection of Postpartum Hemorrhage and Accuracy of Postpartum Hemorrhage Rates: A Retrospective Cohort Study.

Objective To evaluate the ability of estimated blood loss (EBL) and quantitative blood loss (QBL) to predict the need for blood transfusion in postpartum patients. Methods This is a retrospective observational study involving all deliveries one year before and after the change from EBL to QBL assessment in June 2017. Blood loss, need for blood transfusion, admission hematocrit, and postpartum nadir hematocrit were collected. Descriptive and bivariable analyses were performed. Receiver operator curves were compared. Results Overall, the baseline characteristics between the EBL (n=2743) and QBL (n=2,712) groups were similar. Although there was a higher rate of blood loss ≥ 1,000 mL in QBL vs EBL (6.5% vs 2.1%, P<0.001), there was no difference in the rate of blood transfusions (2.0% vs 2.0%, P=1). Among cesarean deliveries, QBL outperformed EBL for predicting blood transfusion and/or ≥10 point drop in hematocrit (AUC 0.75 vs 0.66, P=0.02). QBL also outperformed EBL for predicting transfusion after vaginal delivery (AUC 0.93 vs 0.81, P=0.03).  Conclusion QBL is a more sensitive test for detecting clinically significant blood loss, which could lead to earlier recognition of hemorrhage and interventions.

Abnormal 1 hour glucose challenge test followed by a normal 3 hour glucose tolerance test: does it identify adverse pregnancy outcome?

OBJECTIVE: To determine if pregnancies with an abnormal glucose challenge test (GCT) but a normal (GTT) are at increased risk for fetal macrosomia or an adverse pregnancy outcome. STUDY DESIGN: This prospective observational study matched women with an abnormal glucose challenge test and a normal GTT with the next patient with a normal GCT. RESULTS: Over 12 months, 107 women with abnormal GCT were matched with 107 women with normal GCT. Women with an abnormal GCT were older (27.3 vs. 24.7, p = 0.001) and less likely to be African-American (OR = 2.2, 95% CI 1.06-4.49) but no more likely to have an adverse pregnancy outcome. ROC curves could not differentiate between macrosomic vs non-macrosomic newborns using GCT values. CONCLUSION: Women with an abnormal GCT but a normal GTT are more likely to be older, less likely to be African-American, but no more likely to have an adverse pregnancy outcome or a macrosomic fetus.

Attendance and Quality and Quantity of Research Presentations at an Obstetrics and Gynecology Regional Meeting Pre- and Postchanges in Federal Funding.

INTRODUCTION: Participating in scientific meetings offers value to physician trainees and faculty. In 2012, the U.S. Government (including the Department of Defense) instituted restrictions on conference travel, requiring central approval to attend. Hence, our objective was to determine the academic impact of research presented at the American College of Obstetricians and Gynecologists (ACOG) Armed Forces District Meeting and the effect of this federally mandated policy change on attendance and the quality and quantity of research. MATERIALS AND METHODS: Attendance logs and meeting programs were reviewed for the 3 years immediately before and after institution of travel regulations. A PubMed search of each abstract was performed to determine if it resulted in publication and the mean duration in months from presentation to publication was calculated and compared between oral and poster presentations. The top journals accepting manuscripts were noted along with the corresponding impact factor. RESULTS: The overall meeting publication rate was 22%. Oral presentations were significantly more likely than posters to achieve publication (P < 0.001). Following implementation of travel regulations, mean faculty attendance declined from 130 per year to 105 (P < 0.05). Declines in resident attendance and publication rates were not statistically significant. The top journals publishing investigations included Obstetrics and Gynecology (n = 15), Military Medicine (n = 12), and Fertility and Sterility and Gynecologic Oncology (tied, both n = 11). CONCLUSION: Approximately one in five presentations at the ACOG Armed Forces District Meeting are published, many in high impact journals within the specialty. Implementation of stricter travel regulations adversely impacted faculty physician attendance, but not trainee participation or the publication rate.

Multimodal Stepwise Approach to Reducing In-Hospital Opioid Use After Cesarean Delivery: A Quality Improvement Initiative.

OBJECTIVE: To evaluate the association of a standardized, structured approach to in-hospital postcesarean delivery pain management with maternal opioid use after cesarean delivery. METHODS: We conducted a retrospective cohort study of women who underwent cesarean delivery before and after a quality improvement intervention at a single tertiary care center. A multidisciplinary task force revised electronic order sets for all patients who underwent cesarean delivery with neuraxial anesthesia. The revised order set separated acetaminophen from opioids, scheduled acetaminophen and nonsteroidal antiinflammatory drug administration, and limited opioid use to breakthrough pain. Data were collected by electronic chart review. The primary outcome was median morphine milligram equivalents per hospital stay. Secondary outcomes included median morphine milligram equivalents per day, median pain scores, time to discharge, and opioid-nonopioid pain medication use. Descriptive and bivariable analyses were performed. RESULTS: There were no significant differences in baseline characteristics in the preintervention (n=283) and postintervention (n=286) groups. There was a 75% reduction in median morphine milligram equivalents per stay from 120 (90-176 interquartile range) preintervention to 30 (5-68) postintervention (P<.001) and a 77% reduction in median morphine milligram equivalents per day (51 [41-60] vs 12 [2-25], P<.001). There was no difference between groups in time to discharge or median pain scores. There was no difference in ketorolac use (80% preintervention vs 75% postintervention, P=.14) or in median ibuprofen mg per day (1,391 preintervention vs 1,347 postintervention, P=.22). There was an increase in median acetaminophen mg per day (753 preintervention vs 2,340 postintervention, P<.001). There was a significant increase in patients who used no opioids during their hospital stay (6% preintervention vs 19% postintervention, P<.001). CONCLUSION: A multimodal stepwise approach to postcesarean delivery pain control was associated with markedly reduced opioid consumption without increasing hospital stay or median pain scores. By separating acetaminophen from opioids and limiting opioids to breakthrough pain, we were able to operationalize a tier-based approach to pain management.

Obstetric Hemorrhage Outcomes by Intrapartum Risk Stratification at a Single Tertiary Care Center.

Introduction Postpartum hemorrhage is a leading cause of maternal mortality worldwide. Performance of a postpartum hemorrhage risk assessment prior to delivery has been recommended to identify patients at higher risk for hemorrhage to support advanced planning for optimal response. The objective of this quality improvement initiative is to evaluate the transfusion and hemorrhage rates for patients at low, moderate, and high risk for postpartum hemorrhage by utilizing standardized risk assessment. Methods and materials A historic cohort study was performed among women delivering from March 2017 to June 2018 at a single United States military tertiary medical center. A postpartum hemorrhage risk assessment was performed utilizing the California Maternal Quality Care Collaborative toolkit for all patients admitted to Labor and Delivery and when the postpartum hemorrhage risk increased during the intrapartum period. An electronic log was reviewed to determine blood loss volume, change in hematocrit, and transfusion rates in patients at low, moderate, and high risk for postpartum hemorrhage for all deliveries, stratified by delivery type. Results There were 3,377 deliveries during the study period with 145 excluded due to lack of assigned risk category. The high-risk group (12.3% of deliveries) was 4.3 times more likely to receive a blood transfusion, 2.9 times more likely to have a blood loss over 1000 mL, and 2.1 times more likely to have a transfusion or hematocrit drop of 10 points when compared with the low-risk group (69.4% of deliveries). Of those transfused, the majority were classified as low risk as this was the most common assignment. Conclusion Risk stratification can differentiate low from high-risk patients for postpartum hemorrhage and associated transfusion or change in hematocrit. However, the majority of patients who receive a transfusion will be classified as low or moderate risk. Thus, all patients should be monitored closely and treated aggressively to prevent morbidity.

Pyelonephritis in Pregnancy: Relationship of Fever and Maternal Morbidity.

Objective To evaluate the relationship between maternal fever at the time of hospital admission and subsequent maternal morbidity in pregnant patients with pyelonephritis. Study Design In this retrospective cohort study, inpatient records were reviewed for all obstetric patients discharged from a single tertiary care hospital between June 1, 2011, and May 30, 2017, with the diagnosis of pyelonephritis. Patients were stratified into two groups, those with and without fever at the time of admission. Descriptive statistics were utilized to evaluate the association of fever at the time of presentation with subsequent morbidity. Using admission vital signs, maternal early warning criteria (MEWC) were applied and odds ratios calculated to predict intensive care unit (ICU) admission. Results A total of 110 patients were admitted with pyelonephritis in pregnancy; 24 patients were febrile and 86 patients were afebrile on admission. There was no difference in rates of maternal ICU admission between both groups. Positive MEWC was predictive of ICU admission with an adjusted odds ratio of 16.54 (95% confidence interval: 1.29-212.5; p = 0.03). Conclusion Afebrile pregnant patients with pyelonephritis remain at risk of significant maternal morbidity. Application of the MEWC on admission identifies patients at higher risk of ICU admission.

Introduction of Posterior Axilla Sling Traction in Simulated Shoulder Dystocia.

Objective Aim of this study was to introduce posterior axilla sling traction (PAST) in delivering providers and nursing staff as an adjunct to the management of shoulder dystocia and evaluate comfort in performing the maneuver. Methods A presimulation questionnaire had given to all participants. A brief training on how to perform PAST was also given. A simulated shoulder dystocia was run where usual maneuvers failed. Participants used PAST for delivery of posterior shoulder, delivery of posterior arm, and to assist with rotation. Participants were then given a post-simulation questionnaire. A Chi-squared test was used to evaluate comfort with performing the procedure pre and post-simulation. Results Data were collected from 43 participants at pre and post-simulation. Designations (attending, resident, midwife, registered nurse) and responses were recorded to the questionnaires. There was a statistically significant increase in the number of providers and nurses who would feel comfortable using PAST for shoulder dystocia management and for rotational maneuvers. Ninety-three percent of participants would consider using PAST in future shoulder dystocia when usual maneuvers failed. Conclusion PAST is an adjunct to management of shoulder dystocia that has not previously been taught in our facility. The majority of participants in our simulation felt comfortable with using PAST.

A Novel Mutation in ACTG2 Gene in Mother with Chronic Intestinal Pseudoobstruction and Fetus with Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

Background. A novel mutation in the ACTG2 gene is described in a pregnant patient followed up for chronic intestinal pseudoobstruction (CIPO) during pregnancy and her fetus with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS). Case. 24-year-old gravida 1 para 1 with CIPO and persistent nausea and vomiting in pregnancy, admitted at 28 weeks of gestation. Ultrasound revealed a fetus measuring greater than the 95th percentile, polyhydramnios, and megacystis. At delivery, the newborn was noted to have an enlarged bladder, microcolon, and intolerance of oral intake. Genetic testing of mother and child revealed a novel mutation in the ACTG2 gene (C632F>A, p.R211Q). Conclusion. This is the first case in the literature describing a novel mutation in ACTG2 associated with visceral myopathy affecting both mother and fetus/neonate. Visceral myopathy should be included in the differential diagnosis of megacystis diagnosed by ultrasound, and suspicion should increase with family history of CIPO or MMIHS.

Regulatory RNPs: a novel class of ribonucleoproteins that potentially contribute to ribosome heterogeneity.

Many ribonucleoproteins (RNPs), which are comprised of noncoding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP), which contributes to the biogenesis of small nuclear RNPs (snRNPs) that are central components of the spliceosome. Three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here, we provide data that show that these RNAs become part of RNPs we term regulatory RNPs (regRNPs). Most modifications within rRNA (predominantly pseudouridylation and ribose 2'-O-methylation) are conducted by small nucleolar RNPs (snoRNPs), and we provide evidence that the activity of at least some of these snoRNPs is under the control of regRNPs. Because modifications within rRNA can vary in different physiological or pathological situations, rRNA modifications are thought to be the major source of ribosome heterogeneity. Our identification of regRNPs thus provides a potential mechanism for how ribosome heterogeneity may be accomplished. This work also provides additional functional connections between the Cajal body and the nucleolus.

Adipose Tissue Insulin Resistance in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. METHODS: AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. RESULTS: We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC]glucose). CONCLUSIONS: Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.