Population risk factors for nulliparous, term, singleton, vertex caesarean birth: a national cross-sectional study.

OBJECTIVE: To characterise medical, obstetric and demographic risk factors associated with nulliparous, term, singleton, vertex (NTSV) caesarean birth. STUDY DESIGN: Cross-sectional study. SETTING: United States delivery hospitalisations. POPULATION: NTSV births in 2016-18 US natality data. METHODS: This study analysed a national sample of natality data generated by the United States National Vital Statistics System. NTSV deliveries were identified. The primary outcome was caesarean birth. Risk factors including maternal age, body mass index (BMI) and pregestational diabetes were analysed. Multivariable log-linear regression models analysed factors associated with NTSV caesarean with adjusted risk ratios (aRR) as measures of effect. RESULTS: Of 11 622 400 deliveries, 3 764 707 met NTSV criteria, and their caesarean section rate was 25.9%. Maternal age 35-39 years (aRR 1.51, 95% CI 1.50-1.52) and 40-54 years (aRR 2.03, 95% 2.00-2.05) compared with age 19-34 years; BMI 25 to <30 kg/m2 (aRR 1.32, 95% CI 1.31-1.33), 30 to <35 kg/m2 (aRR 1.57 95% CI 1.56-1.58), 35 to <40 kg/m2 (aRR 1.82, 95% CI 1.80-1.83) and ≥40 kg/m2 (aRR 2.17, 95% CI 2.15-2.19) compared with BMI 18.5-24.9 kg/m2; and pregestational diabetes (aRR 1.54, 95% CI 1.51-1.57) were all associated with increased risk. Risk factors allowed stratification of patients into high-risk versus low-risk groups. The NTSV caesarean rate was 37.9% in women who had one or more of the following characteristics: age ≥35 years, BMI ≥30 kg/m2 or pregestational diabetes. In comparison, the NTSV caesarean rate was 20.8% among women without any of these three risk factors (P < 0.01). CONCLUSION: Among NTSV births, BMI, maternal age and medical conditions are important risk factors for caesarean delivery.

Radiographic diagnosis of small intestinal obstruction in pet rabbits (Oryctolagus cuniculus): 63 cases.

OBJECTIVES: To identify radiographic features that can be used to aid in the diagnosis of small intestinal obstruction in pet rabbits. MATERIALS AND METHODS: Retrospective study comparing radiographic features of 63 cases of confirmed intestinal obstruction with 50 abdominal radiographs taken of rabbits without gastrointestinal disease. Abdominal radiographs were examined for gastric size, gastric contents, small intestinal dilatation and gas within the large intestine and caecum. RESULTS: Gastric size, gastric contents, small intestinal dilatation and gas within the large intestine and caecum were all features that differed between rabbits with small intestinal obstruction and rabbits without gastrointestinal disease. Radiographic features associated with small intestinal obstruction included severe gastric dilation, gastric contents primarily consisting of liquid and gas, small intestinal dilation and absence of large amounts of gas in the caecum and large intestine. CLINICAL SIGNIFICANCE: Observation on gastric size, small intestinal dilatation and gas within the large intestine and caecum aid in radiological diagnosis of small intestinal obstruction in rabbits and so can guide appropriate treatment.

Osseous versus Nonosseous Spinal Epidural Arteriovenous Fistulas: Experiences of 13 Patients.

BACKGROUND AND PURPOSE: Spinal epidural arteriovenous fistulas are rare vascular malformations. We present 13 patients with spinal epidural arteriovenous fistulas, noting the various presenting symptom patterns, imaging findings related to bone involvement, and outcomes. MATERIALS AND METHODS: Among 111 patients with spinal vascular malformations in the institutional data base from 1993 to 2017, thirteen patients (11.7%) had spinal epidural arteriovenous fistulas. We evaluated presenting symptoms and imaging findings, including bone involvement and mode of treatment. To assess the treatment outcome, we compared initial and follow-up clinical status using the modified Aminoff and Logue Scale of Disability and the modified Rankin Scale. RESULTS: The presenting symptoms were lower back pain (n = 2), radiculopathy (n = 5), and myelopathy (n = 7). There is overlap of symptoms in 1 patient (No. 11). Distribution of spinal epidural arteriovenous fistulas was cervical (n = 3), thoracic (n = 2), lumbar (n = 6), and sacral (n = 2). Intradural venous reflux was identified in 7 patients with congestive venous myelopathy. The fistulas were successfully treated in all patients who underwent treatment (endovascular embolization, n = 10; operation, n = 1) except 2 patients who refused treatment due to tolerable symptoms. Transarterial glue (n = 7) was used in nonosseous types; and transvenous coils (n = 3), in osseous type. After 19 months of median follow-up, the patients showed symptom improvement after treatment. CONCLUSIONS: Although presenting symptoms were diverse, myelopathy caused by intradural venous reflux was the main target of treatment. Endovascular treatment was considered via an arterial approach in nonosseous types and via a venous approach in osseous types.

Cannulation of Occluded Inferior Petrosal Sinuses for the Transvenous Embolization of Cavernous Sinus Dural Arteriovenous Fistulas: Usefulness of a Frontier-Wire Probing Technique.

BACKGROUND AND PURPOSE: Pursuing an alternative access route for transvenous embolization of cavernous sinus dural arteriovenous fistulas can be challenging in patients with an occluded inferior petrosal sinus. We found that cannulation of even a completely occluded inferior petrosal sinus is feasible, especially when using a standard hydrophilic-polymer-jacketed 0.035-inch guidewire as a frontier-wire for probing. MATERIALS AND METHODS: From 2002 to 2017, the frontier-wire technique was tried in 52 patients with occluded inferior petrosal sinuses for transvenous embolization of cavernous sinus dural arteriovenous fistulas at our center. Technical success was defined as access into the affected cavernous sinus compartment with a microcatheter through the occluded inferior petrosal sinus and deployment of at least 1 coil. The complications and treatment outcomes were analyzed. RESULTS: The frontier-wire technique was applied in 52 patients with 57 occluded inferior petrosal sinuses (52 ipsilateral and 5 contralateral inferior petrosal sinuses). Technical success rates were 80.8% (42/52) of patients and 73.7% (42/57) of inferior petrosal sinuses. Alternative transvenous routes were used in 3 patients, and transarterial access was used in 7 patients. Complete embolization of fistulas was achieved in 82.2% (37/45) of patients in the transvenous embolization group and in 14.3% (1/7) of patients in the transarterial group. No procedure-related morbidity or mortality was observed. CONCLUSIONS: Transvenous embolization of cavernous sinus dural arteriovenous fistulas, even through a completely occluded inferior petrosal sinus, is feasible. The difficulty of passing the microcatheter can be minimized by prior probing of the occluded inferior petrosal sinus using a standard 0.035-inch guidewire; the trace of the guidewire on the roadmap image serves as a guide for microcatheter navigation through the inferior petrosal sinus on fluoroscopy.

Evaluation of fracture resistance of ceramic veneers with different preparation designs and loading conditions: An in vitro study.

PURPOSE: The purpose of this study was to evaluate the effect of incisal butt joint and incisal overlap design on the fracture resistance of ceramic veneers under two different loading conditions, i.e., 125° and 60° representing protrusive and intercuspal movements, respectively. MATERIALS AND METHODS: Thirty-two maxillary central incisors were divided into two groups of sixteen specimens each and were prepared with incisal butt joint and incisal overlap design. Ceramic veneers were fabricated and cemented. Both the groups were further divided and mechanical testing to evaluate the fracture resistance were done using the universal testing machine. The values were recorded in Newton along with the assessment of the failure mode of both veneer and the tooth. RESULTS: Unpaired t-test showed a significant difference (P < 0.05) with butt joint design having higher fracture resistance than palatal overlap design with the mean value of 409.50N at 60° angle and 473.37N at 125° angle. Paired t-test depicted a significant difference for both the designs at 125° than at 60° angle (P < 0.05). Chi-square analysis showed more number of intact veneers with butt joint design; however, there was no significant difference (P > 0.05). Failure mode of teeth showed more number of coronal fracture followed by cervical fracture and root fracture, but there was no significant difference between the two groups (P > 0.05). CONCLUSION: Butt joint design had higher fracture resistance than palatal overlap design. Under functional loads for both designs, fracture resistance was higher at 125° than at 60° angle.

Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension.

Glucocorticoids are administered to premature infants to accelerate pulmonary maturation. In experimental model, prenatal dexamethasone (DEX) results in reduced nephron number and adulthood hypertension. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), can cause oxidative stress and is involved in the development of hypertension. L-citrulline can be converted to l-arginine (the substrate for NOS) in the body. Thus we intended to determine if maternal L-citrulline therapy can prevent prenatal DEX-induced programmed hypertension by restoration ADMA/nitric oxide (NO) balance, alterations of renin-angiotensin system (RAS) and sodium transporters, and epigenetic regulation by histone deacetylases (HDACs). Male offspring were assigned to four groups: control, pregnancy rats received intraperitoneal DEX (0.2 mg/kg body weight) daily on gestational days 15 and 16 (DEX), pregnancy rats received 0.25% L-citrulline in drinking water during the entire pregnancy and lactation period (CIT), and DEX + CIT. We found DEX group developed hypertension at 16 weeks of age, which was prevented by maternal L-citrulline therapy. Prenatal DEX exposure increased plasma ADMA concentrations and reduced renal NO production. However, L-citrulline reduced plasma ADMA level and increased renal level of NO in DEX + CIT group. Next, prenatal DEX-induced programmed hypertension is related to increased mRNA expression of angiotensin and angiotensin II type 1 receptor, and class I HDACs in the kidney. Prenatal DEX exposure increased renal protein abundance of Na(+)/Cl(-) cotransporter (NCC), which was prevented by L-citrulline therapy. The beneficial effects of L-citrulline therapy include restoration of ADMA/NO balance and alteration of NCC, to prevent the prenatal DEX-induced programmed hypertension.

Stem cell signaling in immunity and development.

Stem cells in the shoot apical meristem (SAM) of plants are the self-renewable reservoir for leaf, stem, and flower organogenesis. Stem-cell fate and population size are subject to regulation by complex intrinsic signals and environmental cues to ensure balanced plant development, survival, and longevity. Peptides secreted from the shoot stem cells have pivotal roles in controlling cell identity, proliferation, and differentiation through multiple receptor kinase complexes. The best-characterized in vivo and in vitro peptide ligands are the 12-amino acid (aa) and the arabinosylated 13-aa CLAVATA3 peptides (CLV3p) that are perceived by multiple receptors with partially overlapping and distinct expression patterns and functions in the SAM. The primary molecular and cellular signaling mechanisms after the occurrence of ligand-receptor interaction remain elusive. Integrated analyses provide novel evidence for differential peptide-receptor signaling in the dynamic regulation of stem-cell homeostasis and fitness. Surprisingly, the 12-aa CLV3p can trigger immune signaling and limit pathogen invasion via the flagellin receptor kinase FLS2, suggesting a previously unrecognized molecular mechanism underlying enhanced immunity in the SAM area. Because pattern recognition receptor signaling in immune responses also profoundly intercepts plant development, peptide-receptor kinase signaling in immunity and development may share a common evolutionary origin.

Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia.

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

Nail changes associated with chemotherapy in children.

BACKGROUND: Large series of chemotherapy-induced nail changes in children have rarely been reported in the literature. OBJECTIVE: To study the pattern and onset of nail changes in cancer children receiving various chemotherapy regimens. METHODS: A cross-sectional study was performed on 30 paediatric patients (aged 1-17, mean 8.3 years), including 11 with acute lymphoblastic leukaemia, five with acute myeloid leukaemia, and others. RESULTS: Nail changes developed in 10 children during chemotherapy, five of whom had Muehrcke's lines, three Beau's lines, one Mees' lines and another had trachyonychia. There appeared to be no correlation between the pattern of nail alteration and the underlying cancer types or stages, or the regimens of chemotherapy. CONCLUSION: One third of the children with cancers developed nail changes associated with chemotherapy. Among them, Muehrcke's lines were the most common manifestation, which were unrelated to hypoalbuminaemia in our series.

Sugar sensing and signalling networks in plants.

Plant sugar signalling operates in a complex network with plant-specific hormone signalling pathways. Hexokinase was identified as an evolutionarily conserved glucose sensor that integrates light, hormone and nutrient signalling to control plant growth and development.

Analysis of neutral drugs in human plasma by fluoride attachment in liquid chromatography/negative ion electrospray tandem mass spectrometry.

The analysis of several neutral drugs, mephenesin, guaifenesin, simvastatin, podophyllotoxin and inositol, was accomplished by negative ion electrospray ionization mass spectrometry (ESI-MS) using adduct formation with three different halide ions. The fluoride, chloride and bromide adducts of the selected drugs exhibited intense signals in negative ion ESI. Under collision-induced dissociation, the major product ions of bromide and chloride adducts were the nonspecific bromide and chloride anions, respectively. In contrast, fluoride adducts produced strong [M--H](-) ions as well as product ions with good intensity. Fluoride attachment liquid chromatography/negative ion electrospray tandem mass spectrometry (LC/ESI-MS/MS) was applied to the analysis of the selected neutral drugs in human plasma. Detection limits in the range of 0.025-0.05 ng/mL were achieved using 0.5 mL plasma. Good linearity was observed for each of the drugs examined in human plasma over the range of 0.05-50 ng/mL.

Application of pentafluorophenyl hydrazine derivatives to the analysis of nabumetone and testosterone in human plasma by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

Two carbonyl compounds, nabumetone and testosterone, were derivatized with pentafluorophenyl hydrazine (PFPH) and analyzed by atmospheric-pressure chemical-ionization mass spectrometry. The PFPH derivatives underwent dissociative electron capture in negative-ion APCI (ECAPCI) and gave intense [M-20](-) ions in the mass spectra. In positive-ion APCI, the PFPH derivatives underwent efficient protonation and gave intense [M + H](+) ions in the mass spectra. In CID, the major product ions of the [M-20](-) ions in ECAPCI corresponded to the partial moiety of PFPH. In contrast, the major product ions of [M + H](+) corresponded to the partial moiety of the analyte. By using selected reaction monitoring (SRM) detection, low pg of nabumetone (1 pg) and testosterone (7 pg) could be detected in both ECAPCI and positive-ion APCI. In comparison with the detection limits (SRM) of the underivatized analytes, use of the PFPH derivatives resulted in 2500-fold and 35-fold sensitivity enhancements for nabumetone and testosterone, respectively. The PFPH derivatives were applied to the analysis of nabumetone and testosterone in human plasma by both ECAPCI and positive-ion APCI and were found to enable detection of 0.1 ng mL(-1) nabumetone in spiked plasma. For testosterone, endogenous testosterone in female plasma was detected in both ECAPCI and positive-ion APCI.

c-Myc alters the DNA damage-induced G2/M arrest in human mammary epithelial cells.

Effects of c-Myc overexpression on the DNA damage-induced G2/M checkpoint were studied in finite lifespan, normal human mammary epithelial cells (HMECs). Previously, we showed that c-Myc attenuates G1/S arrest and leads to an inappropriate entry of cells with damaged DNA into the S phase, following treatment with ionising radiation (IR). Here we show that, in striking contrast to control cells, c-Myc-overexpressing HMECs demonstrate a significant attenuation of the G2/M arrest, following IR, and enter into inappropriate mitoses. At the molecular level, ectopic overexpression of c-Myc leads to an unusually high level of expression of cyclin B1, and the elevated levels of cyclin B1 were maintained, after gamma-irradiation. Introduction of DNA damage in c-Myc-overexpressing, normal mammary epithelial cells eventually induces apoptosis, indicating a dramatic sensitisation by c-Myc of DNA damage-induced apoptosis. These two remarkable phenotypes, checkpoint attenuation and sensitisation to apoptosis, resulting from a deregulation of the protooncogene c-myc, may produce a unique pattern of alternating cycles, consisting first of amplification of DNA damage, followed by apoptosis-assisted selective pressure. The result of this alternating pattern of damage apoptosis could facilitate the selection of certain genomic alterations required for cellular survival and cellular transformation.

Lambda spectra in 11.6A GeV/c Au-Au collisions.

E896 has measured Lambda production in 11.6A GeV/c Au-Au collisions over virtually the whole rapidity phase space. The midrapidity p(t) distributions have been measured for the first time at this energy and appear to indicate that the Lambda hyperons have different freeze-out conditions than protons. A comparison with the relativistic quantum molecular dynamics model shows that while there is good shape agreement at high rapidity the model predicts significantly different slopes of the m(t) spectra at midrapidity. The data, where overlap occurs, are consistent with previously reported measurements.

Signal transduction in maize and Arabidopsis mesophyll protoplasts.

Plant protoplasts show physiological perceptions and responses to hormones, metabolites, environmental cues, and pathogen-derived elicitors, similar to cell-autonomous responses in intact tissues and plants. The development of defined protoplast transient expression systems for high-throughput screening and systematic characterization of gene functions has greatly contributed to elucidating plant signal transduction pathways, in combination with genetic, genomic, and transgenic approaches.

Dissection of abscisic acid signal transduction pathways in barley aleurone layers.

Abscisic acid (ABA) induces genes that are highly expressed during late embryogenesis, but suppresses gibberellin (GA)-responsive genes essential for seed germination and seedling growth. Promoter elements necessary and sufficient for ABA up- and down-regulation of gene expression have been previously defined in barley aleurone layers. We have studied the effect of a protein phosphatase 2C, ABI1, an ABA-inducible protein kinase, PKABA1, and a transcription factor, VP1, on ABA action in a barley aleurone transient expression system. The observations have allowed us to dissect ABA signal transduction pathways leading to either induction or suppression of gene expression. The ABA induction of embryogenesis genes is highly inhibited in the presence of a mutated protein phosphatase 2C, encoded by the abi1-1 dominant mutant gene that is known to block ABA responses in Arabidopsis. However, the abi1-1 gene product has no effect on the ABA suppression of a GA-responsive alpha-amylase gene. On the other hand, PKABA1 suppresses the expression of alpha-amylase genes, but has little effect on ABA up-regulated genes. Therefore, it appears that ABA induction and suppression follow two separate signal transduction pathways with the former inhibited by ABI1 and the latter modulated by PKABA1. The presence of VP1 enhances the ABA induction of late embryogenesis genes, but also suppresses germination specific genes. A schematic model based on these observations is presented to explain the effect of these regulatory proteins on ABA-mediated gene expression.

Plant mitogen-activated protein kinase signaling cascades.

Mitogen-activated protein kinase (MAPK) cascades have emerged as a universal signal transduction mechanism that connects diverse receptors/sensors to cellular and nuclear responses in eukaryotes. Recent studies in plants indicate that MAPK cascades are vital to fundamental physiological functions involved in hormonal responses, cell cycle regulation, abiotic stress signaling, and defense mechanisms. New findings have revealed the complexity and redundancy of the signaling components, the antagonistic nature of distinct pathways, and the use of both positive and negative regulatory mechanisms.

Two-component circuitry in Arabidopsis cytokinin signal transduction.

Cytokinins are essential plant hormones that are involved in shoot meristem and leaf formation, cell division, chloroplast biogenesis and senescence. Although hybrid histidine protein kinases have been implicated in cytokinin perception in Arabidopsis, the action of histidine protein kinase receptors and the downstream signalling pathway has not been elucidated to date. Here we identify a eukaryotic two-component signalling circuit that initiates cytokinin signalling through distinct hybrid histidine protein kinase activities at the plasma membrane. Histidine phosphotransmitters act as signalling shuttles between the cytoplasm and nucleus in a cytokinin-dependent manner. The short signalling circuit reaches the nuclear target genes by enabling nuclear response regulators ARR1, ARR2 and ARR10 as transcription activators. The cytokinin-inducible ARR4, ARR5, ARR6 and ARR7 genes encode transcription repressors that mediate a negative feedback loop in cytokinin signalling. Ectopic expression in transgenic Arabidopsis of ARR2, the rate-limiting factor in the response to cytokinin, is sufficient to mimic cytokinin in promoting shoot meristem proliferation and leaf differentiation, and in delaying leaf senescence.

Molecular identification of phenylalanine ammonia-lyase as a substrate of a specific constitutively active Arabidopsis CDPK expressed in maize protoplasts.

Phenylalanine ammonia-lyase (PAL) is a key enzyme in pathogen defence, stress response and secondary metabolism and is subject to post-translational phosphorylation. In order to address the significance of this phenomenon it is necessary to identify the protein kinase (PK) responsible and place it in its regulatory circuit. Using protoplast transient expression of Arabidopsis kinase genes coupled to immunocomplex kinase assay, it has been possible to screen for specific PAL kinase. We show here that AtCPK1 (calcium dependent PK), but not other closely related PKs could phosphorylate both a recombinant PAL protein and a peptide (SRVAKTRTLTTA) that is a site phosphorylated in vivo. Identification of the specific CDPK as a PAL kinase now opens up the possibility of exploring the calcium link in biotic stress signalling, salicylate and phytoalexin production as well as the significance of PAL phosphorylation. The protoplast transient expression system is a potentially powerful method to determine and screen for plant gene functions utilising genomic and proteomic data.

Mesophyll-specific, light and metabolic regulation of the C4 PPCZm1 promoter in transgenic maize.

To play an essential role in C4 photosynthesis, the maize C4 phosphoenolpyruvate carboxylase gene (PPCZm1) acquired many new expression features, such as leaf specificity, mesophyll specificity, light inducibility and high activity, that distinguish the unique C4 PPC from numerous non-C4 PPC genes in maize. We present here the first investigation of the developmental, cell-specific, light and metabolic regulation of the homologous C4 PPCZm1 promoter in stable transgenic maize plants. We demonstrate that the 1.7 kb of the 5'-flanking region of the PPCZm1 gene is sufficient to direct the C4-specific expression patterns of beta-glucuronidase (GUS) activity, as a reporter, in stable transformed maize plants. In light-grown shoots, GUS expression was strongest in all developing and mature mesophyll cells in the leaf, collar and sheath. GUS activity was also detected in mesophyll cells in the outer husks of ear shoots and in the outer glumes of staminate spikelets. We did not observe histological localization of GUS activity in light- or dark-grown callus, roots, silk, developing or mature kernels, the shoot apex, prop roots, or pollen. In addition, we used the stable expressing transformants to conduct and quantify physiological induction studies. Our results indicate that the expression of the C4 PPCZm1-GUS fusion gene is mesophyll-specific and influenced by development, light, glucose, acetate and chloroplast biogenesis in transgenic maize plants. These studies suggest that the adoption of DNA regulatory elements for C4-specific gene expression is a crucial step in C4 gene evolution.