Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes.

BACKGROUND: Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls. METHODS: Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses. RESULTS: A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25. CONCLUSIONS: In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.

Association of Maternal Versus Fetal Ehlers-Danlos Syndrome Status with Poor Pregnancy Outcomes.

The majority of research papers published on obstetrical outcomes in Ehlers-Danlos syndrome (EDS) have focused on the contribution of maternal EDS to the risk of poor pregnancy outcomes. The purpose of our study was to further clarify the fetal versus maternal contribution of EDS to poor pregnancy outcomes. A web-based, anonymous questionnaire was developed to collect pregnancy histories of families with a member with EDS. The survey was disseminated via social media through the Ehlers Danlos National Foundation. Population descriptors (age, gender, EDS diagnosis, age of diagnosis) and pregnancy descriptors (number of pregnancies, live births, and birth complications) were collected. To identify fetal and maternal contribution of EDS to poor pregnancy outcomes, three groups were compared based on maternal or infant diagnosis (EDS versus non-EDS). The rate of birth complications, treatment for preterm birth, and occurrence of preterm birth, as well as gestational age at preterm birth, were different depending on maternal/ infant EDS status, and these differences were significant when comparing infant EDS status but not when comparing maternal EDS status. The occurrence of PPROM is increased in the non-EDS mother/EDS infant group compared to both EDS mother/non-EDS infant and EDS mother/EDS infant groups (38.9%, 12.5%, 14.8%, p = 0.025). This study identifies that poor outcomes in EDS pregnancies differ depending on the maternal and the fetal EDS status. These insights into maternal and fetal association with certain poor pregnancy outcomes in pregnancies complicated by EDS can further guide physicians in educating, managing, and treating these women during pregnancy.

[Update on endocrine hypertension]. / Update endokrine Hypertonie.

Endocrine disorders are the most common causes of secondary hypertension. Early diagnosis and specific treatment are crucial for improvement of the prognosis. This article provides an overview on which clinical constellations point to an increased risk of secondary causes of hypertension. These include spontaneous hypokalemia, young age at onset of hypertension, adrenal incidentaloma and therapy refractive arterial hypertension. The basic diagnostics include determination of the aldosterone to renin ratio, measurement of free plasma metanephrines and a 1 mg dexamethasone suppression test. Borderline results require repeated control testing and/or confirmatory testing under standardized test conditions. In cases of repeatedly conspicuous results referral to a specialized clinic should be considered for further clarification and confirmation of the diagnosis. Imaging diagnostics may constitute an adjunct to laboratory testing after the diagnosis has been confirmed. Therapeutic algorithms vary depending on the underlying endocrine disease.

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

INTRODUCTION: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. METHODS: Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. RESULTS: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. CONCLUSIONS: Ondansetron rdf is effective for the prophylaxis of rinv.

End-of-life care in a regional level IV neonatal intensive care unit after implementation of a palliative care initiative.

OBJECTIVE: We hypothesized that the implementation of a neonatal palliative care initiative will result in improved markers of end-of-life care. STUDY DESIGN: A retrospective and prospective chart review of neonatal intensive care unit deaths was performed for 24 months before, 16 months during and 24 months after the implementation of palliative care provider education and practice guidelines (n=106). Ancillary care, redirection of care, palliative medication usage and outcome meetings in the last 48 h of life and basic demographic data were compared between epochs. Parametric and nonparametric analysis was performed. RESULT: There was an increase in redirection of care and palliative medication usage and a decrease in variability of use of end-of-life interventions (P=0.012, 0.022 and <0.001). CONCLUSION: The implementation of a neonatal palliative care initiative was associated with increases in palliative interventions for neonates in their final 48 h of life, suggesting that such an initiative may enhance end-of-life care.

Experimental observation of defect pair separation triggering phase transitions.

First-order phase transitions typically exhibit a significant hysteresis resulting for instance in boiling retardation and supercooling. The hysteresis arises, because nucleation of the new phase is activated. The free-energy change is positive until the nucleus reaches a critical size beyond which further growth is downhill. In practice, the barrier is often circumvented by the presence of heterogeneous nucleation centres, e.g. at vessel walls or seed crystals. Recently, it has been proposed that the homogeneous melting of ice proceeds via separation of defect pairs with a substantially smaller barrier as compared to the mere aggregation of defects. Here we report the observation of an analogous mechanism catalysing a two-dimensional homogeneous phase transition. A similar process is believed to occur in spin systems. This suggests that separation of defect pairs is a common trigger for phase transitions. Partially circumventing the activation barrier it reduces the hysteresis and may promote fluctuations within a temperature range increasing with decreasing dimensionality.

Atomic scale friction of molecular adsorbates during diffusion.

Experimental observations suggest that molecular adsorbates exhibit a larger friction coefficient than atomic species of comparable mass, yet the origin of this increased friction is not well understood. We present a study of the microscopic origins of friction experienced by molecular adsorbates during surface diffusion. Helium spin-echo measurements of a range of five-membered aromatic molecules, cyclopentadienyl, pyrrole, and thiophene, on a copper(111) surface are compared with molecular dynamics simulations of the respective systems. The adsorbates have different chemical interactions with the surface and differ in bonding geometry, yet the measurements show that the friction is greater than 2 ps(-1) for all these molecules. We demonstrate that the internal and external degrees of freedom of these adsorbate species are a key factor in the underlying microscopic processes and identify the rotation modes as the ones contributing most to the total measured friction coefficient.

Note: a new design for a low-temperature high-intensity helium beam source.

A high-intensity supersonic beam source is a key component of any atom scattering instrument, affecting the sensitivity and energy resolution of the experiment. We present a new design for a source which can operate at temperatures as low as 11.8 K, corresponding to a beam energy of 2.5 meV. The new source improves the resolution of the Cambridge helium spin-echo spectrometer by a factor of 5.5, thus extending the accessible timescales into the nanosecond range. We describe the design of the new source and discuss experiments characterizing its performance. Spin-echo measurements of benzene/Cu(100) illustrate its merit in the study of a typical slow-moving molecular adsorbate species.

Weak intermolecular interactions in an ionically bound molecular adsorbate: cyclopentadienyl/Cu(111).

The dissociative adsorption of cyclopentadiene (C(5)H(6)) on Cu(111) yields a cyclopentadienyl (Cp) species with strongly anionic characteristics. The Cp potential energy surface and frictional coupling to the substrate are determined from measurements of dynamics of the molecule together with density functional calculations. The molecule is shown to occupy degenerate threefold adsorption sites and molecular motion is characterized by a low diffusional energy barrier of 40±3 meV with strong frictional dissipation. Repulsive dipole-dipole interactions are not detected despite charge transfer from substrate to adsorbate.

Possible significance of advanced glycation end products in serum in end-stage renal disease and in late complications of diabetes.

Advanced glycation end products were determined immunologically in blood from diabetics, patients with renal failure and subjects with various other diseases. Elevation of advanced glycation end products levels in serum is not confined to the diabetic state but was also observed in some severely ill subjects. Patients with end-stage renal disease on dialysis displayed high advanced glycation end products levels in serum, irrespective of the presence or absence of diabetes. In contrast, advanced glycation end products levels in uraemic subjects not treated by dialysis were not different from controls. In diabetics, levels of advanced glycation end products were related to the state of late complications. Diabetics without sequelae showed advanced glycation end products within the normal range, whereas in the presence of late complications mean advanced glycation end products levels were elevated. In the case of retinopathy the increase in advanced glycation end products was associated with the severity of retinal status.

Immunological determination of advanced glycosylation end-products in human blood and urine.

Advanced glycosylation end-products (AGE) in human blood and urine were investigated with the aid of an AGE-specific enzyme-linked immunosorbent assay. Evidence is presented that AGE are natural constituents of human serum and urine. In diabetics with normal renal function only a small increase in serum AGE levels was found as compared to normal controls, while no difference in urinary excretion rate was discernible. Urinary excretion rate of AGE from diabetic and non-diabetic patients with end-stage renal disease was reduced, while high serum AGE levels were observed. AGE in serum occur in a low-molecular-weight fraction and in a possibly protein-bound high-molecular-weight fraction. In urine from normal controls three immunologically reactive fractions were detected whose apparent molecular mass ranged from 100 to 1000 Daltons, while in urine from patients with end-stage renal failure additional high-molecular-weight fractions appeared.

[Secretion of inflammatory cytokines and prostaglandins by fetal trophoblast cells induces uterine contraction and labor onset]. / Die Sekretion inflammatorischer Zytokine bzw. Prostaglandine durch fetale Trophoblastzellen induziert Wehentätigkeit und Geburtsbeginn.

OBJECTIVE: Induce infection-associated cytokines intrauterine secretion of prostaglandins and term labor? METHODS: Concentrations of Il-6, Il-1 beta, TNF-alpha, PGF2 and PGF2 alpha were determined in cervical secretions and amniotic fluid during spontaneous term labor. The supernatant of amnion-, chorion-, decidua- and trophoblast cells, cultured after elective cesarean section or spontaneous delivery, was analysed for cytokine- and prostaglandin activity. RESULTS: Term labor always is associated with intrauterine cytokine- and prostaglandin release. Increased production of cytokines and prostaglandins in case of normal term labor only was found by fetal trophoblast cells. CONCLUSIONS: Signal for parturition is of trophoblast and therefore of fetal origin.

Impaired immunoglobulin G Fc fragment function in diabetics is caused by a mechanism different from glycation.

Glycation and fluorescence at 440 nm (excitation at 370 nm) were found to be increased in immunoglobulin G (IgG) from diabetics, strongly indicating the presence of IgG-linked advanced glycosylation end products. In contrast, levels of IgG-linked advanced glycosylation end products were low or undetectable in both normal and diabetic subjects when an advanced glycosylation end products specific antibody was employed for immunological determination of advanced glycosylation end products. Furthermore, no correlation exists between IgG glycation, fluorescence and immunoreactivity. In diabetics, the Fc fragment of IgG showed decreased protein A binding and decreased fixation of complement. This impairment of biological activity was not correlated with the immunologically determined level of advanced glycosylation end products, whereas IgG-linked fluorescence was inversely related to complement fixing activity. These results indicate that mechanisms different from glycation or browning are responsible for changes in the functional properties of IgG.

The polymorphic pattern of somatomedins during human development.

Human somatomedins (Sm) are heterogeneous on separation by chromatofocussing. Besides the 'classic' insulin-like growth factor I and II (IGF-I/Sm-C and IGF-II), a number of minor peaks emerge which can be classified as IGF-I/Sm-C-like or as IGF-II-like. The aim of the current study was to investigate whether or not polymorphism of somatomedins is present in individuals and whether or not the polymorphic pattern changes during development. Serum extracts from normal healthy children and adults were fractionated by chromatofocussing and the various somatomedin-like peptides were quantitated by specific radioimmunoassays for IGF-I/Sm-C or IGF-II. The results demonstrate 1) that heterogeneity of somatomedins is a common phenomenon existing in all individuals studied, and 2) that the polymorphic patterns of the IGF-I/Sm-C-family and of the IGF-II-family remain rather stable during development, although minor changes are evident.

[Planimetric studies of the behavior of the visual field following glaucoma operations]. / Planimetrische Untersuchungen zum Verhalten des Gesichtsfeldes nach Glaukomoperationen.

This article presents the results of functional investigation of the central and peripheral visual fields of 30 patients 3 years after glaucoma surgery. The authors studied the relationship between intraocular pressure and the site of the visual field, and also between vision and the quality of the central visual field. The results of the investigation support the demand for early surgery in glaucoma cases. Patients should be advised and informed thoroughly, because in 36 percent of all cases the cataract grows postoperatively.

The effects of delayed auditory feedback and masking on the fundamental frequency of stutterers and nonstutterers.

This investigation determined if fluency of the reader or type of auditory feedback changed characteristics of fundamental frequency or duration in oral reading by stutterers or nonstutterers. Mingographic tracings were made of sentences excerpted from tape recordings of paragraphs read by 15 adult male stutterers and 15 adult male nonstutterers in three conditions of feedback: normal auditory feedback (under earphones), delayed auditory feedback (0.14 sec delay), and masking (90 dB SPL). The data included 15 measures of fundamental frequency and two measures of duration. Stutterers read sentences in greater total time and with more downward inflections than nonstutterers. Comparison of the delayed auditory feedback (DAF) conditions with the normal auditory feedback (NAF) condition showed that the numbers of total, upward, and downward inflections and upward pitch shifts increased under DAF. In the DAF condition, average rates of upward and downward inflections decreased, and mean and median fundamental frequencies and total time increased. The only changes from the NAF to the masking condition were increases in mean and median fundamental frequencies.

Clinical comparative evaluation of choline magnesium trisalicylate and acetylsalicylic acid in rheumatoid arthritis.

A multicentre double-blind comparison of choline magnesium trisalicylate (CMT) and acetylsalicylic acid (ACSA) compared the two medications for seven weeks in rheumatoid arthritis patients. Investigators measured the number of painful and swollen joints and the duration of morning stiffness, and assessed the overall condition of each patient. Both medications were highly effective in significantly reducing the severity of symptoms flaring after interruption of prior therapy. CMT achieved a greater reduction in the number of swollen joints than did ACSA (P less than 0.05). The incidence of adverse side-effects per patient was significantly less with CMT (P less than 0.05) (ACSA 32.1%; CMT, 16.3%. A larger percentage of ACSA patients (50.8%) reported adverse side-effects than did CMT patients 28.4%) (P less than 0.02).