The effect of cytostatic drug treatment on intestine-specific transcription factors Cdx2, GATA-4 and HNF-1alpha in mice.
Chemotherapy-induced intestinal damage is a very important dose-limiting side effect for which there is no definitive prophylaxis or treatment. This is in part due to the lack of understanding of its pathophysiology and impact on intestinal differentiation. The objective of this study was to investigate the gene expression of the small intestinal transcription factors HNF-1alpha, Cdx2, GATA-4 in an experimental model of methotrexate (MTX)-induced intestinal damage, and to correlate these alterations with histological damage, epithelial proliferation and differentiation. HNF-1alpha, Cdx2 and GATA-4 are critical transcription factors in epithelial differentiation, and in combination they act as promoting factors of the sucrase-isomaltase (SI) gene, an enterocyte-specific differentiation marker which is distinctly downregulated after MTX treatment. Mice received two doses of MTX i.v. on two consecutive days and were sacrificed 1, 3 and 7 or 9 days after final injection. Segments of the jejunum were taken for morphological, immunohistochemical and quantitative analyses. Intestinal damage was most severe at day 3 and was associated with decreased expression of the transcriptional factors HNF-1alpha, Cdx2 and GATA-4, which correlated well with decreased expression of SI, and seemed inversely correlated with enhanced proliferation of epithelial crypt cells. During severe damage, the epithelium was preferentially concerned with proliferation rather than differentiation, most likely in order to restore the small intestinal barrier function rather than maintaining its absorptive function. Since HNF-1alpha, Cdx2 and GATA-4 are critical for intestine-specific gene expression and therefore crucial in epithelial differentiation, these results may explain, at least in part, why intestinal differentiation is compromised during MTX treatment.


Cancer susceptibility and the functions of BRCA1 and BRCA2.
Inherited mutations in BRCA1 or BRCA2 predispose to breast, ovarian, and other cancers. Their ubiquitously expressed protein products are implicated in processes fundamental to all cells, including DNA repair and recombination, checkpoint control of cell cycle, and transcription. Here, I examine what is known about the biological functions of the BRCA proteins and ask how their disruption can induce susceptibility to specific types of cancer.


Compartmentalized GPCR Signaling from Intracellular Membranes.
G protein-coupled receptors (GPCRs) are integral membrane proteins that transduce a wide array of inputs including light, ions, hormones, and neurotransmitters into intracellular signaling responses which underlie complex processes ranging from vision to learning and memory. Although traditionally thought to signal primarily from the cell surface, GPCRs are increasingly being recognized as capable of signaling from intracellular membrane compartments, including endosomes, the Golgi apparatus, and nuclear membranes. Remarkably, GPCR signaling from these membranes produces functional effects that are distinct from signaling from the plasma membrane, even though often the same G protein effectors and second messengers are activated. In this review, we will discuss the emerging idea of a "spatial bias" in signaling. We will present the evidence for GPCR signaling through G protein effectors from intracellular membranes, and the ways in which this signaling differs from canonical plasma membrane signaling with important implications for physiology and pharmacology. We also highlight the potential mechanisms underlying spatial bias of GPCR signaling, including how intracellular membranes and their associated lipids and proteins affect GPCR activity and signaling.


[Effects of nitric oxide synthases on kidney in early phase of endotoxic shock in macaque].
To study the pathogenesis of kidney injury in early phase of endotoxic shock. Eleven macaques were anesthetized and randomly divided into two groups: an experimental group (n=6), receiving a dose of 2.8 mg/kg lipopolysaccharides (LPS) by intravenous injection, and a control group (n=5), injected with normal saline of 1 ml/kg. The animals were sacrificed 120 minutes following endotoxin injection. With immunohistochemical technique endothelium nitric oxide synthases (eNOS) and inducible nitric oxide synthases (iNOS) protein of the renal tissue were determined. The ultrastructure was studied with electron microscope. Acid phosphatase (ACP) was also assayed. One hundred and twenty minutes after LPS challenge, damages to the glomerulus and renal tubules were found, and lysosomes were increased in the renal cells. iNOS was positively expressed in vascular endothelium of glomerulus and epithelium of renal tubules in the experimental group, but not in the control group. eNOS was positively expressed in vascular endothelium of glomerulus; and peri-vascular region in both groups. The present findings indicate that NO contributed to the pathogenesis of renal injury in the early phase of endotoxic shock in primates.


Two classes of agonist-sensitive Ca2+ stores in platelets, as identified by their differential sensitivity to 2,5-di-(tert-butyl)-1,4-benzohydroquinone and thapsigargin.
In the absence of extracellular Ca2+, extensive Ca2+ release from the platelet intracellular stores [monitored as an increase of intracellular Ca2+ concentration ([Ca2+]i)] is produced by the combined action of the endomembrane Ca(2+)-ATPase inhibitor thapsigargin and 2 nM ionomycin. The titration of Ca2+ unloading with thapsigargin (plus ionomycin) shows that a substantial fraction of the store-associated Ca2+ is released by 8-10 nM thapsigargin, but that 100-200 nM thapsigargin is required for the complete release. The store depletion obtained in similar conditions with a different endomembrane Ca(2+)-ATPase inhibitor, 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBHQ), is always incomplete. It is completed by thrombin or by 10 nM thapsigargin. We conclude that two different types of Ca2+ pumps exist in platelets, one sensitive to TBHQ and to high thapsigargin, the other insensitive to TBHQ and sensitive to low thapsigargin. They are distributed separately in discrete subpopulations of the agonist-sensitive stores. The influx of external Ca2+ is maximal when both types of stores are Ca(2+)-depleted, either by high thapsigargin or by the combined action of low thapsigargin and TBHQ.


Presurgical and Postsurgical MRI Evaluation of Osteochondral Lesions of the Foot and Ankle: A Primer.
The gold standard diagnostic imaging tool for ankle OCLs is magnetic resonance imaging, which allows precise evaluation of the articular cartilage and assessment of the surrounding soft tissue structures. Post-operative morphologic MRI assessment via MOCART scores provide semi-quantitative analysis of the repair tissue, but mixed evidence exists regarding its association with post-operative outcomes. Post-operative biochemical MRIs allow assessment of the collagen network of the articular cartilage via T2-mapping and T2∗ mapping, and assessment of the articular glycosaminoglycan content via delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1rho mapping and sodium imaging.


Hypercalcemia Is of Uncertain Significance in Patients With Advanced Adenocarcinoma of the Prostate.
Hypercalcemia in the setting of prostate cancer is rare with an uncertain pathophysiology and more research is needed into the role of parathyroid hormone-related peptide as a growth factor and possibly target-directed monoclonal antibody therapies.


The myelin-associated glycoprotein inhibitor BENZ induces outgrowth and survival of rat dorsal root ganglion cell cultures.
The novel myelin-associated glycoprotein (MAG) inhibitor BENZ binds to the N-acetylneuraminic acid (Neu5Ac) portion of the N-terminal Ig-like domain of MAG. Treatment of rat dorsal root ganglion (DRG) cell cultures with BENZ-induced outgrowth of neurofilament 200-positive neurites improved survival of neurons and increased the number of GFAP-positive cells, as determined by fluorescence and confocal laser microscopy and by Western immunoblotting. Furthermore, treatment of DRG cell cultures with BENZ repressed gene and protein expression of the small GTPase RhoA but induced expression of Rho GTP-activating proteins 5 and 24, likely to counteract protein kinase A activity. Specifically, expression of inhibitors of neurite outgrowth, for example, Rock2 and PAK4, was repressed, but cofilin 1, a promoter of axonal growth, was induced. We propose that the MAG inhibitor BENZ abrogates the RhoA-ROCK-cofilin pathway to promote neurite outgrowth. Our findings require confirmation by in vivo animal studies.


Neurotoxic effects of trypan blue on rat retinal ganglion cells.
To facilitate the peeling of internal limiting membrane or epiretinal membrane in vitreoretinal surgery, trypan blue (TB) and indocyanine green (ICG) have been used. However, the cytotoxicity of these dyes have been concerned. The aim of this study was to investigate the neurotoxic effects of TB on rat retinal ganglion cells (RGCs) and compare the effect of TB with ICG. Rat RGCs were purified by a two-step immunopanning procedure. In short-time exposure experiments, purified RGCs cultured for 3 days were exposed to 600 mgL(-1) TB, 1500 mgL(-1) TB and 1500 mgL(-1) ICG for 10 sec to 30 min. The number of viable RGCs was counted after 12 hr in culture. In long-time exposure experiments, purified RGCs were cultured for 3 days in TB solutions ranging from 2 to 800 mgL(-1) or in ICG solutions at concentrations from 2 to 250 mgL(-1). Then the number of viable cells was counted. Exposure to 600 mgL(-1) TB, 1500 mgL(-1) TB and 1500 mgL(-1) ICG for short time from 10 sec to 30 min caused a time-dependent damage to RGCs. There was no significant difference in cytotoxicity to RGCs between TB and ICG in short-time exposure. In long-time exposure, TB as well as ICG showed neurotoxic effect on RGCs in a dose-dependent manner. Fifty percentage inhibitory concentration (IC50) of TB to RGCs was calculated as 115 mgL(-1), while that of ICG was 33 mgL(-1). In conclusion, TB induced neurotoxic effect on RGCs in a dose- and time-dependent manner. During the short-time exposure in surgery, there is likely no difference in neurotoxic effect on RGCs between TB and ICG. However, once the dyes are left in the eyes after surgery, TB may show less toxicity on RGCs than ICG.


Identifying inpatient mortality in MarketScan claims data using machine learning.
Inpatient mortality is an important variable in epidemiology studies using claims data. In 2016, MarketScan data began obscuring specific hospital discharge status types for patient privacy, including inpatient deaths, by setting the values to missing. We used a machine learning approach to correctly identify hospitalizations that resulted in inpatient death using data prior to 2016. All hospitalizations from 2011 to 2015 with discharge status of missing, died, or one of the other subsequently obscured values were identified and divided into a training set and two test sets. Predictor variables included age, sex, elapsed time from hospital discharge until last observed claim and until healthcare plan disenrollment, and absence of any discharge diagnoses. Four machine learning methods were used to train statistical models and assess sensitivity and positive predictive value (PPV) for inpatient mortality. Overall 1 307 917 hospitalizations were included. All four machine learning approaches performed well in all datasets. Random forest performed best with 88% PPV and 93% sensitivity for the training set and both test sets. The two factors with the highest relative importance for identifying inpatient mortality were having no observed claims for the patient on days 2-91 following hospital discharge and patient disenrollment from the healthcare plan within 60 days following hospital discharge. We successfully developed machine learning algorithms to identify inpatient mortality. This approach can be applied to obscured data to accurately identify inpatient mortality among hospitalizations with missing discharge status.


A thigmotaxis-based method of recapturing and transporting small mammals in the laboratory.
One of the challenges associated with breeding and testing of wild animals in the laboratory is their drive to escape. Wild rats attempt to escape their cages as soon as they are opened, and recapturing is often difficult and dangerous to laboratory personnel. The authors describe a method of recapturing wild small mammals in a laboratory setting that takes advantage of thigmotaxis, or the natural tendency to move close to walls and other solid objects. They describe a simple device that is easy to construct and can be used to recapture escaped rats and return them to their home cages. The recapture technique is efficient and benefits animals' well-being by minimizing their distress.


Laparoscopic cholecystectomy produces less postoperative restriction of pulmonary function than open cholecystectomy.
This study was undertaken to determine whether laparoscopy produces less postoperative decrease in pulmonary function than does open operation. Ten elective laparoscopic cholecystectomy patients (LC group) were compared to 10 elective open cholecystectomy patients (OC group). Spirometry was performed preoperatively and then postoperatively as soon as each patient was awake and cooperative. The two groups were similar with respect to age, gender, and preexisting medical illness. No patient had underlying cardiopulmonary disease. Postoperatively, forced vital capacity, forced expiratory volume in 1 s, and maximum forced expiratory flow decreased to 56%, 55%, and 43% of preoperative values in the OC group and to 72%, 76%, and 81% of preoperative values in the LC group. These decreases were significantly greater in the OC group as compared to the LC group, P values < or = 0.05. Cholecystectomy had a significant restrictive effect on immediate postoperative pulmonary function. Laparoscopic cholecystectomy produced significantly less restriction.


Understanding science-in-the-making by letting scientific instruments speak: From semiotics to postphenomenology.
Latour encourages us to use science-in-the-making as an entry point to understanding science, because it allows us to see how scientific knowledge is constituted and through which processes the 'absolute certainties' of ready-made science appear. He approaches science-in-the-making from the perspective of semiotics because it enables him (1) to attribute equal importance to humans and nonhumans, and (2) to let the actors in scientific practices speak for themselves. We argue that Latour's semiotic approach to science-in-the-making and his understanding of scientific instruments as inscription devices do not fulfill these desiderata. This, in turn, prevents him from understanding the crucial role that scientific instruments play in science-in-the-making. As an alternative to Latour's semiotic approach, we present a postphenomenological approach to studying science-in-the-making. Using the notion of technological mediation, we argue that scientific instruments actively mediate how reality becomes present to - and is treated by - scientists. Focusing on how intentional relations between scientists and the world are mediated by scientific instruments makes it possible to turn them into genuine actors that speak for themselves, thereby recognizing their constitutive role in the development of the interpretational frameworks of scientists. We then show how a postphenomenological approach can be understood as an ethnomethodology of human-technology relations that meets both of Latour's requirements when studying science-in-the-making.


Nanoparticles do not penetrate human skin--a theoretical perspective.
The penetration of intact particles in the nanometer range (nanoparticles, [NP]) through human skin is a controversial topic, which has attracted much interest from both the pharmaceutical and the personal care industries. Concerns have also been raised about the possible implications that dermal exposure to NP may have for human health, particularly from physical sunblock formulations. Here we use a theoretical approach to determine the feasibility of NP penetration of healthy human skin. The maximum flux of NPs of various dimensions is calculated based on two algorithms that have been developed to model passive diffusion of molecules through skin. The results confirm that NPs are too large to permeate skin by this mechanism. Although components of NPs may dissolve in the skin and measurable amounts have been detected in body fluids, this is not indicative of actual NP transport through the skin. The possible roles for NP formulations in drug permeation enhancement are also considered but are not associated with the penetration of intact NP.


[A pharmacological analysis of pentagastrin-modulated behavior evoked by stimulation of the ventromedial hypothalamus].
The purpose of the present investigations was to examine the neurochemical mechanisms of modulatory effect of pentagastrin (PG) on escape reaction elicited by the threshold electrical stimulation of the ventromedial hypothalamus (VMH) in rabbits. PG administration (35 mcg/kg intraventricularly) was found to transform escape into feeding. This phenomenon was shown to begin at 20 min and to last to 150 min after PG injection. The animals were treated with various antagonists to some classic neurotransmitters of the central nervous system. Kalipsol (0.25, 0.5 mg/kg intravenously) and ketanserin (0.1 mg/kg intravenously) were found to restore feeding into escape. GABA-ergic antagonist baclofen (0.25, 0.5 mg/kg) was demonstrated to shorten to about 30 min the time of feeding after PG administration. Both inderal-beta-adreno-blocker (0.25, 0.5, 1.0 mg/kg) and M-choline antagonist atropine (0.25, 0.5 mg/kg) were found to be ineffective in escape restoration in response to VMH stimulation. The experimental results suggest the important role of N-cholinergic and serotoninergic brain structures in PG transformation of escape elicited from the VMH into feeding.


A swallowed dental prosthesis causing duodenal obstruction in a patient with schizophrenia: Description of a new technique.
Foreign body ingestion has been a fundamental subject in the area of emergency surgery. The problem is encountered across all age groups; however, it is more common in the pediatric age group. Foreign body ingestion is rare in adults and usually occurs accidentally or in those with psychiatric problems, behavioral disorders, emotional disturbance, mental retardation, or impaired judgment caused by alcohol use. A 33-year-old Caucasian man with chronic schizophrenia was admitted to the emergency department with signs of upper gastrointestinal discomfort as a result of ingestion of a lower dental prosthesis. An abdominal X-ray showed the swallowed dental prosthesis in front of the vertebral column. A technique comprising gastrotomy and duodenal kocherization was used to remove the dental prosthesis; the prosthesis could not be removed endoscopically due to its fixed position on the duodenal wall. Surgery of the duodenum is difficult and carries high mortality and morbidity. Therefore, endoscopy should be the first choice for patients in whom a foreign object is demonstrated to be fixed in the duodenum. In cases where endoscopic extraction fails, surgery should be considered. During surgery, foreign bodies should be removed, paying meticulous attention not to harm the integrity of the duodenum. The technique presented in this study was performed successfully without any injury to the duodenum.


Keep it simple: ranking health states yields values similar to cardinal measurement approaches.
To examine the relationship between ordinal and cardinal valuation of health states. We analyzed rank, visual analog scale (VAS), and time trade-off (TTO) responses for 52 health states defined using the EQ-5D classification system developed by the EuroQol Group. We analyzed 179,431 responses from 11,483 subjects in eight countries: Slovenia, Argentina, Denmark, Japan, Netherlands, Spain, United Kingdom, and United States. We first compared responses across methods by frequency of ties and values below dead. Ordinal associations between methods were evaluated using Spearman's correlation and Kendall's tau. Next, we estimated numerical values from rank responses using country-specific conditional logit models. After anchoring predicted values on a common scale, we further investigated the cardinal relationships between rank, VAS, and TTO-based values using Pearson's rho and quadratic regression. For each country, rank responses are less likely than TTO responses to be tied and to indicate that states are worse than dead. In all countries, rank responses show a strong linear correlation with both TTO (Pearson's rho=0.88-0.99) and VAS (rho=0.91-0.98) responses. However, rank-based values imply greater decrements in health for mild states than cardinal values. Illiteracy and innumeracy can hinder implementation of complex preference elicitation techniques in diverse settings and populations. These results indicate that ranking exercises may provide an attractive alternative for health-state valuation.


Modulation of mitochondrial DNA copy number in a model of glioblastoma induces changes to DNA methylation and gene expression of the nuclear genome in tumours.
There are multiple copies of mitochondrial DNA (mtDNA) present in each cell type, and they are strictly regulated in a cell-specific manner by a group of nuclear-encoded mtDNA-specific replication factors. This strict regulation of mtDNA copy number is mediated by cell-specific DNA methylation of these replication factors. Glioblastoma multiforme, HSR-GBM1, cells are hyper-methylated and maintain low mtDNA copy number to support their tumorigenic status. We have previously shown that when HSR-GBM1 cells with 50% of their original mtDNA content were inoculated into mice, tumours grew more aggressively than non-depleted cells. However, when the cells possessed only 3% and 0.2% of their original mtDNA content, tumour formation was less frequent and the initiation of tumorigenesis was significantly delayed. Importantly, the process of tumorigenesis was dependent on mtDNA copy number being restored to pre-depletion levels. By performing whole genome MeDIP-Seq and RNA-Seq on tumours generated from cells possessing 100%, 50%, 0.3% and 0.2% of their original mtDNA content, we determined that restoration of mtDNA copy number caused significant changes to both the nuclear methylome and its transcriptome for each tumour type. The affected genes were specifically associated with gene networks and pathways involving behaviour, nervous system development, cell differentiation and regulation of transcription and cellular processes. The mtDNA-specific replication factors were also modulated. Our results highlight the bidirectional control of the nuclear and mitochondrial genomes through modulation of DNA methylation to control mtDNA copy number, which, in turn, modulates nuclear gene expression during tumorigenesis.


Thin-layer chromatographic method for estimation of gamma-aminobutyric acid from brain.
The present method describes the estimation of gamma-aminobutyric acid (GABA) from adult rat brain by thin layer chromatography (TLC). The major advantage of this TLC method is the sensitivity and repidity of estimation. About 93 to 98 percent recovery is possible by this procedure and this shows linearity up to 9 micrograms. Replicate analysis of GABA by this method shows a co-efficient variation of 1.31%


The prediction of ovulation and monitoring of the fertile period.
Simple and reliable methods have been sought for both predicting and confirming ovulation. Application of these methods could include management of infertile couples to aid in conception and for increasing the reliability of natural family planning (NFP) as a method of birth control. With the advent of specific hormone assays, serial measurements of estrogens, progesterone (and metabolites), and luteinizing hormone have been the gold standard of monitoring ovarian function in women. However, newer and simpler methodologies have been described and are currently either in use or being tested. These include the measurement of basal body temperature (BBT), the evaluation of the volume, consistency and electro-conductivity of cervicovaginal fluid, salivary steroid content and cellular enzymatic activity, the use of enzyme-linked immunosorbent assays applied to solid-phase formats, and the investigation of new hormonal molecules as markers of reproductive state and function. These new technologies are described herein and their potential for monitoring ovarian function is discussed.


Quantifying the evidence for co-benefits between species conservation and climate change mitigation in giant panda habitats.
Conservationists strive for practical, cost-effective management solutions to forest-based species conservation and climate change mitigation. However, this is compromised by insufficient information about the effectiveness of protected areas in increasing carbon storage, and the co-benefits of species and carbon conservation remain poorly understood. Here, we present the first rigorous quantitative assessment of the roles of giant panda nature reserves (NRs) in carbon sequestration, and explore the co-benefits of habitat conservation and climate change mitigation. Results show that more than 90% of the studied panda NRs are effective in increasing carbon storage, with the mean biomass carbon density of the whole NRs exhibiting a 4.2% higher growth rate compared with lands not declared as NRs over the period 1988-2012, while this effectiveness in carbon storage masks important patterns of spatial heterogeneity across the giant panda habitats. Moreover, the significant associations have been identified between biomass carbon density and panda's habitat suitability in ~85% NRs and at the NR level. These findings suggest that the planning for carbon and species conservation co-benefits would enhance the greatest return on limited conservation investments, which is a critical need for the giant panda after its conservation status has been downgraded from "endangered" to "vulnerable".


Scalar-on-function regression for predicting distal outcomes from intensively gathered longitudinal data: Interpretability for applied scientists.
Researchers are sometimes interested in predicting a distal or external outcome (such as smoking cessation at follow-up) from the trajectory of an intensively recorded longitudinal variable (such as urge to smoke). This can be done in a semiparametric way via scalar-on-function regression. However, the resulting fitted coefficient regression function requires special care for correct interpretation, as it represents the joint relationship of time points to the outcome, rather than a marginal or cross-sectional relationship. We provide practical guidelines, based on experience with scientific applications, for helping practitioners interpret their results and illustrate these ideas using data from a smoking cessation study.


Prevalence and severity of carpal tunnel syndrome symptoms among Iranian butchers and their association with occupational risk factors: Implications for ergonomic interventions.
Carpal tunnel syndrome (CTS) is a common disorder among occupations where upper extremities are actively involved in. Many occupational and non-occupational risk factors may contribute to this disorder. Knowledge regarding occupational risk factors can guide us to implement interventional programs. The aim of the present study was to assess the prevalence and severity of CTS symptoms among butchers and their association with several occupational and non-occupational risk factors. In this study, 152 butchers in Hamadan, Iran, were examined. The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) was used to investigate the severity of CTS symptoms among the individuals. Several risk factors such as body mass index (BMI), wrist ratio, active working hours per day, working experience, and the ergonomic quality of hand tools used by butchers were also investigated. Statistical tests such as the crude and robust regression were used to analyze the data. The prevalence of moderate and mild symptoms of CTS were 7% and 54%, respectively. Moreover, 39% of the butchers were free of CTS symptoms. Crude regression analyses showed that the severity of CTS symptoms had a significant relationship with age, work experience, active working hours per day, working hours per week, and ergonomic quality of the hand tools (p value <0.05). There was no significant relationship between the severity of CTS symptoms and wrist ratio and BMI. Results of the robust regression analysis showed a significant relationship between the severity of CTS symptoms with experience, active working hours, and quality of the hand tools. Occupational risk factors such as working experience, active working hours per day, and the ergonomic quality of hand tools are significant risk factors of CTS symptoms among butchers. Slippery handle is the main non-ergonomic feature of knives and cleavers used by butchers. There was no association between BMI and wrist ratio with CTS symptoms.


A sensitive low artifact TMB procedure for the demonstration of WGA-HRP in the CNS.
A TMB reaction with increased sensitivity and lower artifact can be obtained by dividing the Mesulam reaction into two stages. Use of the modified reaction with HRP conjugated wheat germ agglutinin (WGA-HRP) yields a powerful technique for anterograde and retrograde tracing.


Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues.
The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9-15) were evaluated against human lung adenocarcinoma (A549) and human prostate cancer (PC3) cells. This is the first evaluation of the cytotoxicities of these alkaloids in these cancer cell lines and it revealed that analogue 15 had comparable cytotoxic activity to its natural parent compound, (±)-hanishin (3). This study provides useful information for further structural modification of these alkaloids in order to develop novel antitumor agents.


The role of computer games in measuring spirometry in healthy and "asthmatic" preschool children.
To explore the role of respiratory interactive computer games in teaching spirometry to preschool children, and to examine whether the spirometry data achieved are compatible with acceptable criteria for adults and with published data for healthy preschool children, and whether spirometry at this age can assess airway obstruction. Feasibility study. Community kindergartens around Israel and a tertiary pediatric pulmonary clinic. Healthy and asthmatic preschool children (age range, 2.0 to 6.5 years). Multi-target interactive spirometry games including three targets: full inspiration before expiration, instant forced expiration, and long expiration to residual volume. One hundred nine healthy and 157 asthmatic children succeeded in performing adequate spirometry using a multi-target interactive spirometry game. American Thoracic Society (ATS)/European Respiratory Society spirometry criteria for adults for the start of the test, and repeatability were met. Expiration time increased with age (1.3 +/- 0.3 s at 3 years to 1.9 +/- 0.3 s at 6 years [+/- SD], p < 0.05). FVC and flow rates increased with age, while FEV1/FVC decreased. Healthy children had FVC and FEV1 values similar to those of previous preschool studies, but flows were significantly higher (> 1.5 SD for forced expiratory flow at 50% of vital capacity [FEF50] and forced expiratory flow at 75% of vital capacity [FEF75], p < 0.005). The descending part of the flow/volume curve was convex in 2.5- to 3.5-year-old patients, resembling that of infants, while in 5- to 6-year-old patients, there was linear decay. Asthma severity by Global Initiative for Asthma guidelines correlated with longer expiration time (1.7 +/- 0.4 s; p < 0.03) and lower FEF50 (32 to 63%; p < 0.001) compared to healthy children. Bronchodilators improved FEV1 by 10 to 13% and FEF50 by 38 to 56% of baseline. Interactive respiratory games can facilitate spirometry in very young children, yielding results that conform to most of the ATS criteria established for adults and published data for healthy preschool children. Spirometric indexes correlated with degree of asthma severity.


[Standardized methods for detecting arterial hypertension and ischemic heart disease among the workers of industrial enterprises].
Results are reported of a clinico-epidemiological study of 9000 workers with the purpose of evaluation of the incidence of arterial hypertension (AII) and ischemic heart disease (IHD). The incidence of AH was 29% and IHD was 6.5%. This high incidence of these conditions was low according to findings of dispensarization examination of professional collectives, namely, 1-1.5% for AH and 0.8-1% for IHD.


The efficiency of random versus ethno-directed research in the evaluation of Sinai medicinal plants for bioactive compounds.
Hexane, ethyl acetate and ethanol extracts of sixty plant species (growing wild in Sinai, Egypt) were screened for antibacterial and antifungal activities against a range of Gram-positive and Gram-negative bacteria, a yeast and dermatophytic fungi. Plants were collected either by random or ethno-directed methods. Plants collected at random (36 species) were gathered from different districts of Sinai, while the ethnobotanical collection (24 species) comprised species used in the folk medicine of the Bedouins in Sinai. Results indicate that plant sampling based on ethnobotanical approach produced greater number of plants showing antimicrobial activity. The results are discussed with respect to the ethnobotanical correlation of active species.


A view from the center. A former division chief's perspective on being a megadepartmental chairman.
Upon completing his sixth year as chairman of a large department of surgery in a major United States medical school, the author, a neurosurgical chief for 32 years, reflects upon the goals of departmental stewardship. The charges and challenges to any chairman of a multispecialty department are sampled from the perspective of personal experience. The general message could be interpreted as a call to service and a job description.


Contrasting patterns of insulin biosynthesis, compartmental storage, and secretion. Rat tumor versus islet cells.
A series of 3H-leucine pulse-labeling experiments was carried out with dispersed cells freshly isolated from transplanted rat insulinomas. After secreted fractions were separated, insulin was purified and specific activities were determined for both secreted and average cellular insulins. Labeling patterns in this line of tumor cells were compared with those previously established for isolated rat islets. With both tumors and islets, conversion of labeled proinsulin to insulin occurred to the same extent by 2.5 h, suggesting similar onset and half-time of proteolysis in these cells. However, total cellular insulin in tumors attained a threefold higher specific activity than in islets. Because total B-cell mass in these tumors was unknown, either a more rapid proinsulin biosynthesis or diminished cellular storage (or both) could lead to this faster fractional replacement of total stored insulin. Insulin secretion in these tumor cells was insensitive to high glucose but responded, albeit poorly, to leucine plus 3-isobutyl-1-methylxanthine (IBMX). Under all secretory conditions tested, tumor cells continuously secreted insulin at elevated fractional rates, which were slightly higher than fractional insulin secretory rates in maximally glucose-stimulated islets. In contrast with normal islets, newly synthesized insulin was stored homogeneously in tumor cells, and compartmental storage characteristics were not generated by incubation with either 20 mM glucose or leucine plus IBMX in the marking period. Thus, preferential secretion of insulin was never observed in tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Bigger ant colonies reduce herbivory and herbivore residence time on leaves of an ant-plant: Azteca muelleri vs. Coelomera ruficornis on Cecropia pachystachya.
The effect of defence force size in colonies of the ant Azteca muelleri on the time spent to localize, attack and expel the specialized herbivorous beetle Coelomera ruficornis from Cecropia pachystachya bushes was studied in an area of Atlantic forest in northeastern Brazil. Our results show that Azteca muelleri expel Coelomera ruficornis from Cecropia pachystachya and that the number of ants leaving a colony (defence force size) is negatively correlated with the residence time of an adult beetle on the plant. Colonies with larger defence forces recruited larger numbers of ants, resulting in faster herbivore discovery (r 2=0.80; n=17; P<0.001) and reduced herbivore residence time on a leaf (r 2=0.79 n=23; P<0.001) before being driven off by the ants. We also found a negative and significant relationship between herbivore damage on leaves and ant colony size (r 2=0.28; n=17; P<0.05). We conclude that larger colonies have more individuals available to patrol a plant and recruit defenders toward herbivores. This reduces the time spent to locate and expel susceptible herbivores from the plant. Since the plant probably benefits from reduced herbivory and the plant provides food for the ants, the association between Azteca muelleri and Cecropia pachystachya appears mutualistic.


About the organisation of condensed and decondensed non-eukaryotic DNA and the concept of vegetative DNA (a critical review).
Experiments are reviewed that allow one to assign naturally occurring DNA-containing plasmas to either of two classes by virtue of their sensitivity to aggregation upon dehydration in organic solvents. The interphase nuclei of higher cells are relatively insensitive, while the DNA plasmas represented by bacterial nucleoids, vegetative bacteriophage and the chromosomes of dinoflagellates are sensitive. In higher cells the bulk of DNA is organised with histones in the form of nucleosomes. In prokaryotes and in the pool of vegetative phage DNA the most abundant histone-like protein HU is not associated with the bulk DNA, but localised in the border region with ribosomes where transcription and translation occur. These experimental results strongly suggest that the two classes of DNA plasmas are distinguishable by a low (1:10) or high (1:1) protein-to-DNA ratio. The hypothesis is formulated that the vegetative DNA (replicating and transcribing), throughout the living world, is nucleosome-free; during evolution, nucleosomes would have been introduced as a simple and adequate means for compacting the resting DNA. Condensation of DNA does not occur with prokaryotic nucleoids, but does take place when DNA is withdrawn from the vegetative phage pool to become packaged into phage heads. Dinoflagellate chromosomes are rather condensed although structurally different from eukaryotic chromosomes (e.g., those from Euglena) and are much more aggregation-sensitive.


Clinical characteristics and prognosis of non-small cell lung cancer patients with liver metastasis: A population-based study.
The presence of liver metastasis (LM) is an independent prognostic factor for shorter survival in non-small cell lung cancer (NSCLC) patients. The median overall survival of patients with involvement of the liver is less than 5 mo. At present, identifying prognostic factors and constructing survival prediction nomogram for NSCLC patients with LM (NSCLC-LM) are highly desirable. To build a forecasting model to predict the survival time of NSCLC-LM patients. Data on NSCLC-LM patients were collected from the Surveillance, Epidemiology, and End Results database between 2010 and 2018. Joinpoint analysis was used to estimate the incidence trend of NSCLC-LM. Kaplan-Meier curves were constructed to assess survival time. Cox regression was applied to select the independent prognostic predictors of cancer-specific survival (CSS). A nomogram was established and its prognostic performance was evaluated. The age-adjusted incidence of NSCLC-LM increased from 22.7 per 1000000 in 2010 to 25.2 in 2013, and then declined to 22.1 in 2018. According to the multivariable Cox regression analysis of the training set, age, marital status, sex, race, histological type, T stage, metastatic pattern, and whether the patient received chemotherapy or not were identified as independent prognostic factors for CSS (P < 0.05) and were further used to construct a nomogram. The C-indices of the training and validation sets were 0.726 and 0.722, respectively. The results of decision curve analyses (DCAs) and calibration curves showed that the nomogram was well-discriminated and had great clinical utility. We designed a nomogram model and further constructed a novel risk classification system based on easily accessible clinical factors which demonstrated excellent performance to predict the individual CSS of NSCLC-LM patients.


Genome-scale NCRNA homology search using a Hamming distance-based filtration strategy.
NCRNAs (noncoding RNAs) play important roles in many biological processes. Existing genome-scale ncRNA search tools identify ncRNAs in local sequence alignments generated by conventional sequence comparison methods. However, some types of ncRNA lack strong sequence conservation and tend to be missed or mis-aligned by conventional sequence comparison. In this paper, we propose an ncRNA identification framework that is complementary to existing sequence comparison tools. By integrating a filtration step based on Hamming distance and ncRNA alignment programs such as FOLDALIGN or PLAST-ncRNA, the proposed ncRNA search framework can identify ncRNAs that lack strong sequence conservation. In addition, as the ratio of transition and transversion mutation is often used as a discriminative feature for functional ncRNA identification, we incorporate this feature into the filtration step using a coding strategy. We apply Hamming distance seeds to ncRNA search in the intergenic regions of human and mouse genomes and between the Burkholderia cenocepacia J2315 genome and the Ralstonia solanacearum genome. The experimental results demonstrate that a carefully designed Hamming distance seed can achieve better sensitivity in searching for poorly conserved ncRNAs than conventional sequence comparison tools. Hamming distance seeds provide better sensitivity as a filtration strategy for genome-wide ncRNA homology search than the existing seeding strategies used in BLAST-like tools. By combining Hamming distance seeds matching and ncRNA alignment, we are able to find ncRNAs with sequence similarities below 60%.


ABCD2 score has equivalent stroke risk prediction for anterior circulation TIA and posterior circulation TIA.
Transient ischemic attack (TIA) was clinically divided into anterior circulation (AC) or posterior circulation (PC). Previous study reported that ABCD2 score could predict the stroke risk after AC-TIA but might have limitation for PC-TIA. We aimed to classify TIA depending on neuroimaging and assess the value of ABCD2 score for predicting stroke risk in different territories. Research data was from TIA database of the First Affiliated Hospital of Zhengzhou University. TIA patients with acute infarction on diffuse weighted imaging [that is, transient symptoms with infarction (TSI)] were divided into anterior and posterior circulation groups according to the location of infarction. The outcome was recurrent stroke within 7 and 90 days. The predictive power of ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. Overall, 382 AC-TSI and 112 PC-TSI patients were included. There were 38 (9.9%) AC-TSI patients and 11(9.8%) PC-TSI patients who had recurrent stroke at 7 days, and 66 (17.3%) AC-TSI patients and 19 (17.0%) PC-TSI patients who had recurrent stroke within 90 days. At 7 days, the AUC for ABCD2 score was 0.637 (95% confidence interval CI 0.554-0.720) in anterior circulation and 0.683 (95% CI 0.522-0.845) in posterior circulation. The C statistics for ABCD2 score in the two groups were not statistically significant (Z = - 0.499; P = 0.62). Similar result was found when the outcome time-point was set at 90 days. ABCD2 score could predict the short-term risk of recurrent stroke after AC-TSI and PC-TSI, and had similar predictive abilities for AC-TSI and PC-TSI.


Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task.
Dementia of the Alzheimer's type (DAT) is a neurodegenerative disorder marked by loss of hippocampal cholinergic tone and significant memory impairments, specifically for memories acquired prior to disease onset. The nature of this relationship, however, remains debated. The current study used the string pulling task to evaluate the temporal effects of odor discrimination learning in animals with selective cholinergic lesions to determine the role of the septohippocampal cholinergic system in mnemonic function. Rats with 192-IgG-Saporin lesions to the medial septum had a higher number of correct responses in the reversal training when compared to sham rats, suggesting an inability to retrieve the previously learned discrimination; however, no temporal gradient was observed. Furthermore, there were no group differences when learning a novel odor discrimination, demonstrating the ability for all rats to form new memories. These results establish a role for the cholinergic medial septum projections in long-term memory retrieval. The current study provides a behavioral assessment technique to investigate factors that influence mnemonic deficits associated with rodent models of DAT.


18β-Glycyrrhetinic Acid Has Anti-Cancer Effects via Inducing Apoptosis and G2/M Cell Cycle Arrest, and Inhibiting Migration of A549 Lung Cancer Cells.
18β-glycyrrhetinic acid (18β-Gly), which is extracted from licorice root, has various pharmacological properties; however, its anti-cancer effects on lung cancer cells have not been fully established. In this study, we investigated the underlying molecular mechanisms of 18β-Gly. Our results showed that 18β-Gly had significant cytotoxic effects and no apparent side effects. 18β-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18β-Gly, intracellular reactive oxygen species (ROS) levels were significantly increased, and G2/M cell cycle arrest and inhibition of cell migration were induced via the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa (NF-κB) signaling pathways. After pretreatment with the ROS scavenger N-acetyl-L-cysteine or MAPK inhibitors, the expression levels of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase, inhibitor of nuclear factor kappa B, cleaved caspase-3 (cle-cas-3), cleaved poly (ADP ribose) polymerase (cle-PARP), p-p53, p27, p21, and E-cadherin were decreased; and levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, NF-κB, Bcl-2, cyclin B1, cyclase-dependent kinase 1/2 (CDK1/2), N-cadherin, vimentin, and snail homolog 1 (SNAI 1) were increased. In addition, the percentage of cells in the G2/M phase was decreased, and inhibition of migration was reduced. In summary, 18β-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-κB signaling pathways in A549 lung cancer cells. Therefore, 18β-Gly is a novel promising candidate for the treatment of lung cancer.


The effect of carbon dioxide on cerebral arteries.
The constancy of cerebral blood flow and volume relies heavily upon the cerebral arteries' intrinsic ability to respond to changes in the partial pressure of arterial CO2. The physiologic mechanisms underlying these responses have not been determined, although changes in extracellular and intracellular pH, mediation by prostanoids and neural activity have been suggested. CO2 reactivity can be influenced by oxygen status and blood pressure and can vary according to age and brain region. In certain pathological conditions or diseases, it can be severely altered. Modern techniques, which measure CBF in cases of cerebral hemodynamic insufficiency, head injury or tumor, rely on the inherent ability of the cerebral circulation to respond to changing levels of CO2.


Antenatal corticosteroid treatment and placental pathology, with a focus on villous maturation.
Mothers at risk of preterm birth are treated with antenatal corticosteroids, which have advantageous effects for prematurely born infants. Accelerated villous maturation in the placenta is also associated with improved perinatal outcome. The primary aim of this study was to examine the association between antenatal corticosteroids and accelerated villous maturation. The secondary aim was to study associations with other placental pathologies. A retrospective cohort study including 105 women who had (n = 75) or had not (n = 30) been treated with antenatal corticosteroids. The women gave birth between 22+0 and 26+6 weeks of gestation in Stockholm County between 1 April 2004 and 31 March 2007. A pathologist blinded to all clinical data except gestational age examined the placental slides to identify pathology parameters. The outcomes were correlated with antenatal corticosteroid treatment, and confounding factors were adjusted using logistic regression. Accelerated villous maturation was significantly higher in the group treated with corticosteroids (odds ratio 16, 95% CI 2.4-690, p = 0.0005). After adjustment for gestational age and preeclampsia, the difference remained significant (odds ratio 8.9, 95% CI 1.2-389, p = 0.021). No significant associations were found regarding the secondary outcome variables, after adjusting for possible confounders. Antenatal corticosteroid treatment before preterm birth is associated with accelerated villous maturation. This could be one of the pathways by which corticosteroids are beneficial for preterm infants.


Small, Local Governments and Their Management of Hydraulic Fracturing.
Small, local governments are often considered "low capacity" when it comes to environmental management. This article examines how local government officials in 26 municipalities in Pennsylvania have managed high-volume hydraulic fracturing (HVHF or "fracking"). The data show that the perception of the "problems" related to HVHF and perceived resident expectations for if and how local governments should respond to these problems vary by municipality with clear differences between municipalities with zoning and those without zoning. With the exception of one municipality with the unique circumstance of having both active natural gas and coal extraction occurring, all municipalities believed they had adequate capacity to manage the problems associated with HVHF. This result shows the importance of local responses to local problems and calls into question whether capacity-building efforts are necessary in low capacity municipalities.


Primary care for children and adolescents with Down syndrome.
This article reviews the general health care guidelines pertaining to pediatric patients with Down syndrome and presents, in a systems-based approach, an update of the current evidence behind these guidelines. To ensure the best possible long-term outcome for these patients, clinicians should provide routine well-child examinations and immunizations while maintaining a high index of suspicion for comorbid conditions more common in Down syndrome. The primary care provider should be prepared to provide information on community resources, to coordinate care with subspecialists, and to refer to early intervention services as soon as the diagnosis is made.


Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus.
Long non-coding RNAs (lncRNAs) have been implicated in the regulation of gene expression at various levels. However, to date, the expression profile of lncRNAs in status epilepticus (SE) was unclear. In our study, the expression profile of lncRNAs was investigated by high-throughput sequencing based on a lithium/pilocarpine-induced SE model in immature rats. Furthermore, weighted correlation network analysis (WGCNA), gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to construct co-expression networks and establish functions of the identified hub lncRNAs in SE. The functional role of a hub lncRNA (NONRATT010788.2) in SE was investigated in an in vitro model. Our results indicated that 7082 lncRNAs (3522 up-regulated and 3560 down-regulated), which are involved in cell proliferation, inflammatory responses, angiogenesis and autophagy, were dysregulated in the hippocampus of immature rats with SE. Additionally, WGCNA identified 667 up-regulated hub lncRNAs in turquoise module that were involved in apoptosis, inflammatory responses and angiogenesis via regulation of HIF-1, p53 and chemokine signalling pathways and via inflammatory mediator regulation of TRP channels. Knockdown of an identified hub lncRNA (NONRATT010788.2) inhibited neuronal apoptosis in vitro. Taken together, our study is the first to demonstrate the expression profile and potential function of lncRNAs in the hippocampus of immature rats with SE. The defined hub lncRNAs may participate in the pathogenesis of SE via lncRNA-miRNA-mRNA network.


Receptor binding and biological effect of insulin in human adipocytes.
The binding of 125I-labelled insulin to human adipocytes was studied at 37 degrees C. The precipitability of the 125I-labelled insulin preparation (0.03 nmol/l) in trichloroacetic acid and the concentration of biologically active insulin (7.5 nmol/l) remained constant in buffer incubated with human adipocytes (100 microliter cells/ml suspension) for 30--60 minutes at 37 degrees C, whereas more than half of the insulin was inactivated by rat fat cells under the same conditions. A constant level of binding of 125I-labelled insulin (0.03 nmol/l) to human adipocytes was obtained after 45 minutes. The apparent dissociation constant of receptor binding was about 0.2 nmol/l as compared to about 2 nmol/l for rat adipocytes. Conversion of [UP14C]glucose to lipids was stimulated half-maximally by about 0.05 nmol/l of insulin (similar to rat adipocytes). Thus, half-maximal stimulation of human adipocytes was obtained with a recptor occupancy of about 20--30 per cent.


[Determination of lactoferrin in the diagnosis of diseases of the pancreas].
In 29 patients with chronic pancreatitis, 15 patients with malignant tumours of the pancreas and in 30 controls lactoferrin in fluid aspirated from the duodenum was assessed during the cholecystokinin-secretin (CCK-S) test. As compared with the control group, its concentration is significantly higher in patients with chronic pancreatitis, but not in patients with malignant tumours of the pancreas. It is probable that estimation of lactoferrin in the CCK-S test may prove helpful in the differential diagnosis of pancreatic disease.


Phyto-Fabrication of Silver Nanoparticles Using Typha azerbaijanensis Aerial Part and Root Extracts.
Silver nanoparticles (AgNPs) were phyto-synthesized using Typha azerbaijanensis aerial part and root extracts, and their biological activities were investigated. This study was conducted in the Science and Research Branch, Islamic Azad University, Tehran, Iran in 2019. In this experimental study, silver nanoparticles (AgNPs) were phyto-synthesized and the physicochemical properties of AgNPs were determined using UV-Vis (UV-Vis) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Antibacterial and anticancer activity of synthesized AgNPs was determined using microdilution assay, and MTT 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) methods, respectively. The apoptotic effects of AgNPs were investigated using Real-Time PCR and flow cytometry techniques. Morphological analysis of the synthesized AgNPs confirmed the spherical shape of AgNPs with an average size of 10.67 to 16.69 nm. The FTIR spectrum confirmed the presence of phytochemicals from T. azerbayenensis extract at the AgNP surface. Antibacterial experiments showed that phyto-fabricated AgNPs had significant antibacterial activity against Gram-negative bacteria. The AgNPs were significantly cytotoxic against breast cancer cell line (MCF-7) through induction of apoptosis. The phyto-synthesized AgNPs had biological activities could be useful in pharmaceutical applications.


Identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells.
Fucosylation is one of the most important oligosaccharide modifications and is involved in cancer and inflammation. Recently, fucosylated haptoglobin was identified as a possible tumor marker for pancreatic cancer. The molecular mechanism underlying increases in fucosylated haptoglobin in sera of patients with pancreatic cancer seems to be complicated. Our previous study [N. Okuyama, Y. Ide, M. Nakano, T. Nakagawa, K. Yamanaka, K. Moriwaki, K. Murata, H. Ohigashi, S. Yokoyama, H. Eguchi, O. Ishikawa, T. Ito, M. Kato, A. Kasahara, S. Kawano, J. Gu, N. Taniguchi, E. Miyoshi, Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation, Int. J. Cancer 118 (11) (2006) 2803-2808] demonstrated that pancreatic cancer cells secrete a factor, which induces the production of haptoglobin in hepatoma cells. In the present study, we found that interleukin 6 (IL6) expressed in pancreatic cancer is a factor that induces the haptoglobin production, using a neutralizing antibody for IL6. Real-time PCR analyses revealed the up-regulation of fucosylation regulatory genes after IL6 treatment, resulting increases in fucosylated haptoglobin being revealed by a lectin ELISA. This pathway could be one of the possible mechanisms underlying increases in haptoglobin in sera of patients with pancreatic cancer.


Implications of taxonomic misidentification for future invasion predictions: Evidence from one of the most harmful invasive marine algae.
Invasive species have been a focus of concern in recent decades, becoming more problematic due to the cumulative impacts of climate change. Understanding the interactions among stress factors is essential to anticipate ecosystems' responses. Hereby, robust modeling frameworks must be able to identify the environmental drivers of invasion and forecast the current and future of their potential distribution. These studies are essential for the management of invasions and to be prepared for the future we are facing. Here we demonstrate that taxonomic misidentifications may lead to absolutely erroneous predictions, by using as an example one of the worst invasive species in the Mediterranean Sea (Lophocladia lallemandii), which has been misidentified for three decades and now is correctly identified. Consequently, and bearing in mind overall trends in species misidentification due to the loss of taxonomic expertise and the presence of cryptic species, among others, attempts to understand and predict species involved in invasion processes must always first consider taxonomic studies.


CT-based handling and analysis of preclinical multimodality imaging data of bone metastases.
The pathogenesis of bone metastases is a complex and multifaceted process. Often multiple imaging modalities are needed to follow both the structural and functional changes over time during metastatic bone disease. Researchers face extended data sets of one experiment acquired with multiple modalities at multiple points in time. This review gives an overview of an integrated approach for handling these kinds of complex data. It focuses on the analysis of whole-body micro-computerized tomography and optical data handling. We show how researchers can generate side-by-side visualizations of scans taken with one imaging modality at multiple time points and with multiple modalities at one point. Moreover, we highlight methods for normalized volumes of interest selection and quantification of bone volume and thickness.


Solubility switch of gold nanoparticles through hydrogen bond association.
Gold nanoparticles (AuNPs) coated with hexafluoroisopropanol moieties were prepared, and their surface was changed through simple hydrogen bond association with various amines, which allow orientation of the solubility of these AuNPs in determined organic solvents.


Case management: entry-level practice for occupational therapists?
As American businesses have sought means to control employee health benefits, managed care has evolved. This evolution has brought greater demand for case management. Case management is not a profession but a practice area within one's own profession. Case managers come from a variety of disciplines and work in a variety of practice settings, which include medical, psychosocial, educational, vocational, and rehabilitation.


Deletion of arginine codon 229 in the Rhce gene alters e and f but not c antigen expression.
Rh CcEe antigens occur as ce, Ce, cE, or CE alleles in the RBC membrane. Their epitope structures and the location of their cis interacting products remain to be defined. A rare blood sample from a white male whose parents are first cousins was identified. Hemagglutination was performed using standard methods. RH structure and genotype was assessed by Southern blots. Rh transcripts were obtained by gene-specific RT-PCR and sequenced. The mutation was verified by genomic PCR assays. The donor's RBCs typed D+C-c+E-e-f(Rh6)- with a normal c dose, suggesting the Dc- phenotype. Further tests revealed a weak and qualitatively altered e expression. Southern blots indicated a genotype of Dce/dce without other gross changes. RT-PCR detected a triplet deletion (Delta685AGA687) in the Rhce gene that specifies codon 229 for arginine (Arg229). Sequencing of the region around the mutated exon 5 confirmed the donor to be homozygous for the AGA deletion. Arg229 is invariant on external loop 4 and close to the Ala226Pro change specific for e/E polymorphism. The qualitative and quantitative alteration of e antigen defines Arg229 as a crucial component for e/E epitope presentation. Given a normal dose of c antigen, the disruption of f (Rh6) by Arg229 deletion suggests that external loop 4 is a major structural element contributing to the expression of RHCE cis interacting antigenic products.


Spatial characteristics of atrial fibrillation electrocardiograms.
The present study investigates spatial properties of atrial fibrillation (AF) by analyzing vectorcardiogram loops synthesized from 12-lead electrocardiograms (ECGs). After atrial signal extraction, spatial properties are characterized through analysis of successive, fixed-length signal segments and expressed in loop orientation, that is, azimuth and elevation, as well as in loop morphology, that is, planarity and planar geometry. It is hypothesized that more organized AF, expressed by a lower AF frequency, is associated with decreased variability in loop morphology. Atrial fibrillation frequency is determined using spectral analysis. Twenty-six patients with chronic AF were analyzed using 60-second ECG recordings. Loop orientation was similar when determined from either entire 60- or 1-second segments. For 1-second segments, the correlation between AF frequency and the parameters planarity and planar geometry were 0.608 (P < .001) and 0.543 (P < .005), respectively. Quantification of AF organization based on AF frequency and spatial characteristics from the ECG is possible. The results suggested a relatively weak coupling between loop morphology and AF frequency when determined from the surface ECG.


Negative laparotomy rates and outcomes following blunt traumatic injury in the United States.
Exploratory laparotomy remains the mainstay of treatment following blunt abdominal trauma. However, the decision to operate can be difficult in hemodynamically stable patients with unreliable physical exams or equivocal imaging findings. The risk of a negative laparotomy and the subsequent complications must be weighed against the potential morbidity and mortality of a missed abdominal injury. Our study aims to evaluate trends and the effect of negative laparotomies on morbidity and mortality in adults with blunt traumatic injuries in the United States. We reviewed the National Trauma Data Bank (2007-2019) for adults with blunt traumatic injuries who underwent an exploratory laparotomy. Positive or negative laparotomy of abdominal injury was compared. We performed bivariate analysis and a modified Poisson regression to estimate the effect of negative laparotomy on mortality. A sub-analysis of patients who underwent computed tomography (CT) of the abdomen and pelvis was performed. 92,800 patients met the inclusion criteria of the primary analysis. Negative laparotomy rates were 12.0% in this population, down-trending throughout the study. Negative laparotomy patients had a significantly higher crude mortality (31.1% vs. 20.5%, p < 0.001), despite lower injury severity scores (20 (10-29) vs. 25 (16-35), p < 0.001) than positive laparotomy patients. Patients that underwent negative laparotomy had a 33% higher risk for mortality (RR1.33, 95% CI 1.28-1.37, P < 0.001) than positive laparotomy patients after adjusting for pertinent covariates. Patients that underwent CT abdomen/pelvis imaging (n = 45,654) had a lower rate of negative laparotomy (11.1%) and decreased difference in crude mortality (22.6% vs. 14.1%, p < 0.001) compared to positive laparotomy patients. However, the relative risk for mortality remained high at 37% (RR 1.37, 95% CI 1.29 - 1.46, p < 0.001) for this sub-cohort. Negative laparotomy rates in adults with blunt traumatic injuries are trending down in the United States but remains substantial and may show improvement with increased use of diagnostic imaging. Negative laparotomy has a relative risk for mortality of 33% despite lower injury severity. Thus, surgical exploration in this population should be thoughtfully undertaken with appropriate evaluation via physical exam and diagnostic imaging to prevent unnecessary morbidity and mortality.


Different patterns of clonal evolution among different sarcoma subtypes followed for up to 25 years.
To compare clonal evolution in tumors arising through different mechanisms, we selected three types of sarcoma-amplicon-driven well-differentiated liposarcoma (WDLS), gene fusion-driven myxoid liposarcoma (MLS), and sarcomas with complex genomes (CXS)-and assessed the dynamics of chromosome and nucleotide level mutations by cytogenetics, SNP array analysis and whole-exome sequencing. Here we show that the extensive single-cell variation in WDLS has minor impact on clonal key amplicons in chromosome 12. In addition, only a few of the single nucleotide variants in WDLS were present in more than one lesion, suggesting that such mutations are of little significance in tumor development. MLS displays few mutations other than the FUS-DDIT3 fusion, and the primary tumor is genetically sometimes much more complex than its relapses, whereas CXS in general shows a gradual increase of both nucleotide- and chromosome-level mutations, similar to what has been described in carcinomas.


Fast electron transfer processes in cytochrome C and related metalloproteins.
Various free radicals formed on pulse radiolysis of aqueous solutions have been used to investigate the mechanisms of reduction of cytochrome(III) c by inter- and intramolecular electron transfer. The rapid formation of free radicals (t less than 1 mus) and their high reactivity with cytochrome (k approximately 10(8)(-5) x 10(10)M(-1)s(-1)) make such studies feasible. Reduction of cytochrome by free radicls is monitored by optical methods. Fast optical changes in the 1(-500)-mus region correspond to reduction of the iron center; whereas the slower changes in the 10(-500)-ms region are attributed to postreduction conformational changes. It has been concluded that the reduction path is mediated through the crevice and that no reduction intermediates are being formed.


Metabolic engineering of Halomonas campaniensis strain XH26 to remove competing pathways to enhance ectoine production.
Ectoine has gained considerable attention as a high-value chemical with significant application potential and market demand. This study aimed to increase ectoine yields by blocking the metabolic shunt pathway of L-aspartate-4-semialdehyde, the precursor substrate in ectoine synthesis. The homoserine dehydrogenase encoded by hom in H. campaniensis strain XH26 is responsible for the metabolic shunt of L-aspartate-4-semialdehyde to glycine. CRISPR/Cas9 technology was used to seamlessly knockout hom, blocking the metabolic shunt pathway to increase ectoine yields. The ectoine yield of XH26/Δhom was 351.13 mg (g CDW)-1 after 48 h of incubation in 500 mL shake flasks using optimal medium with 1.5 mol L-1 NaCl, which was significantly higher than the 239.18 mg (g CDW)-1 of the wild-type strain. Additionally, the absence of the ectoine metabolic shunt pathway affects betaine synthesis, and thus the betaine yields of XH26/Δhom was 19.98 mg (g CDW)-1, considerably lower than the 69.58 mg (g CDW)-1 of the wild-type strain. Batch fermentation parameters were optimized, and the wild-type strain and XH26/Δhom were fermented in 3 L fermenters, resulting in a high ectoine yield of 587.09 mg (g CDW)-1 for the defective strain, which was significantly greater than the ectoine yield of 385.03 mg (g CDW)-1 of the wild-type strain. This study showed that blocking the metabolic shunt of synthetic substrates effectively increases ectoine production, and a reduction in the competitively compatible solute betaine appears to promote increased ectoine synthesis.


Continuous wound infusion of ropivacaine for the control of pain after thoracolumbar spinal surgery: a randomized clinical trial.
A prospective randomized clinical trial was carried out to observe the analgesic efficacy of ropivacaine for postoperative pain following thoracolumbar spinal surgery. Seventy-one patients with elective posterior thoracolumbar spinal surgery were randomly divided into two groups. Local group received 0.33 % ropivacaine by pump through the wound, and intravenous group received flurbiprofen axetil, pentazocine and palonosetron via intravenous pump. We evaluated the level of pain, the incidence of adverse reactions at 2, 4, 6, 12, 24, 36 and 48 h after operation, and the occurrence of chronic pain 3 months later. There were no significant differences in the pain level between the two groups. However, the incidence of nausea, vomiting and chronic pain was significantly lower in the local group. Our results showed that local infusion of ropivacaine achieved similar analgesic effects to intravenous delivery of analgesic drugs, but significantly reduced incidence of nausea, vomiting and chronic pain.


Vitamin and mineral supplement users. Do they have healthy or unhealthy dietary behaviours?
It is unknown whether people use vitamin and mineral supplements (VMS) to compensate for unhealthy diets, or people whom already have a healthy diet use VMS. Therefore, this study aimed to examine correlates of VMS use and whether VMS users can be categorised into specific clusters based on dietary lifestyle variables. The data used came from the Swiss Food Panel questionnaire for 2010. The sample consisted of 6189 respondents, mean age was 54 years and 47.6% were males. Data was analysed with logistic regression analysis and hierarchical cluster analysis. The results revealed that for VMS use, gender, age, education, chronic illness, health consciousness, benefits of fortification, convenience food and sugar-sweetened beverage consumption were of importance. Cluster analysis revealed three clusters (1) healthy diet, (2) unhealthy diet and (3) modest diet. Compared to non-users a higher percentage of VMS users was categorised in the healthy cluster and a lower percentage in the unhealthy cluster. More VMS-users were categorised as having an unhealthy diet (31.4%) than having a healthy diet (20.6%). The results suggest that both hypotheses-VMS are used by people with unhealthy diets and by people who least need them-hold true meaning.


[Studies on chemical constituents in herbs of Acanthus ilicifolius].
To study the chemical constituents of Acanthus ilicifolius. Chromatographic methods were used to isolate compounds from A. ilicifolius, and chemical and spectral methods were used to elucidate the structures of the isolated compounds. Five compounds, luteolin 7-O-beta-D-glucuronide (1), apigenin-7-O-beta-D-glucuronide (2), methylapigenin-7-O-beta-D-glucuronate (3), uridine (4) and uracil (5) were obtained. 1, 4 and 5 were obtained from the genus for the first time.


Lipofectamine RNAiMAX: an efficient siRNA transfection reagent in human embryonic stem cells.
RNA interference methodology suppresses specific gene expression, thus mimicking loss-of-function mutation and enabling in vitro and in vivo gene function analysis. Lipofectamine RNAiMAX, a new transfection reagent, has been confirmed high efficiency in delivering small interfering RNA (siRNA) into mesenchymal stem cells and neural stem cells. In this study, we used three transfection reagents (Lipofectamine RNAiMAX, Oligofectamine and Lipofectamine 2000) to deliver siRNA into human embryonic stem (hES) cells and compared the silencing efficiency of enhanced green fluorescent protein transgene and Oct4, a key regulator of pluripotency. As a result, siRNA can be delivered into hES cells more efficiently by Lipofectamine RNAiMAX compared with the other two transfection reagents and high efficient knockdown of target genes was obtained by Lipofectamine RNAiMAX even at a low concentration of siRNA. Quantitative real-time PCR showed approximately 90% knockdown of Oct4 transcript with cognate Oct4 siRNA transfection by Lipofectamine RNAiMAX compared to control siRNA. These results demonstrated that Lipofectamine RNAiMAX is an efficient and excellent transfection reagent for delivering siRNA into hES cells.


Changing nonmainstream American English use and early reading achievement from kindergarten to first grade.
This study had 2 principal aims: (a) to examine whether children who spoke Nonmainstream American English (NMAE) frequently in school at the end of kindergarten increased their production of Mainstream American English (MAE) forms by the end of first grade, and (b) to examine concurrent and predictive relations between children's NMAE use and reading skills. A longitudinal design was implemented with 49 children who varied in their spoken NMAE production in kindergarten. Word reading, phonological awareness, and receptive vocabulary skills were measured at both time points. Analyses indicated that most children significantly increased their production of MAE forms between the 2 time points; however, this change was not associated with change in letter-word reading and phonological awareness skills. Regression analyses showed that NMAE use in kindergarten contributed significantly and independently to the variance in word reading in first grade, even after accounting for phonological awareness (although word reading in kindergarten was the best predictor of word reading in first grade). The findings extend previous reports of a significant relation between NMAE use and reading among young children. Theoretical, research, and educational implications of the findings are discussed.


Sonography of gallstones and biliary dilatation without a visible aetiology: the infrequency of obstructing choledocholithiasis.
This paper describes 50 consecutive patients who sonographically had gallbladder stones and dilated bile ducts, but no visible aetiology for the dilatation. We reviewed these cases to determine the frequency of choledocholithiasis in this setting. Common duct stones caused obstruction in only 36% of these patients. Other aetiologies included strictures due to chronic pancreatitis or prior stone passage in 24% of the patients, and malignant obstruction in 16%. In 24% of the patients, no cause was found for biliary dilatation; common duct stones or obstructing tumours were excluded in the group. Since aetiologies other than stones are likely in a majority of cases, further preoperative workup (CT, percutaneous transhepatic cholangiography, ERCP) or intraoperative cholangiography (if the patient requires urgent cholecystectomy) is indicated. The additional studies should provide a diagnosis, help determine whether or not the common duct should be explored, or avoid unnecessary operation in case of incurable malignancy.


Numerical analysis of lime stabilized capping under embankments based on expansive subgrades.
This paper investigates the efficacy of an alternative construction methodology proposed by the authors in the form of a 'C'-shaped lime stabilized capping. It is used for confining expansive clay subgrade soil under embankments carrying flexible pavement at their top, to enhance their performance. The role of capping in controlling moisture ingress responsible for swelling is assessed by studying vertical displacements and suctions in expansive subgrade soils. The load-displacement behavior and the variations in suctions of expansive subgrade soil are studied by using Mohr-Coulomb material model and Van Genuchten Hydraulic Model respectively in FEM based Software PLAXIS 3D. It is observed from the results that; the swelling displacements are considerably reduced and suctions under embankment toe are observed to increase. It can therefore be concluded that, the lime stabilized capping consisting of horizontal buffer layer and vertical cut-offs is effective in controlling swelling displacements in expansive subgrades.


Phototransformation of monovinyl and divinyl protochlorophyllide by NADPH:protochlorophyllide oxidoreductase of barley expressed in Escherichia coli.
The chlorophyll precursors monovinyl protochlorophyllide (MV-PChlide) and divinyl protochlorophyllide (DV-PChlide) were extracted from mutant C-2A' of the unicellular green alga Scenedesmus obliquus which accumulates both protochlorophyllide derivatives in the dark. The two pigments were characterized by absorption and fluorescence spectroscopy and by plasma desorption mass spectrometry. The molecular masses of MV-PChlide and DV-PChlide were determined as 612 and 610 atomic mass units (amu) respectively. Both MV-PChlide and DV-PChlide were accepted as substrates and photoconverted to chlorophyllides in vitro by NADPH:protochlorophyllide oxidoreductase of barley expressed in Escherichia coli.


Diagnosis of aberrations from crystalline samples in scanning transmission electron microscopy.
The Ronchigrams, or shadow images, observed from a thin crystalline sample in a scanning transmission electron microscope characteristically present many sets of fringes, which appear thanks to the coherent interference between the various Bragg-diffracted discs as they overlap in the diffraction plane. A particular region of such patterns can be shown to be independent of the defocus at which they are recorded. The intensity along this so-called achromatic ring depends on the microscope aberrations and can be used to diagnose the wave aberration coefficients, a crucial first step in the operation of an aberration-corrected microscope. A new algorithm is presented that allows the accurate determination of all non-cylindrically symmetric aberrations up to fourth-order from a crystalline sample using this property of the Ronchigram. An experimental procedure for determining the position of and intensity along the achromatic lines, as well as examples of diagnosis from two different crystalline structures, are detailed.


Using umbilical cord blood for the initial blood tests of VLBW neonates results in higher hemoglobin and fewer RBC transfusions.
We previously described a method for reducing early phlebotomy losses from very low birth weight (VLBW) neonates by obtaining the initial blood tests from otherwise discarded fetal blood from the placenta. In the present study we sought to; (1) measure the feasibility of performing this method in actual practice, (2) test the hypothesis that this method would result in higher hemoglobin concentrations and lower erythrocyte transfusion rates in the first week after birth. We conducted two studies in three Intermountain Healthcare NICUs. The first was a feasibility analysis involving 96 VLBW neonates, measuring the success of obtaining the NICU admission laboratory blood tests this way. The second study used case-control methodology to test the hypothesis that this method would result in a higher blood hemoglobin 12 to 24 h after birth, and a lower proportion receiving an erythrocyte transfusion in the first week. In 91 of 96 VLBW neonates (95%) the initial blood tests were successfully obtained with this method. The success rate was not diminished by delayed cord clamping or cord milking, as it was successful in 35 of 36 (97%) such instances. Cases and controls were well matched on demographic and level of illness comparisons. Among cases the hemoglobin generally increased between birth and 12 to 24 h later, but among controls the hemoglobin generally decreased (P<0.05). In the week following birth fewer cases received vasopressors (P<0.01) and erythrocyte transfusions (P<0.001). We judge that it is feasible to collect the initial blood tests of VLBW neonates using otherwise discarded umbilical cord/placental blood, in that this can be accomplished in about 95% of VLBW deliveries. This method, which can be used in addition to either delayed clamping of the umbilical cord or cord milking, results in higher hemoglobin concentrations, less vasopressor use and fewer transfusions in the first week.


Role of PI3K, ERK1/2, and JAK2 Kinases in the Cardioprotective Effect of Deltorphin II during Cardiac Reperfusion.
The signaling mechanism of the cardioprotective effect of deltorphin II was studied in models of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used the selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg), which was administered intravenously 5 min before reperfusion, the PI3K inhibitor wortmannin (0.025 mg/kg), the ERK1/2 blocker PD-098059 (0.5 mg/kg), the inhibitor JAK2 AG490 (3 mg/kg). All kinase blockers were administered 10 min before reperfusion. The infarct-limiting effect of deltorphin II is associated with the activation of PI3K and ERK1/2 and does not depend on JAK2.


Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray.
p63, cytokeratin (CK) 5/6 and CK 14 have been employed in diagnostic pathology as markers of basal, squamous and myoepithelial differentiation in several types of human neoplasms; however, there is scant data on the concurrent expression of these markers in large series of human neoplasms. We analyzed the distribution of these three immunohistochemical markers in 51 normal human tissue samples, 350 carcinomas, 25 malignant melanomas (MMs), and 25 glioblastomas using three serial sections of tissue array research program (TARP)-4 multi-tumor tissue microarray. Also, we performed double immunostainings to characterize the differential distribution of p63/CK 5/6 and p63/CK 14 in normal breast, salivary gland and skin. p63, CK 5/6 and CK 14 were expressed in basal cells of the prostate and respiratory epithelia and in breast and bronchial myoepithelial cells. p63 was also expressed in cytotrophoblast cells of human placenta and in scattered cells of lymph node germinal center. CK 5/6 and CK 14 also stained the cytoplasm of basal cells of esophageal stratified squamous epithelium and transitional epithelial cells of the bladder. No mesenchymal, neural, endothelial, smooth muscle or adipose cells were stained by any of the markers. p63, CK 5/6, and CK 14 were respectively expressed in 92.6%, 75.0%, and 52.9% of the squamous cell carcinomas of the lung, 10.2%, 20.0%, and 7.4% of the ductal carcinomas of the breast, 12.9%, 34.4%, and 11.8% of the serous and 25.0%, 0%, and 0% of the endometrioid carcinomas of the ovary. Lung, prostate and colonic adenocarcinomas, as well as MMs and glioblastomas were only rarely decorated by one of the markers. Only matched samples of 16 squamous cell carcinomas and two ductal carcinomas of the breast co-expressed these three markers. In double immunostainings, p63-CK 5/6, as well as p63-CK 14 were co-expressed by basal/myoepithelial cells of the salivary glands and basal cells of the epidermis. Our results demonstrate that p63, CK 5/6 and CK 14 may be used together in immunohistochemical panels to characterize squamous differentiation in poorly differentiated carcinomas or carcinomas of unknown origin.


Posture-related changes in sympathetic baroreflex sensitivity during normal pregnancy.
Normal pregnancy is associated with vast adjustments in cardiovascular autonomic control. Sympathetic baroreflex sensitivity has been reported to be attenuated during pregnancy in animal models, but most studies in humans are cross-sectional and findings from longitudinal case studies are inconclusive. It remains unclear how sympathetic baroreflex sensitivity is altered longitudinally during pregnancy within an individual in different body postures. Therefore, this study examined the impact of posture on sympathetic baroreflex sensitivity in 24 normal-weight normotensive pregnant women. Spontaneous sympathetic baroreflex sensitivity was assessed during early (6-11 weeks) and late (32-36 weeks) pregnancy and 6-10 weeks postpartum in the supine posture and graded head-up tilt (30° and 60°). In addition, data from the postpartum period were compared with (and no different to) 18 age-matched non-pregnant women to confirm that the postpartum period was reflective of a non-pregnant condition (online supplement). When compared with postpartum (-3.8 ± 0.4 bursts/100 heartbeats/mmHg), supine sympathetic baroreflex sensitivity was augmented during early pregnancy (-5.9 ± 0.4 bursts/100 heartbeats/mmHg, P < 0.001). However, sympathetic baroreflex sensitivity at 30° or 60° head-up tilt was not different between any phase of gestation (P > 0.05). When compared to supine, sympathetic baroreflex sensitivity at 60° head-up tilt was significantly blunted during early (Δ2.0 ± 0.7 bursts/100 heartbeats/mmHg, P = 0.024) and late (Δ1.5 ± 0.6 bursts/100 heartbeats/mmHg, P = 0.049) pregnancy but did not change postpartum (Δ0.4 ± 0.6 bursts/100 heartbeats/mmHg, P = 1.0). These data show that time-course changes in sympathetic baroreflex sensitivity are dependent on the posture it is examined in and provides a foundation of normal blood pressure regulation during pregnancy for future studies in women at risk for adverse pregnancy outcomes.


Low maternal serum levels of pregnancy-associated plasma protein-A during the first trimester are associated with subsequent preterm delivery with preterm premature rupture of membranes.
To assess the relationship between the first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels and pregnancies complicated by preterm delivery. The correlation between PAPP-A levels and gestational age at delivery was analyzed by linear regression. The probabilities of low PAPP-A multiples of the median (MoM) levels between preterm delivery and control population were analyzed by logit model. A positive correlation was noted between the first-trimester PAPP-A MoM levels and gestational age at delivery between 34-38 weeks (p < 0.001). Lower PAPP-A MoM level had a significantly higher likelihood of preterm delivery (p < 0.05). When preterm premature rupture of membranes (PPROM) and preterm labor (PTL) were analyzed separately, there was an increasing likelihood of PPROM with decreasing PAPP-A MoM levels (p < 0.05), but not for PTL with intact membranes. Low maternal serum PAPP-A levels during the first trimester may reflect a trophoblast invasion defect in the maternal-fetal interface, resulting in subsequent preterm delivery, particularly in those of PPROM.


Analysis of biofilm and bacterial communities in the towel environment with daily use.
Towels differ remarkably from other textile products in their fibre structure and usage, and microbial behaviours on towels remain underexplored. Thus, we evaluated biofilm formation on towels during use for 6 months in daily life and analysed its relationship with odour, dullness, and laundry habits. The towels exhibited odour and dullness after 2 months of use and biofilm structures were observed over the 6 months, especially in the ground warp part. Polysaccharides, proteins, nucleic acids, and viable counts on the towels increased over time. The microbiota was significantly different from that on human skin and clothing. Several species of Alphaproteobacteria were correlated with dullness intensity and the quantity of biofilm components. Therefore, bacterial species that specifically adapt to the towel fibre environment could form biofilms. Our results demonstrate bacterial diversity in textile products and suggest careful consideration of the textile fibre material, structure, and usage pattern to control bacterial communities.


Uridylylation of Herbaspirillum seropedicae GlnB and GlnK proteins is differentially affected by ATP, ADP and 2-oxoglutarate in vitro.
PII are signal-transducing proteins that integrate metabolic signals and transmit this information to a large number of proteins. In proteobacteria, PII are modified by GlnD (uridylyltransferase/uridylyl-removing enzyme) in response to the nitrogen status. The uridylylation/deuridylylation cycle of PII is also regulated by carbon and energy signals such as ATP, ADP and 2-oxoglutarate (2-OG). These molecules bind to PII proteins and alter their tridimensional structure/conformation and activity. In this work, we determined the effects of ATP, ADP and 2-OG levels on the in vitro uridylylation of Herbaspirillum seropedicae PII proteins, GlnB and GlnK. Both proteins were uridylylated by GlnD in the presence of ATP or ADP, although the uridylylation levels were higher in the presence of ATP and under high 2-OG levels. Under excess of 2-OG, the GlnB uridylylation level was higher in the presence of ATP than with ADP, while GlnK uridylylation was similar with ATP or ADP. Moreover, in the presence of ADP/ATP molar ratios varying from 10/1 to 1/10, GlnB uridylylation level decreased as ADP concentration increased, whereas GlnK uridylylation remained constant. The results suggest that uridylylation of both GlnB and GlnK responds to 2-OG levels, but only GlnB responds effectively to variation on ADP/ATP ratio.


Application of sepsis calculator in newborns with suspected infection.
To compare actual antibiotic use to the stratification based on the sepsis calculator in newborns with suspected early onset sepsis (EOS). To investigate differences in EOS risk and vital signs between newborns that received early (<12 h) versus late antibiotics (≥12 h of life). Newborns born ≥34 weeks gestation in 2014 treated with antibiotics started within 72 h after birth were included. We calculated the risk per 1000 live births and retrospectively assigned each newborn to one of four recommended categories using the sepsis calculator. There were 2094 newborns, 111 (5.3%) received antibiotics and 108 newborns were included. The incidence of culture-proven EOS was 0.096%. In 57 newborns, the advice of the sepsis calculator was not to start antibiotic therapy. Antibiotic treatment was started early in 66 (61%) and late in 42 (39%) newborns. In the "late treatment" group, clinical condition deteriorated, including two newborns with culture-proven EOS. Tachypnea and respiratory distress were significantly more present. Antibiotic use could be reduced by more than 50%. Newborns with initial low sepsis risk score clinically deteriorated beyond 12 h of life. Continuous good clinical observation remains very important. Prospective validation is necessary to evaluate the safety of this approach.


The dependence of the Chou-Fasman parameters on amino acid side chain structure.
The Chou-Fasman conformational parameters, P, for amino acid residues in proteins are shown to be a linear function of intermolecular force and steric parameters. For alpha- helix, coil and turn parameters, steric effects are predominant; whereas for beta-sheet parameters, intramolecular forces are predominant. Turn and coil parameters show little or no difference in their dependence which is different from that of alpha-helix and in some ways almost reciprocal. Factors which increase the probability of finding an amino acid residue in an alpha-helix usually decrease the probability of finding it in coil or turn. Values of P were calculated for several of the less common amino acids.


A comparison of intraoperative ultrasound versus cholangiography in the evaluation of the common bile duct during laparoscopic cholecystectomy.
Indications for intraoperative evaluation of the common bile duct during laparoscopic cholecystectomy are controversial, as is the goal of either anatomic definition or assessing for choledocholithiasis. One hundred twenty-five consecutive patients undergoing laparoscopic cholecystectomy underwent both intraoperative ultrasound and intraoperative cholangiography. Cholangiography required slightly more time to perform; it was more sensitive (92.8% vs 71.4%) but less specific (76.2% vs 100%) for choledocholithiasis than was ultrasound. Ultrasound was somewhat more difficult to perform, and, particularly in the setting of intraabdominal obesity, was often inadequate at providing clear visualization of the intrapancreatic common bile duct. It did not provide the same anatomic definition as an adequate cholangiogram. The overall incidence of choledocholithiasis was 11.2%.


Accuracy of diagnostic laparoscopy for early diagnosis of abdominal complications after cardiac surgery.
In the early postoperative period after major cardiac surgery using extracorporal circulation, abdominal complications can have serious consequences with a mortality rate of up to 70%. Early diagnosis and the timely institution of therapy are the most important factors to improve the outcome; however, clinical evaluation of the abdomen is difficult in these patients. Diagnostic laparoscopy is a minimally invasive procedure with low procedure-associated morbidity, even in critically ill patients. The aims of our study were to investigate the safety of laparoscopy in critically ill patients suspected to have intraabdominal pathology following cardiac surgery and to evaluate the accuracy of diagnostic laparoscopy compared to laparotomy in this setting. A total of 17 patients were included (13 male, four female, age 52-80 years) in the early (3-30 days) postoperative period after cardiac surgery using extracorporal circulation (10 ACVB, four valve replacement, one aorto-coronary-venous-bypass (ACVB)+ valve replacement, two cardiac transplantation). Clinical and laboratory findings included distended abdomen (17 of 17), elevated white blood cells (12 of 17), elevated C-reactive protein (CRP) (13 of 17), and elevated lactate levels (11 of 17). The decision to perform laparotomy was taken in all patients on the basis of their clinical condition. Diagnostic laparoscopy was always performed immediately before laparotomy. The laparoscopic findings were then compared to the laparotomy findings. In one patient, laparoscopy showed no abnormal findings, this was confirmed on laparotomy. Five patients were found to have massive distension of the large bowel without ischemia on both laparoscopy and laparotomy. Colonic ischemia of the right hemicolon was found laparoscopically in six patients, which was confirmed in all cases by open resection and histological workup. Three patients suffered from acute cholecystitis, which was correctly diagnosed by laparoscopy in all cases. In one patient, laparoscopy revealed fibrinous peritonitis without other findings. Open exploration failed to identify the cause of the peritonitis in this patient. Laparoscopy showed no pathological findings in one patient, but laparotomy then revealed necrotizing pancreatitis confined to the lesser sac. There was one laparoscopy-associated intraoperative complication (6%) in this series. Diagnostic laparoscopy is a minimally invasive procedure that can be performed at low intraoperative risk in critically ill patients and has a high sensitivity (94%) for the correct diagnosis of intraabdominal complications after major cardiac surgery. These results suggest that bedside laparoscopy should be considered for all patients with equivocal abdominal symptoms in this setting.


Serum IgG and IgD and levels in some infectious and noninfectious diseases.
Serum IgG and IgD levels were determined in the following groups: professional blood donors, healthy smokers and patients with acute hepatitis, with acute salmonellosis, with hepatic cirrhosis, with cancer (prostate, lung and gastrointestinal tract) and with benign diseases of the same organs as the cancer patients. IgG was significantly increased in the groups of patients with hepatitis, hepatic cirrhosis and cancer. IgD values showed a wide dispersion in all the groups, which do not allow for comparisons among means. For that reason, linear regression analysis between IgG and IgD was done, the results being significant only in the two groups with infectious diseases (acute hepatitis and acute salmonellosis), which suggest that IgD could be involved in the immune response against their respective pathogenic agents.