Prenatal diagnostic and intervention considerations in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect with significant morbidity and mortality. The prenatal management of a pregnancy with a fetus affected with CDH is complex and requires a multi-disciplinary team approach. An improved understanding of prenatal diagnosis and management is essential to developing strategies to optimize outcomes for these patients. In this review, we explore the current knowledge on diagnosis, severity stratification, prognostic prediction, and indications for fetal intervention in the fetus with CDH.

Maternal obesity: sex-specific in utero changes in fetal brain autophagy and mTOR.

OBJECTIVE: Maternal obesity affects 39.7% of reproductive-age women in the United States. Emerging research has suggested that in utero exposure to maternal obesity is associated with adverse neurodevelopmental outcomes, but knowledge of underlying mechanisms in human samples is lacking. METHODS: A matched case-control study was performed in women with singleton fetuses who were undergoing elective pregnancy termination at gestational ages 15 to 21 weeks. Maternal adiponectin levels from plasma were measured using ELISA kits. RNA was extracted from fetal brain tissue using RNeasy Mini Kit (QIAGEN). mRNA expression from ADIPOR1, ADIPOR2, MTOR, ATG5, ATG7, BECN1, and MAP1LC3B was quantified through the ΔΔCt method and using GAPDH as a housekeeping gene. RESULTS: We have identified transcription patterns associated with inhibition of autophagy in male fetal brain tissue exposed to maternal obesity (↑MTOR, ↓ATG5, ↓ATG7, and ↓MAP1LC3B), with female fetuses demonstrating either no change in transcription or nonsignificant changes associated with increased autophagy. There was significant downregulation of the autophagy-associated gene BECN1 in both male and female individuals who were exposed to obesity in utero. CONCLUSIONS: We present novel evidence suggesting that in utero exposure to maternal obesity in humans may significantly affect neurodevelopment, especially in male fetuses, through alterations in normal autophagy molecular mechanisms and with adiponectin as a potential mediator.

Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin.

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

Effect of a Multimedia Educational Tool on Contraception Use 1 Year Postpartum.

FUNDING SOURCE: Supported in part by a research grant from Investigator-Initiated Studies program of Organon. The opinions expressed in this paper are those of the authors and do not necessarily represent Organon. CLINICAL TRIAL REGISTRAION: ClinicalTrials.gov , NCT04291040.

Maternal and Neonatal Morbidity after Cesarean Delivery for Active Phase Arrest following Adoption of the Obstetric Care Consensus Guidelines.

OBJECTIVE: In an effort to reduce the primary cesarean delivery (CD) rate, the American College of Obstetricians and Gynecologists (ACOG) recommended new labor guidelines in 2014 that allow longer duration of labor times. There are little data on the impact of these guidelines on CD rates and pregnancy outcomes in a predominantly Hispanic population. This study aimed to compare the primary CD rates and maternal and neonatal outcomes in patients undergoing primary CD for arrest of labor before and after implementation of the 2014 guidelines. STUDY DESIGN: This was a retrospective cohort study of term patients who underwent a CD for an arrest disorder between January 2011 and April 2017 at a county teaching hospital. Our primary outcome was the composite maternal and neonatal morbidities (CMM and CNM, respectively). Differences in the demographic and clinical characteristics, CMM, and CNM stratified by time period (pre- vs. postimplementation) were examined. RESULTS: There were 4,976 deliveries in the study period: 525 (11%) underwent primary CD for arrest disorder; 298 (6%) prior to 2014, and 227 (5%) after 2014 (p = 0.62). There was no significant difference in the rate of CD between the two periods (13.4 vs. 13.3%, p = 0.81). In patients undergoing CD for arrest of dilation (n = 389), the CMM and CNM did not significantly change between both groups (63.3 vs. 56%, p = 0.15). In patients who had a CD for arrest of descent (n = 136), the rate of CMM significantly increased from 50 to 75% (p = 0.02) with no significant change in the CNM (13.2 vs. 20%, p = 0.3). CONCLUSION: Despite significant changes in labor management after the publication of the 2014 guidelines, our primary CD rate was not reduced, and we noticed an increase in CMM in patients who had CD for arrest of descent. A randomized controlled trial is needed to further evaluate the effect of these guidelines nationally. KEY POINTS: · The Obstetric Care Consensus statement aims to decrease the rate of cesarean delivery (CD).. · We observed an increase in morbidity in CD if done for arrest of descent (pre/post the consensus).. · A randomized controlled trial is needed to further assess the impact of the guidelines on morbidity..

Experiencias del personal de enfermería ante la muerte perinatal / Experiences of the Nursing Personnel in the Face of Perinatal Death

Introducción: Los profesionales de la salud se encuentran preparados principalmente para recibir vida, por lo cual, brindar cuidados a las mujeres con pérdidas durante la gestación o al inicio de la vida se torna una tarea difícil, cargada de sentimientos y emociones. La muerte perinatal es una situación compleja que tiene un fuerte impacto en las mujeres-madres y en sus familias. Objetivo: Analizar la literatura existente referente a estudios sobre las experiencias del personal de enfermería ante una muerte perinatal. Métodos: Revisión sistemática de la literatura, se realizó una búsqueda en las bases de datos PubMed, EBSCO, CINAHL, Scopus, SciELO y Dianet de febrero a abril del 2020. Los términos de búsqueda utilizados fueron "mortinato", "muerte perinatal", "enfermería" y "experiencias". Se incluyeron artículos en idioma inglés y español, publicados de 2005 a 2020. Como estrategia de búsqueda se utilizó el diagrama de flujo Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), como resultado inicial se obtuvieron 476 artículos, de los cuales, 14 fueron seleccionados por cumplir los criterios de selección. Conclusiones: Las experiencias de los profesionales de enfermería que documentan los estudios recopilados y analizados enfatizan la necesidad de mejorar la formación profesional para acompañar el duelo, así como las estrategias de comunicación y acompañamiento. Las investigaciones reportan experiencias contradictorias, que van desde considerar las pérdidas perinatales como situaciones difíciles de tratar, hasta percepciones positivas que describen como un privilegio u honor el acompañamiento en esos momentos difíciles para las mujeres-madres y sus seres queridos(AU)

Introduction: Health professionals are primarily trained to receive life; therefore, providing care for women with offspring or newborn loss becomes a difficult task, fraught with feelings and emotions. Perinatal death is a complex situation with a strong impact on women-mothers and their families. Objective: To analyze the existing literature regarding studies on the experiences of the nursing personnel in the face of perinatal death. Methods: To carry out the systematic review of the literature, a search was made in the PubMed, EBSCO, CINAHL, Scopus, SciELO and Dianet databases, from February to April 2020. The search terms used were mortinato [stillbirth], muerte perinatal [perinatal death], enfermería [nursing] and experiencias [experiences]. Articles in English and Spanish, published from 2005 to 2020, were included. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flowchart was used as search strategy. As an initial result, 476 articles were obtained, fourteen of which were selected because they met the selection criteria. Conclusions: The experiences of nursing professionals documented in the collected and analyzed studies emphasize the necessity to improve professional training to accompany bereavement, as well as communication and accompaniment strategies. The analyzed researches report contradictory experiences, ranging from considering perinatal losses as difficult situations to deal with, to positive perceptions that describe, as a privilege or honor, accompaniment in these difficult moments for women-mothers and their loved ones(AU)

Nocardiosis linfocutánea en paciente inmunocomprometido

RESUMEN Se presenta el caso de un paciente, agricultor, adulto mayor, portador de hipertensión arterial, cardiopatía isquémica y cáncer de próstata con metástasis en hueso en tratamiento conservador. Acude por cuadro de 15 días de evolución con flictenas en miembro superior y fiebre. Durante su internación se aísla en la secreción de piel Nocardia brasiliensis y es tratado con trimetoprin - sulfametoxazol. En el 15° de internación se agrega una neumonía asociada a los cuidados de la salud. Posteriormente se detecta una lesión ósea destructiva en columna a nivel de L3. Sale de alta con el diagnóstico de nocardiosis linfocutánea en paciente inmunocomprometido a los 31 días de internación con buena respuesta clínica y con planes de continuar antibióticoterapia.

ABSTRACT The case of a patient, an elderly farmer who has hypertension, ischemic heart disease and prostate cancer with bone metastases in conservative treatment, is presented. He consults for a 15-day evolution case with flictenas in the upper limb and fever. During hospitalization, Nocardia basiliensis is isolated in the secretion of skin and is treated with trimethoprine - sulfamethoxazole. In the 15th day of hospitalization, health care-associated pneumonia is added. Subsequently, a destructive bone lesion in the spine is detected at the L3 level. He is discharged with the diagnosis of lymphocutaneous nocardiosis in an immunocompromised patient after 31 days of hospitalization with a good clinical response and with plans to continue antibiotic therapy.

Interprofessional Perceptions and Attitudes Among Pharmacy and Family Nurse Practitioner Students.

INTRODUCTION: Interprofessional education (IPE) activities involving pharmacy (PharmD) and family nurse practitioner (FNP) students is understudied. Interactions between PharmD and FNP students have become important since most recent Accreditation Council for Pharmacy Education standards included a requirement for schools of pharmacy to have IPE. The primary objective of this study is to evaluate the perceptions and attitudes among PharmD and FNP students towards an IPE activity. METHODS: Atleast 1 student from each discipline was assigned to one team and participated in simulated ambulatory care scenarios. A survey was completed by students after the activity, which mapped each survey statement to an Interprofessional Education Collaborative (IPEC) core competency. RESULTS: Perceptions and attitudes between PharmD and FNP students were similar, with no significant differences except with 2 statements, one survey statement in the Teams and Teamwork core competency and another in the Roles/Responsibilities core competency. A less favorable response with more than half of FNP students reporting "strongly agree" (18%) and "agree" (35%) resulted for the statement regarding their professional roles in the IPE activity. CONCLUSION: PharmD and FNP students reported favorable perceptions and attitudes in each IPEC core competency after participation in the IPE activity. There may be a need to review the discipline's professional role before participating in the activity.

Randomised prospective trial to assess the clinical utility of multianalyte assay panel with complement activation products for the diagnosis of SLE.

OBJECTIVE: We compared the physician-assessed diagnostic likelihood of SLE resulting from standard diagnosis laboratory testing (SDLT) to that resulting from multianalyte assay panel (MAP) with cell-bound complement activation products (MAP/CB-CAPs), which reports a two-tiered index test result having 80% sensitivity and 86% specificity for SLE. METHODS: Patients (n=145) with a history of positive antinuclear antibody status were evaluated clinically by rheumatologists and randomised to SDLT arm (tests ordered at the discretion of the rheumatologists) or to MAP/CB-CAPs testing arm. The primary endpoint was based on the change in the physician likelihood of SLE on a five-point Likert scale collected before and after testing. Changes in pharmacological treatment based on laboratory results were assessed in both arms. Statistical analysis consisted of Wilcoxon and Fisher's exact tests. RESULTS: At enrolment, patients randomised to SDLT (n=73, age=48±2 years, 94% females) and MAP/CB-CAPs testing arms (n=72, 50±2 years, 93% females) presented with similar pretest likelihood of SLE (1.42±0.06 vs 1.46±0.06 points, respectively; p=0.68). Post-test likelihood of SLE resulting from randomisation in the MAP/CB-CAPs testing arm was significantly lower than that resulting from randomisation to SDLT arm on review of test results (-0.44±0.10 points vs -0.19±0.07 points) and at the 12-week follow-up visit (-0.61±0.10 points vs -0.31±0.10 points) (p<0.05). Among patients randomised to the MAP/CB-CAPs testing arm, two-tiered positive test results associated significantly with initiation of prednisone (p=0.034). CONCLUSION: Our data suggest that MAP/CB-CAPs testing has clinical utility in facilitating SLE diagnosis and treatment decisions.

Transition of Methotrexate Polyglutamate Drug Monitoring Assay from Venipuncture to Capillary Blood-Based Collection Method in Rheumatic Diseases.

OBJECTIVE: Methotrexate (MTX) polyglutamate (MTXPG3) levels from isolated red blood cells (RBCs) collected by venipuncture have clinical utility in guiding MTX dosing for patients with rheumatoid arthritis (RA). Our objective was to transition this RBC-based therapeutic drug monitoring (TDM) assay to dried capillary blood collected by fingerstick. METHODS: Patients with RA treated with MTX were enrolled. Specimens were collected by fingerstick (volumetric absorptive microsampler) and venipuncture to measure MTXPG3 from dried capillary blood, total venous blood, and isolated RBCs. MTXPG3 levels from dried capillary blood were measured using LC-MS/MS, converted to RBC equivalent (nmol/L), and compared with those from isolated RBCs (reference method). Following transition to fingerstick collection, comparability in the distributions of dried capillary and venipuncture-based RBC MTXPG3 levels was assessed using the Kolmogorov-Smirnov (K-S) test. RESULTS: Intraday and interday precision ranged from 2.0% to 10.9% and 3.1% to 10.8%, respectively, at MTXPG3 concentrations ranging from 5 to 100 nmol/L. In 106 participants treated with MTX, MTXPG3 levels from total venous and dried capillary blood were comparable [slope = 0.97 (95% CI, 0.92-1.03); R 2 = 0.92]. Dried capillary blood MTXPG3 converted to RBC equivalent was similar to levels from isolated RBCs (30 ± 18 nmol/L vs 33 ± 19 nmol/L; n = 106). After implementation in the clinical laboratory, RBC equivalents MTXPG3 from the fingerstick method were similar to levels from venipuncture [39 ± 22 nmol/L (n = 825) vs 39 ± 24 nmol/L (n = 47935)] (K-S test P = 0.09). Underexposure to MTX (MTXPG3 ≤5 nmol/L RBCs) was detected in 7.0% and 8.5% patient specimens collected using the fingerstick and venipuncture methods, respectively. CONCLUSION: Capillary blood MTXPG3 levels can be used to guide MTX dosing in TDM practice.

Ketamina nebulizada para la prevención del dolor faríngeo postoperatorio / Nebulised ketamine for preventing postoperative pharyngeal pain

Resumen: Introducción: El dolor faríngeo postoperatorio es una complicación frecuente posterior a la intubación endotraqueal, caracterizado por odinofagia. Objetivo: Comparar ketamina nebulizada preoperatoria contra placebo para la disminución del dolor faríngeo postoperatorio en cirugía electiva bajo anestesia general. Material y métodos: Estudio experimental prospectivo, aleatorizado, doble ciego, realizado de febrero a julio del 2016. Dos grupos de pacientes aleatorizados: grupo K: ketamina nebulizada (50 mg: 1 mL de ketamina + 2 mL de solución salina 0.9%); grupo P: placebo (nebulización de 3 mL solución salina 0.9%). Se evaluaron signos vitales así como síntomas e intensidad del dolor faríngeo postoperatorio de acuerdo con la escala numérica análoga a la hora 1 y a la hora 4. Resultados: El uso de ketamina nebulizada no representa una ventaja estadísticamente significativa con relación al placebo para el dolor faríngeo postoperatorio. La incidencia de éste en nuestro estudio fue de 59.29%. Conclusiones: Se necesitan más estudios con ketamina nebulizada en vía aérea difícil en la población mexicana, así como una mayor muestra para poder determinar el estándar de oro para el tratamiento del dolor faríngeo postoperatorio.

Abstract: Introduction: The postoperative sore throat is a frequent complication, characterized by odynophagia after endotracheal intubation. Objective: To compare nebulized ketamine in the preoperative period against nebulized placebo for the reduction of the postoperative sore throat on elective surgery under general anesthesia. Material and methods: We performed an experimental, prospective, randomized, double blind study; conducted from February to July 2016. Patients were randomly assigned into two groups: group K: preoperative nebulized ketamine (50 mg: 1 mL of ketamine + 2 mL of saline solution 0.9%) against group P: placebo (nebulization of 3 mL saline solution 0.9%). We collected vital signs as well as symptoms and intensity of postoperative sore throat according to the analog numeric scale at the first and forth postoperative hours. Results: The use of nebulized ketamine does not represent a statistically significant difference compared to placebo for postoperative sore throat. The incidence of postoperative sore throat in our study was of 59.29%. Conclusions: We need further studies of nebulized ketamine in the Mexican population, as well as a larger study to determine the gold standard for the treatment of POST.

The interplay of demography and selection during maize domestication and expansion.

BACKGROUND: The history of maize has been characterized by major demographic events, including population size changes associated with domestication and range expansion, and gene flow with wild relatives. The interplay between demographic history and selection has shaped diversity across maize populations and genomes. RESULTS: We investigate these processes using high-depth resequencing data from 31 maize landraces spanning the pre-Columbian distribution of maize, and four wild teosinte individuals (Zea mays ssp. parviglumis). Genome-wide demographic analyses reveal that maize experienced pronounced declines in effective population size due to both a protracted domestication bottleneck and serial founder effects during post-domestication spread, while parviglumis in the Balsas River Valley experienced population growth. The domestication bottleneck and subsequent spread led to an increase in deleterious alleles in the domesticate compared to the wild progenitor. This cost is particularly pronounced in Andean maize, which has experienced a more dramatic founder event compared to other maize populations. Additionally, we detect introgression from the wild teosinte Zea mays ssp. mexicana into maize in the highlands of Mexico, Guatemala, and the southwestern USA, which reduces the prevalence of deleterious alleles likely due to the higher long-term effective population size of teosinte. CONCLUSIONS: These findings underscore the strong interaction between historical demography and the efficiency of selection and illustrate how domesticated species are particularly useful for understanding these processes. The landscape of deleterious alleles and therefore evolutionary potential is clearly influenced by recent demography, a factor that could bear importantly on many species that have experienced recent demographic shifts.

Capillary blood collected on volumetric absorptive microsampling (VAMS) device for monitoring hydroxychloroquine in rheumatoid arthritis patients.

A novel technique for collection of capillary blood, termed volumetric absorptive microsampling (VAMS), has been recently cleared by the FDA for collection of human blood. VAMS absorbs a fixed volume of blood (10µl) and overcomes area bias and homogeneity issues associated with dried blood spot (DBS). This study is the application of VAMS for therapeutic drug monitoring (TDM) in human capillary blood. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow for analysis of VAMS sample was developed and validated. Concentration of hydroxychloroquine (HCQ) and its metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), in capillary blood on VAMS sampler were compared to those in venous blood in rheumatoid arthritis patients. Feasibility of capillary blood collected on both VAMS and DBS card were evaluated on patients. Stability of dried capillary blood on VAMS was also examined. Our results established that VAMS is a simple and accurate sampling technique that delivers the benefits of DBS sampling while overcoming the issues associated with hematocrit and homogeneity. It requires a small blood volume, simplifies sample logistics management, and may allow sample collection in the patient's home setting.

Validation of a multi-analyte panel with cell-bound complement activation products for systemic lupus erythematosus.

BACKGROUND: We describe the analytical validation of an assay panel intended to assist clinicians with the diagnosis of systemic lupus erythematosus (SLE). The multi-analyte panel includes quantitative assessment of complement activation and measurement of autoantibodies. METHODS: The levels of the complement split product C4d bound to erythrocytes (EC4d) and B-lymphocytes (BC4d) (expressed as mean fluorescence intensity [MFI]) are measured by quantitative flow cytometry, while autoantibodies (inclusive of antinuclear and anti-double stranded DNA antibodies) are determined by immunoassays. Results of the multi-analyte panel are reported as positive or negative based on a 2-tiered index score. Post-phlebotomy stability of EC4d and BC4d in EDTA-anticoagulated blood is determined using specimens collected from patients with SLE and normal donors. Three-level C4 coated positive beads are run daily as controls. Analytical validity is reported using intra-day and inter-day coefficient of variation (CV). RESULTS: EC4d and BC4d are stable for 2days at ambient temperature and for 4days at 4°C post-phlebotomy. Median intra-day and inter-day CV range from 2.9% to 7.8% (n=30) and 7.3% to 12.4% (n=66), respectively. The 2-tiered index score is reproducible over 4 consecutive daysupon storage of blood at 4°C. A total of 2,888 three-level quality control data were collected from 6 flow cytometers with an overall failure rate below 3%. Median EC4d level is 6 net MFI (Interquartile [IQ] range 4-9 net MFI) and median BC4d is 18 net MFI (IQ range 13-27 net MFI) among 86,852 specimens submitted for testing. The incidence of 2-tiered positive test results is 13.4%. CONCLUSION: We have established the analytical validity of a multi-analyte assay panel for SLE.

Performance Characteristics of Different Anti-Double-Stranded DNA Antibody Assays in the Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: We sought to evaluate different anti-double-stranded DNA assays for their performance characteristics in monitoring disease activity fluctuations in systemic lupus erythematosus (SLE). METHODS: 36 active SLE patients were followed monthly. At each study visit (total n = 371), blood was collected and disease activity was scored using the SELENA-SLEDAI (excluding anti-dsDNA or complement components) and by a physician's global assessment (PGA). Four anti-dsDNA tests were compared. Linear mixed-effects models with random intercept and fixed slopes were used to evaluate the relationship between the longitudinal fluctuations of disease activity and anti-dsDNA titers. RESULTS: At enrollment, positivity for QUANTA Lite and high-avidity anti-dsDNA assay was both 64% and significantly lower than anti-dsDNA positivity by QUANTA Flash (83%) and CLIFT (96%). Linear mixed-effects modeling indicated that the change in clinical SELENA-SLEDAI scores was associated with the titers of all anti-dsDNA with QUANTA Flash yielding the highest marginal R2 (0.15; p < 0.01). QUANTA Flash was the only anti-dsDNA assay significantly associated with the change in PGA (marginal R2 = 0.05; p < 0.01). CONCLUSION: These data indicate that anti-dsDNA antibodies determined by QUANTA Flash have a value in monitoring SLE disease activity.

Detection of anti-dsDNA antibodies by computer-aided automated immunofluorescence analysis.

INTRODUCTION: NOVA View is a computer aided fluorescence microscope that is used for the automated reading and interpretation of indirect immunofluorescent tests in diagnostic immunology. The objective of the present study was to evaluate the performance of the NOVA View® system for the measurement of anti-dsDNA antibodies using the Crithidia luciliae indirect immunofluorescence test (CLIFT) technology. METHODS: Analytical performance of NOVA View CLIFT was assessed in repeatability (within run) and reproducibility (between runs and instruments) studies. Two hundred-fifty patient samples (N=200 consecutive samples and N=50 samples from systemic lupus erythematosus patients) were tested to evaluate the agreement between results generated with NOVA View CLIFT, and those obtained with manual microscopic reading of the same slides. Positivity rate in SLE was assessed on the 50 SLE samples. RESULTS: The NOVA View system showed high level of repeatability and reproducibility within runs, between runs, and between instruments. Agreement of NOVA View software interpretation and digital image reading results with manual microscopic reading results was 96.0%, and the same positivity rate was obtained on SLE samples by NOVA View digital image reading as that of manual microscopic reading (36.0% vs. 38.0%, respectively). CONCLUSION: Results generated by NOVA View CLIFT were equivalent to those obtained by manual microscopic reading on a large routine sample set. NOVA View demonstrated consistency within and between runs, and between instruments. Automation of CLIFT provides reliability and is a suitable alternative for routine clinical laboratories.

Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements.

OBJECTIVE: To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE). METHODS: The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity. RESULTS: AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03). CONCLUSIONS: CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.

Megabase-scale inversion polymorphism in the wild ancestor of maize.

Chromosomal inversions are thought to play a special role in local adaptation, through dramatic suppression of recombination, which favors the maintenance of locally adapted alleles. However, relatively few inversions have been characterized in population genomic data. On the basis of single-nucleotide polymorphism (SNP) genotyping across a large panel of Zea mays, we have identified an ∼50-Mb region on the short arm of chromosome 1 where patterns of polymorphism are highly consistent with a polymorphic paracentric inversion that captures >700 genes. Comparison to other taxa in Zea and Tripsacum suggests that the derived, inverted state is present only in the wild Z. mays subspecies parviglumis and mexicana and is completely absent in domesticated maize. Patterns of polymorphism suggest that the inversion is ancient and geographically widespread in parviglumis. Cytological screens find little evidence for inversion loops, suggesting that inversion heterozygotes may suffer few crossover-induced fitness consequences. The inversion polymorphism shows evidence of adaptive evolution, including a strong altitudinal cline, a statistical association with environmental variables and phenotypic traits, and a skewed haplotype frequency spectrum for inverted alleles.

Desarrollo de un software educativo para enfermeria del adulto: modelos de análisis y diseño / Development of educational software for adult nursing: an analysis models and designs or

Este trabajo muestra el proceso que se siguió para realizar los modelos de análisis y diseño necesarios para desarrollar un producto de hipermedia, aplicable en el pregrado de Enfermería en el ámbito universitario. Se describen los pasos llevados a cabo para el desarrollo del software. La aplicación del Proceso Unificado de Racional, que se utilizó en este caso, garantiza estándares de calidad y asegura el éxito del proyecto.