Effect of labetalol or lidocaine on the hemodynamic response to intubation: a controlled randomized double-blind study.
Labetalol, a combined alpha 1- and nonselective beta-adrenergic blocking drug, was compared to lidocaine or saline to minimize the hypertensive and tachycardic response to intubation in a controlled randomized double-blind study in patients undergoing surgical procedures under general anesthesia. Forty adult patients were divided into four groups of 10 each: placebo (saline), lidocaine 100 mg, labetalol 5 mg, or labetalol 10 mg. The double-blind preparation was administered as an IV bolus just prior to induction and 2 min before the stimulus of laryngoscopy and intubation. Heart rate and blood pressure were measured at 1-min intervals for 2 min prior to induction of anesthesia and through 6 min following induction of anesthesia. Labetalol 10 mg prevented a rise in heart rate after intubation compared to patients who received placebo, lidocaine 100 mg, or labetalol 5 mg. The hypertensive response to intubation was similar in all four groups. Labetalol 10 mg IV just prior to induction of anesthesia is a safe and cost-effective means of preventing tachycardia but not hypertension in response to laryngoscopy and intubation.


Experimental models of splenic dysfunction.
Animal simulations of splenic disorders are described including alterations in portal and splenic vein flow, induction of splenic sequestration, models of hyposplenism and murine hereditary spherocytosis.


Krebs von den Lungen 6 decreased in the serum and muscle of GNE myopathy patients.
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is necessary for sialic acid biosynthesis. GNE myopathy is caused by a defect in GNE, and hyposialylation is a key factor in the pathomechanism of GNE myopathy. Although candidates for evaluating hyposialylation have been reported, it is difficult to measure them in routine clinical practice. Sialylation is necessary for synthesis of various glycoproteins, including Krebs von den Lungen-6 (KL-6)/mucin 1 (MUC1). Here we report that KL-6/MUC1 is decreased in GNE myopathy. We observed that KL-6 levels were decreased in the serum of patients with GNE myopathy, and that KL-6 and MUC1-C were also decreased in muscle biopsy specimens from these patients. An immunofluorescent study revealed that KL-6 and MUC1-C were not present in the sarcolemma but were, instead, localized in rimmed vacuoles in specimens from patients with GNE myopathy. KL-6 is already used to detect lung diseases in clinical practice, and this glycoprotein may be a novel candidate for evaluating hyposialylation in GNE myopathy.


[Differential diagnosis of interstitial lung diseases].
It is reported on the different forms of the interstitial pulmonary diseases. Apart from the clinical examination the establishment of the professional and hobby anamnesis play an important part for the differential diagnosis. Allergologic and immunologic examination methods may contribute to the etiologic clarification. In unclear findings a bioptic ascertainment is necessary, though histologically not all cases are to be clarified. The author enters the most important clinical pictures and refers to the difficulties of the radiological differential diagnostics. Questions of therapy are briefly discussed.


An example of nutrient control of gene expression: amino acid-dependent regulation of asparagine synthetase.
Amino acid deprivation of mammalian cells causes a significant enhancement in gene expression for a number of important cellular activities, among these is included asparagine synthetase (AS). A full length cDNA clone for rat AS was isolated previously from a subtracted cDNA library enriched for amino acid-regulated sequences. The present report summarizes the use of the AS cDNA to investigate the amino acid-dependent regulation of AS mRNA in normal rat liver and Fao hepatoma cells. In response to complete amino acid starvation, there was an increase in steady state AS mRNA content. Three species of mRNA, approximately 2.0, 2.5 and 4.0 kb, were detected and each was simultaneously regulated to the same degree. In hepatoma cells the increased AS mRNA content was prevented by either actinomycin D or cycloheximide. Partial repression of the AS mRNA content was maintained by the presence of a single amino acid in the culture medium, but the effectiveness varied. Glutamine effectively repressed the AS mRNA content, even at a concentration 10 times below its plasma level. Conversely, depletion of selected single amino acids from complete culture medium also caused up-regulation. A role for tRNA charging in the signalling mechanism was suggested by the observation that the addition of histidinol, an inhibitor of histidinyl tRNA synthetase, caused an increase in AS mRNA content when added to complete medium. The increased AS mRNA is associated with polysomes and is actively translated. The data indicate that nutrient regulation of the rat AS gene occurs by a general control mechanism that is responsive to the availability of selected individual amino acids.


Correction to: Advancing Pharmacotherapy Development from Preclinical Animal Studies.
In the 7th line from the bottom of the Abstract the word nociception appears incorrect.


Twenty-four hour insulin secretion and beta cell NEFA oxidation in type 2 diabetic, morbidly obese patients before and after bariatric surgery.
We have previously demonstrated that type 2 diabetes resolves after bariatric surgery. To study the role of NEFA in the prompt normalisation of beta cell glucose sensitivity, insulin secretion and beta cell glucose and lipid metabolism were investigated by a model of nutrient-stimulated insulin secretion using a multiple-meal test. Hourly glucose, C-peptide and NEFA were measured in nine morbidly obese, type 2 diabetic patients before and 1 week after bariatric surgery and in six matched healthy volunteers over 24 h. A mathematical model of glucose-NEFA comodulation of insulin secretion rate (ISR) was used to compute ISR and beta-oxidation. Insulin sensitivity was measured by an OGTT minimal model. Beta cell sensitivity to glucose and NEFA was doubled after surgery, while the 24 h insulin secretion decreased from 277.1 +/- 144.4 to 198.0 +/- 107.6 nmol/m(2) (p < 0.02). Insulin sensitivity was restored. The beta-oxidation rate of beta cells was completely normalised (from 0.032 +/- 0.012 x 10(-12) to 0.103 +/- 0.031 x 10(-12) mmol/min per cell, p < 0.005). The best predictor of beta cell function improvement was the duration of diabetes. Bariatric surgery in type 2 diabetes restores beta-oxidation in beta cells, doubles glucose-NEFA sensitivity and reverses diabetes. It is likely that ISR is reduced to match insulin-sensitivity normalisation, in spite of no significant reduction in NEFA levels. We hypothesise that insulin sensitivity normalisation might appear as a consequence of nutrient exclusion from proximal intestinal transit, and that secondarily the need for insulin secretion diminishes. The insulin sensitivity increase is much higher than usually obtained by insulin-sensitising agents and is independent of weight changes.


Cerebral implants and Parkinson's disease: a unique form of biographical disruption?
Chronic illness is perceived as a particular kind of event. The aim of this paper is to understand the personal, familial and professional difficulties experienced by patients in France who have a neurodegenerative disease and undergo cerebral implants. This paper is based on the assumption that a treatment using biotechnical techniques is a unique disruptive experience which redefines the patient's life. Thirty patients (13 women and 17 men) from two French hospitals were interviewed at different stages of their medical history. Despite the excellent overall outcome of neurosurgery in patients with Parkinson's disease, there is often a contrast between the improvement in motor disability and the patient's difficulty in returning to normal life. These results allow us to analyse the link between the neurosciences and the experience of chronic illness.


[Effect of ciprofloxacin on the phagocytosis of Escherichia coli by human polymorphonuclear leukocytes].
Brief exposure of bacteria to high concentrations of some antimicrobials enhanced their susceptibility to phagocytic killing by human polymorphonuclear leucocytes. This effect was defined as Post Antibiotic Leukocyte Enhancement or PALE. In this study we have investigated the effect of prior exposure of E. coli for ten minutes to 0.99 mg/l of ciprofloxacin and 0.40 mg/l of meropenem. The pretreated bacteria were incubated for three hours in a mixture containing leukocytes and leukocytes plus serum (10% v/v). Leukocytes were prepared from blood of healthful volunteers and were extracting with ammonium chloride and differential centrifugation. At one hour intervals, aliquots were taken and added to basic water to dispute leukocytes and spread onto agar plates. Viable bacteria were counted. PALE of ciprofloxacin was higher than meropenem. Whether PALE is confirmed, it must be taken into consideration in dosage schedules.


Endovascular treatment for life-threatening hemoptysis due to rupture of descending thoracic aortic aneurysm: A case series.
Aortic aneurysm is an uncommon but life-threatening cause of hemoptysis. Treatments include surgery and/or endovascular intervention, each with its own advantages and disadvantages. Endovascular intervention is associated with good early and medium-term outcomes. We report three cases of hemoptysis due to ruptured thoracic aortic aneurysm who underwent endovascular intervention. In all three cases, endovascular grafts were placed in the descending thoracic aorta, the number of grafts used was 1, the average time to stop hemoptysis was 4 to 5 days, and the length of hospital stay was between 6 and 8 days. No intravascular fistula, renal failure, prolonged mechanical ventilation and other major cardiovascular events were reported. Endovascular treatment for descending TAA has been demonstrated to be safe and effective, particularly in emergencies in which patients presented with life-threatening hemoptysis, due to its rapid access to the aorta. In our experience at a tertiary hospital in southern Vietnam, the procedural time for a thoracic endovascular aortic repair is relatively brief and can last between 15 and 30 min. Thus, endovascular treatment for ruptured TAA can substantially improve patient prognosis, reduce mortality and complications. The implementation of endovascular intervention can help improve prognosis, reduce mortality and complications in patients with hemoptysis due to ruptured thoracic aortic aneurysm.


Functional outcomes after chemoradiotherapy of laryngeal and pharyngeal cancers.
Organ preservation regimens that combine chemotherapy and radiotherapy (chemoradiotherapy) are increasingly used as the primary treatment of laryngeal and pharyngeal cancers. Meta-analytic data show a survival benefit with combined modality therapy, but the functional sequelae can be significant. Dysphagia is recognized as a common and often devastating late effect of chemoradiotherapy. This review examines functional outcomes after chemoradiotherapy for laryngeal and pharyngeal cancers, with a particular emphasis on dysphagia. Topics examined include the burden of dysphagia after chemoradiation, pathophysiology of dysphagia, baseline functioning, recommendations to improve long-term function, and voice outcomes.


Association of single nucleotide polymorphisms in CAPN1, CAST and MB genes with meat color of Brahman and crossbreed cattle.
The objective of this research was to determine the association of SNPs in the candidate genes Calpain (CAPN1), Calpastatin (CAST) and Myoglobin (MB) with colorimetric parameters (L *, a *, b *, C *, hue) in a F1 population (n = 164) obtained from crossing Bos taurus × Bos indicus and Bos indicus × Bos indicus. SNPs were analyzed using PCR-RFLP and SSCP. Colorimetric measurements were performed in the muscles Longissimus thoracis et lumborum (LTL) and Semitendinosus (ST) at 7, 14 and 21 days postmortem applying the methodology CIE L* a* b*. The CAST gene showed a significant effect on the b* and hue* parameters in both muscles. MB gene showed significant association with all colorimetric parameters in both LTL and ST muscles, except with b* parameter. The CAPN1 gene did not show any significant association. These results suggest an important role of genetics in meat color variation for cattle raised under the tropic conditions.


Creation of endoglucanase-secreting Streptomyces lividans for enzyme production using cellulose as the carbon source.
We screened for high-activity endoglucanase (EG) as a first step toward the creation of cellulose-assimilating Streptomyces lividans transformants. EGs derived from Thermobifida fusca YX, Tfu0901, and S. lividans, cellulase B (CelB), were successfully expressed. Genes encoding Tfu0901 or CelB were introduced into S. lividans using the integrative vector pTYM18 and the high-copy-number vector pUC702, and EG activity was detected in the supernatant of each transformant. To achieve coexpression of EG and transglutaminase, the transglutaminase gene was introduced into EG-secreting S. lividans using pUC702. S. lividans coexpressing EG and transglutaminase effectively assimilated phosphoric acid swollen cellulose. The yield of Streptomyces cinnamoneus transglutaminase in the culture supernatant was 7.2 mg/L, which was 18 times higher than that of the control strain. To demonstrate the versatility of our system, we also created an EG-producing S. lividans transformant capable of coexpressing endoxylanase. The EG-secreting S. lividans transformants constructed here can be used to produce other useful compounds through cellulose fermentation.


Effect of zinc source (zinc sulfate or zinc hydroxychloride) on relative abundance of fecal Treponema spp. in lactating dairy cows.
Previous research revealed a potential effect of dietary trace mineral source on both ruminal and fecal microbiota. However, the effect of Zn source, specifically, has not previously been considered. Based on reported postruminal solubility, we hypothesized that Zn hydroxychloride would decrease Treponema spp. fecal excretion relative to cows fed Zn sulfate. To test this hypothesis, lactating Holstein cows (n = 24; 685 ± 9 kg of body weight; 159 ± 8 d in milk; parity 3 ± 0.2) were randomly assigned to 1 of 2 dietary treatments: control (75 mg/kg Zn from ZnSO4) or Zn hydroxychloride (HYD; 75 mg/kg IntelliBond Z; Micronutrients USA LLC). Single fecal grab samples were collected on d 1 before dietary treatments and on d 27 after dietary treatments were applied. Fecal microbial DNA was extracted and sequenced to establish taxonomy using a universal primer for the 16S rRNA gene. Supplementation of HYD decreased the relative abundance of Treponema 2 by 3-fold (14.7% vs. 4.9%). Poor sequencing resolution at the species level limited inference of Treponema spp. toward management or gut health implications of HYD supplementation. However, the inclusion of pathogenic species among Treponema spp. indicates a potential implication of HYD feeding to reduce environmental exposure of the dairy cow to Treponema spp.


Enhanced proliferation of progenitor cells in the subventricular zone and limited neuronal production in the striatum and neocortex of adult macaque monkeys after global cerebral ischemia.
Cerebral ischemia in adult rodent models increases the proliferation of endogenous neural progenitor cells residing in the subventricular zone along the anterior horn of the lateral ventricle (SVZ a) and induces neurogenesis in the postischemic striatum and cortex. Whether the adult primate brain preserves a similar ability in response to an ischemic insult is uncertain. We used the DNA synthesis indicator bromodeoxyuridine (BrdU) to label newly generated cells in adult macaque monkeys and show here that the proliferation of cells with a progenitor phenotype (double positive for BrdU and the markers Musashi 1, Nestin, and beta III-tubulin) in SVZ a increased during the second week after a 20-min transient global brain ischemia. Subsequent progenitor migration seemed restricted to the rostral migratory stream toward the olfactory bulb and ischemia increased the proportion of adult-generated cells retaining their location in SVZ a with a progenitor phenotype. Despite the lack of evidence for progenitor cell migration toward the postischemic striatum or prefrontal neocortex, a small but sustained proportion of BrdU-labeled cells expressed features of postmitotic neurons (positive for the protein Neu N and the transcription factors Tbr 1 and Islet 1) in these two regions for at least 79 days after ischemia. Taken together, our data suggest an enhanced neurogenic response in the adult primate telencephalon after a cerebral ischemic insult.


Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury.
The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a non‑proteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead‑, cadmium‑, and exercise‑induced oxidative stress. Astrocytes and neuron cells were co‑cultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factor‑α, interleukin‑6, caspase‑3, p53, B‑cell lymphoma 2 and Bcl‑2‑associated X protein were determined. These inflammatory, apoptotic, and oxidative stress markers were substantially increased in injured cells, and returned to normal levels following taurine supplementation. Thus, taurine supplementation may be effective against oxidative stress, apoptosis, and inflammation in injured brain cells.


Origin and morphology of nerve fibers in the aganglionic colon of the lethal spotted (ls/ls) mutant mouse.
The lethal spotted mutant mouse (ls/ls) develops congenital megacolon because of the absence of ganglia in the terminal colon. This aganglionosis results from a failure of neural crest cells to colonize this area during fetal life. We have postulated that the microenvironment of the aganglionic segment of bowel is abnormal. Our hypothesis suggests that this abnormal enteric microenvironment fosters the sprouting of neuritic processes. We further propose that neural and glial precursors cease to migrate once they have extended their definitive processes. As a result, the area distal to the site where neurite extension is favored does not become colonized by neural or glial precursors. A prediction of this hypothesis is that the aganglionic tissue should be innervated by axons from neurons located both in the more proximal ganglionated bowel and in ganglia located outside the gut. Neurons and their processes in control and ls/ls terminal gut were located by the histochemical demonstration of acetylcholinesterase (AChE) activity and their structure was classified as intrinsic (enteric) or extrinsic in type by electron microscopy. In ls/ls mice the submucosal plexus was much more severely affected than the myenteric plexus. No submucosal ganglia were found within 30 mm of the anus. In contrast, myenteric ganglia extended to within 4 mm of the anus on the mesenteric side of the gut and to within 15 mm on the antimesenteric side. Rostral to the areas that were absolutely aganglionic, both plexuses were hypoganglionic, especially the submucosal plexus, which was hypoganglionic throughout the entire colon. Both the aganglionic and caudal hypoganglionic zones of the ls/ls bowel were penetrated by large nerve trunks that had the ultrastructural characteristics of extra-enteric peripheral nerve. Unusual ganglia, outside the enteric musculature in the adventitia of the colon, were connected to these trunks. The location of the cell bodies of origin of the nerve fibers in the terminal colon of control mice and in the aganglionic segment of the bowel in ls/ls mice was determined by following the retrograde transport of tracers injected as close as possible to the anus. An extrinsic innervation originating from the inferior mesenteric ganglion and dorsal root ganglia (L6-S1) was found in both types of animal. In control but not ls/ls mice retrograde labeling was also observed in the sacral parasympathetic nucleus of the spinal cord. In addition, neuritic processes were traced to neurons in myenteric ganglia. In control mice, these labeled neurons were present in ganglia within the injection site as well as in bowel rostral and caudal to it.(ABSTRACT TRUNCATED AT 400 WORDS)


Normalization schemes for ultrafast x-ray diffraction using a table-top laser-driven plasma source.
We present an experimental setup of a laser-driven x-ray plasma source for femtosecond x-ray diffraction. Different normalization schemes accounting for x-ray source intensity fluctuations are discussed in detail. We apply these schemes to measure the temporal evolution of Bragg peak intensities of perovskite superlattices after ultrafast laser excitation.


Evidence against the 1:2:2:1 quartet DMPO spectrum as the radical adduct of the lipid alkoxyl radical.
It was reported that the electron paramagnetic resonance (EPR) spectrum of 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/lipid alkoxyl radical exhibited a quartet with 1:2:2:1 relative intensity that is identical to that of DMPO/hydroxyl radical (K. M. Schaich and D. C. Borg, 1990, Free Radicals Res. Commun. 9, 267-278). We repeated these EPR experiments using HPLC separation of radical adducts and isotope substitution. We found that the HPLC/EPR chromatogram of the radical adduct with a 1:2:2:1 quartet obtained by the reduction of methyl linoleate hydroperoxide (MLOOH) with Fe2+ exhibited identical retention time to that of the DMPO/OH radical adduct obtained from the Fenton reaction in two different solvent systems. Upon performing the same reaction in 17O-enriched water, the 17O-hyperfine coupling constants due to DMPO/17OH were identified. Ultimately, approximately 80-90% of the total DMPO/OH is derived from water by an iron-dependent nucleophilic addition reaction. Initially, a water-independent mechanism also significantly contributes to DMPO/OH formation. Regardless of its mechanism of formation, the 1:2:2:1 quartet radical adduct of DMPO formed during the reduction of MLOOH by Fe2+ is in fact DMPO/OH.


Relationships between adverse childhood experiences and adult mental well-being: results from an English national household survey.
Individuals' childhood experiences can strongly influence their future health and well-being. Adverse childhood experiences (ACEs) such as abuse and dysfunctional home environments show strong cumulative relationships with physical and mental illness yet less is known about their effects on mental well-being in the general population. A nationally representative household survey of English adults (n = 3,885) measuring current mental well-being (Short Edinburgh-Warwick Mental Well-being Scale SWEMWBS) and life satisfaction and retrospective exposure to nine ACEs. Almost half of participants (46.4 %) had suffered at least one ACE and 8.3 % had suffered four or more. Adjusted odds ratios (AORs) for low life satisfaction and low mental well-being increased with the number of ACEs. AORs for low ratings of all individual SWEMWBS components also increased with ACE count, particularly never or rarely feeling close to others. Of individual ACEs, growing up in a household affected by mental illness and suffering sexual abuse had the most relationships with markers of mental well-being. Childhood adversity has a strong cumulative relationship with adult mental well-being. Comprehensive mental health strategies should incorporate interventions to prevent ACEs and moderate their impacts from the very earliest stages of life.


Noradrenaline depletion protects cholinergic neurons in rat hippocampus against AF64A-induced damage.
The role of the noradrenergic system in the cholinotoxicity of ethylcholine aziridinium ion (AF64A) was studied in rats. Male Sprague-Dawley rats were treated with the noradrenergic neurotoxin DSP-4 (N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine; 50 mg/kg i.p.) in the presence of the serotonin uptake inhibitor fluoxetine, 14 days prior to bilateral intracerebroventricular injection of AF64A (2 nmol/lateral ventricle). In rats in which noradrenaline (NA) was depleted by 94%, the loss of acetylcholine (ACh) in hippocampus induced by AF64A was significantly attenuated (p less than 0.02). However, when there was only a partial depletion of NA (50% reduction), the AF64A-induced loss of ACh was a pronounced as in rats with intact noradrenergic function. These findings indicate that the noradrenergic lesion has to be complete before a protective effect is apparent. Moreover, they imply that noradrenergic input is involved in AF64A-induced cholinergic damage in the hippocampus.


Molecular characteristics of H9N2 influenza viruses isolated from farmed raccoon dogs and arctic foxes in China.
In this study, eight H9N2 IAVs were isolated from infected diseased, farmed raccoon dogs and arctic foxes. Eight genes shared 98.6%-100% identity among the isolates possessing a PSRSSR/GL motif at the HA cleavage site, which is same as the motif of G1 and Y280 lineages of H9N2 IAVs. The phylogenetic analysis showed that the HA genes of the eight isolates clustered with Y280-like viruses, whereas the NA genes belonged to F/98-like sublineage. Interestingly, the NS, NP, PB2 and PA genes of the isolates were closely related to H7N9 IAVs. This is the first evidence for isolation of H9N2 IAVs from raccoon dogs and arctic foxes. Raccoon dogs and arctic foxes potentially serve as an intermediate host for influenza viruses with pandemic potential toward other animals due to co-expression of both SA α-2,6-Gal and SA α-2,3-Gal receptors in a wide range of their tissues.


Area deprivation is associated with poorer overall survival in children with acute lymphoblastic leukemia.
Few studies have evaluated social determinants of outcomes disparities for children with acute lymphoblastic leukemia (ALL). We investigated the association of area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, with overall survival (OS) among children and adolescents with ALL. We obtained demographic and clinical data, geocoded addresses at diagnosis, and vital status on all Texas children diagnosed with ALL from 1995 to 2011 (N = 4104). Using the US Census Bureau 2010 geography, we computed ADI scores for all census tracts in Texas and grouped the tracts into quartiles: least, third-most, second-most, and most disadvantaged. We mapped children to ADI quartiles based on residence at diagnosis, and estimated OS using Cox regression adjusting for sex, race/ethnicity, age, and metropolitan/nonmetropolitan residence. Five-year OS ranged from 89% (95% confidence interval [CI] 87-91%) for children in the least disadvantaged tracts to 79% (95% CI 76-81%) for children in the most disadvantaged tracts (P = 4E-7). An elevated hazard ratio (HR) for death was observed for children in the most disadvantaged tracts (HR 1.57, 95% CI 1.23-2.00), and trends toward increased mortality were observed in the third-most and second-most disadvantaged tracts (HR 1.23, 95% CI 0.97-1.57 and HR 1.27, 95% CI 0.99-1.62, respectively). In stratified analyses, area disadvantage was more strongly associated with OS in males than females. Neighborhood socioeconomic disadvantage is associated with inferior OS in this analysis of over 4100 children with ALL, highlighting the substantial contributions of social-environmental factors to childhood cancer survival. This association was stronger in males than females.


Hepatic fibrosis: new insights into pathogenesis.
From available clinical and experimental data, the deterioration of hepatocellular function associated with fibrosis may be ascribed, in part, to loss of biologic support provided by a normal extracellular matrix. These studies of pathogenesis are expected to clarify new points of therapeutic intervention and also to rationalize empiric therapies.


COMPUTATIONAL ASSESSMENT OF PREGNANT WOMAN MODELS EXPOSED TO UNIFORM ELF-MAGNETIC FIELDS: COMPLIANCE WITH THE EUROPEAN CURRENT EXPOSURE REGULATIONS FOR THE GENERAL PUBLIC AND OCCUPATIONAL EXPOSURES AT 50 Hz.
The Recommendation 1999/529/EU and the Directive 2013/35/EU suggest limits for both general public and occupational exposures to extremely low-frequency magnetic fields, but without special limits for pregnant women. This study aimed to assess the compliance of pregnant women to the current regulations, when exposed to uniform MF at 50 Hz (100 μT for EU Recommendation and 1 and 6 mT for EU Directive). For general public, exposure of pregnant women and fetus always resulted in compliance with EU Recommendation. For occupational exposures, (1) Electric fields in pregnant women were in compliance with the Directive, with exposure variations due to fetal posture of <10 %, (2) electric fields in fetuses are lower than the occupational limits, with exposure variations due to fetal posture of >40 % in head tissues, (3) Electric fields in fetal CNS tissues of head are above the ICNIRP 2010 limits for general public at 1 mT (in 7 and 9 months gestational age) and at 6 mT (in all gestational ages).


Establishment and characterization of the third non-functional human pancreatic neuroendocrine tumor cell line.
The mechanisms of neuroendocrine tumor (NET) were still poorly understood, largely due to the lack of preclinical models of neuroendocrine neoplasms. Herein, we established and characterized SPNE1 cell lines from primary pancreatic NET tissue obtained from a 44-year-old female. Neuroendocrine character of SPNE1 was compared with existing non-functional cell lines BON1 and QGP1, and the results indicated expressions of multiple NET-specific markers in SPNE1 were higher relative to BON1 and QGP1. The growth character measured by Ki67 labeling index, cell cycle analysis, and 3D matrigel spheroid essay indicated that the proliferative rate of SPNE1 was lower than that of BON1 and QGP1. SPNE1 also was characterized with cancer stemness because of the higher proportion of CD44 + and CD117 + subpopulations relative to BON1, whereas it was similar to that of QGP1. Interestingly, SPNE1 highly expressed somatostatin receptors (SSTR2 and SSTR5) and angiogenic factors (VEGF1). SPNE1 had sensitive response to the four clinical treatments including tyrosine kinase inhibitor (TKI), mTOR inhibitors, somatostatin analogs (SSA), chemotherapy, which was similar to the BON1 and QGP1. Subcutaneous transplantations of SPNE1 also present the tumorigenicity, and neuroendocrine marker expression of xenograft tumors resembled the original human NET tissue. Then, we found a total of 8 common mutation in BON1, QGP1 and SPNE1 included CROCC, FAM135A, GPATCH4, CTBP2, FBXL14, HERC2, HYDIN, and PABPC3 using whole-exome sequencing (WES), and more neuroendocrine-related functional processes were enriched based on the private mutation genes in SPNE1, such as neuron migration, insulin secretion, and neuron to neuron synapse. In brief, SPNE1 could be used as a relevant model to study pancreatic NET biology and to develop novel treatment options.


Mature Ovarian Cystic Teratoma Mimicking a Bladder Diverticulum in a 16-year-old Female.
A 16-year-old female was incidentally found to have an abnormal pelvic ultrasound while undergoing evaluation for mild scoliosis. A large, thick-walled, lobular, fluid-filled structure was found at midline in the pelvis that initially resembled bladder diverticula due to its anatomical position and sonographic appearance. Voiding cystourethrogram and computed tomography later revealed a large cystic mass originating from the right ovary. This report outlines a case of a mature cystic teratoma convincingly mimicking bladder anomaly on sonography.


Increased effect of apomorphine on homovanillic acid in rats terminated from chronic haloperidol.
Rats who were administered apomorphine seven days after termination of chronic treatment with haloperidol had significantly (59%) lower level of brain HVA than saline control rats. This finding is consistent with the behavioral evidence suggesting supersensitivity of post-synaptic dopamine receptors after termination of chronic haloperidol.


Liposome associated interferon-alpha-2b functions as an anti-fibrogenic factor in dermal wounds in the guinea pig.
We have previously reported that interferon-alpha-2b (IFN-alpha-2b) can be encapsulated in liposomes without compromising its anti-fibrogenic effects on dermal fibroblasts in vitro. This study was conducted to determine whether this preparation applied topically to guinea pig wounds can affect their healing. The rationale for this approach is that systemic administration of IFN-alpha-2b by injection for treatment of dermal fibrosis is uncomfortable, requires a large quantity of the cytokine and cannot be easily used in children. Liposomes are potentially useful vehicles for the topical delivery of drugs. Empty sonicated liposome vesicles were mixed with various concentrations of IFN-alpha-2b and then dried and rehydrated. An enzyme-linked immunosorbent assay (ELISA) was used to determine the efficiency of encapsulation and the stability of the preparation under experimental conditions. A total of 36 full thickness skin wounds (6/animal, 3 on each side) were made with an 8 mm disposable punch. Each wound on the right side received cream (100 mg/wound) containing 3000 units of liposome-encapsulated IFN-alpha-2b, while wounds on the left side received cream containing empty liposomes. There was a significant reduction in rate of contraction of wounds treated with IFN-alpha-2b as early as 5 days after wounding. This reduction remained significant up to 10 days. Northern analysis, used to evaluate the expression of mRNAs for type I and type III collagens in response to IFN-alpha-2b showed a marked reduction in abundance of the transcripts for the pro-alpha1(I) chain of type 1 collagen on days 11 and 14 after wounding. Similarly, the level of mRNA for type III procollagen was markedly reduced as early as day 7 and remained depressed up to day 14. These findings were consistent with results obtained for the total collagen content in tissue samples. Cellularity of the IFN-alpha-2b-treated wounds, assessed by vimentin content, was also markedly reduced at day 7 and remained depressed up to day 14. Liposome associated IFN-alpha-2b applied 5 days after completion of epithelialization reduced mRNA for the pro-alpha1(I) chain of type 1 collagen, confirming its transepidermal penetration and effectiveness. The activity of liposome-associated IFN-alpha-2b in vivo supports the concept of the topical use of this anti-fibrogenic agent for treatment of fibroproliferative disorders.


The impact of inocula carryover and inoculum dilution on the methane yields in batch methane potential tests.
Batch studies are used to benchmark biohydrogen potential (BHP) and biomethane potential (BMP) yields from feed substrates, digestates residues and different process configurations. This study shows that BMP yields using cellulose can be biased positively by not diluting the initial sewage sludge inoculum and the bias is independent of starting inoculum volatile solids (VS) concentration. The carryover of BHP inoculum also increased the BMP yields when using cellulose as a substrate by up to 18.8%. Furthermore it was also observed that the dilution of BMP inoculum with deionised H2O reduced methane yields from cellulose by up to 132±26 N mL-CH4 g-VS(-1). Therefore it is proposed that inoculum and standard substrate controls (as used in this study) should be included in methane batch methodologies, particularly when using a pre-fermentation stage such as dark fermentation.


Japanese Braille Translation Using Deep Learning - Conversion from Phonetic Characters (Kana) to Homonymic Characters (Kanji).
A blind student writes and submits reports in Braille word processor, which is difficult for teachers to read. This study's purpose is to make a translator from Braille into mixed Kana-Kanji sentences for such teachers. Because Kanji has homonyms, it is not always possible to get correct results when converting. To overcome this difficulty, we used deep learning for translation. We built a training dataset composed from 15,000 pairs of Braille codes and mixed Kana-Kanji sentences, and a validation dataset. In training, we got an accuracy of 0.906 and a good Bleu score of 0.600. In validation, we found 5 mistaken words in selecting homonymous Kanji by examining translation mistakes from 100 pairs of the verification sentences. The choice of homonymous Kanji depends on the context. For decreasing such type of errors, it is necessary to introduce of translation of paragraphs by increasing the scale of the network model in deep learning, and to expand the network structure.


Metal ion accessibility of histidine-modified superfolder green fluorescent protein expressed in Escherichia coli.
Green fluorescent protein (GFP) is frequently utilized for metal ion detection and quantification. To improve the metal binding potential of GFP, three residues (N146, F165, and L201) were substituted to histidines. Each variant responded differently upon interaction with metal ions. More than 80% of N146H, having the most accessible surface area, could bind to immobilized metal ions. However, only F165H exhibited significant differences in quenching by soluble metal ions (22% fluorescence decrease) in comparison with the template protein (12%). These findings can be utilized for designing GFP variants for metal binding and sensor applications.


Thoracic vertebral actinomycosis: Actinomyces israelii and Fusobacterium nucleatum.
Actinomyces spp. are considered rare pathogens in today's medicine, especially with thoracic vertebral involvement. Classic actinomycosis (50%) presents as an oral-cervicofacial ("lumpy jaw") infection. This report describes a case of spinal cord compression caused by Actinomyces israelii with the coisolation of Fusobacterium nucleatum. There are limited numbers of similar cases.


Concentrations, profiles, and emission factors of unintentionally produced persistent organic pollutants in fly ash from coking processes.
The coking process has been found to be an important source of unintentionally produced persistent organic pollutants (UP-POPs). However, the concentrations, profiles, and emission factors of UP-POPs in fly ash from coke plants have not been studied. In this study, six UP-POPs (polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), hexachlorobenzene (HxCBz), and pentachlorobenzene (PeCBz)) were identified and quantified in fly ash from eight coke plants. The average concentrations of the PCDDs, PCDFs, and "dioxin-like" PCBs were 1.5, 2.26, and 0.26 pg TEQ g(-1), respectively, and the average concentrations of the PCNs, HxCBz, and PeCBz were 256, 290, and 146 pg g(-1), respectively. The proportion each homolog contributed to the total concentration of the PCDFs, PCBs, and PCNs decreased with increasing chlorination level. The PCDFs contributed the biggest proportion of the total UP-POPs toxic equivalents (TEQs), and the average emission factors in fly ash were 10.5, 17.3, and 1.82 ng TEQt(-1) for the PCDDs, PCDFs, and "dioxin-like" PCBs, respectively, and 1,792, 2,028, and 1,025 ngt(-1) for the PCNs, HxCBz, and PeCBz, respectively. These data are essential for establishing an integrated UP-POP release inventory.


Structure and function of the yeast tRNA ligase gene.
We report here the DNA sequence of the entire coding region of the Saccharomyces cerevisiae tRNA ligase gene. tRNA ligase is one of two enzymes required for tRNA splicing in yeast, and the enzyme is likely a single polypeptide with multiple activities. We find that tRNA ligase is a basic protein of 827 amino acids corresponding to a molecular weight of approximately 95,400. The inferred amino acid sequence for tRNA ligase is not significantly homologous to that of other known proteins of similar activity. In addition to the tRNA ligase reading frame and several other unidentified open reading frames, we have found two open reading frames, ORF1 and ORF2, near the 5'-end of the ligase structural gene. One of these, ORF2, produces a divergent transcript which initiates only 125 nucleotides upstream of the tRNA ligase transcript, and is present in approximately the same relative abundance as the transcript for tRNA ligase.


A Systematic Review of Short-Term Outcomes of Leadless Pacemaker Implantation After Transvenous Lead Removal of Infected Cardiac Implantable Electronic Device.
The outcomes of leadless pacemaker (LP) implantation after transvenous lead removal (TLR) of infected cardiac implantable electronic devices (CIEDs) are not well-established. This study sought to describe the outcomes of LP implantation after TLR of infected CIED. We conducted a literature search using PubMed and Embase for a combination of terms including LP implantation, transvenous lead extraction, TLR, transvenous lead explant, infected CIED, infected pacemaker, and infected implantable cardioverter defibrillator. The inclusion criterion was LP implantation after TLR of infected CIED. The exclusion criterion was TLR for noninfectious reasons. Study end points included procedural complications and LP infection during follow-up. Of 132 publications reviewed, 13 studies with a total of 253 patients (74 ± 14 years of age, 174 [69%] males) were included. The most common indication of the initial device implantations was a high-degree atrioventricular block (n = 100 of 253, 39.5%). Of the 253 patients included, 105 patients (41.5%) underwent concomitant LP implantation during the TLR procedure, and 36 patients (14.2%) had temporary transvenous pacing as a bridge from TLR to LP implantation. Of the 148 patients with data on the type of CIED infection, 56.8% had systemic CIED infection and 43.2% had isolated pocket infection. Staphylococcus aureus was the most common causative organism in 33% of the reported patients. The LP was implanted an average of 5.4 ± 10.7 days after TLR of infected CIED. During the LP implantation, 1 patient (0.4%) had unsuccessful implantation because of an intraprocedural complication requiring sternotomy. After LP implantation, 2 patients (0.8%) developed groin hematoma, 2 patients (0.8%) developed femoral arteriovenous fistula, and 1 patient (0.4%) developed pericardial effusion requiring pericardiocentesis. During a mean follow-up of 11.3 ± 10.6 months, 3 patients (1.2%) developed pacemaker syndrome, 1 patient (0.4%) developed acute on chronic heart failure exacerbation, and only 1 patient (0.4%) developed LP-related infection requiring LP retrieval. This study suggests that LP implant is feasible and safe after removal of infected CIED with cumulative adverse events at 4% and a reinfection rate of 0.4%. Large prospective studies are needed to better evaluate the best timing of LP implantation after TLR of an infected CIED.


In vivo characterization of fatty acids in human adipose tissue using natural abundance 1H decoupled 13C MRS at 1.5 T: clinical applications to dietary therapy.
Natural abundance proton-decoupled (13)C magnetic resonance spectroscopy was used to establish the in vivo lipid composition of normal adipose tissue and the corresponding effects of altered lipid diets. Experiments were performed on a standard 1.5 T clinical MR scanner using a double-tuned (1)H-(13)C coil. Peaks from double-bonded and methylene carbons were analyzed. Normal lipid composition was established in 20 control subjects. For comparison, five subjects on altered lipid diets were studied. Four subjects were on a fish oil supplement diet or predominantly seafood diet (polyunsaturated fatty acids), and one subject was on a Lorenzo's oil diet (monounsaturated fatty acids). Well-resolved (13)C spectra were obtained from the calf adipose tissue with a total acquisition time of 10 min. Model oil solutions were used to identify specific (13)C resonances. Subjects on lipid diets showed significantly elevated levels of monounsaturated and polyunsaturated fatty acids for Lorenzo's and fish oil diets, respectively. We conclude that (13)C MR spectroscopy can readily detect changes in lipid composition due to medium- and long-term therapeutic lipid diets. Since the examination is rapid, robust and noninvasive, opportunities arise for large clinical trials of preventive or therapeutic diets to be performed with (13)C MRS on a clinical MR scanner.


No evidence for motor-recovery-related cortical connectivity changes after stroke using resting-state fMRI.
It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state (rs) functional MRI (fMRI). Here, we report a longitudinal data set collected from 19 patients with subcortical stroke and 11 controls. Patients were imaged up to five times over 1 year. We found no evidence, using rs-fMRI, for longitudinal poststroke cortical connectivity changes despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here, we argue instead that they are consistent with other emerging reasons to challenge the idea of motor-recovery-related cortical reorganization poststroke when conceived of as changes in connectivity between cortical areas.NEW & NOTEWORTHY We investigated longitudinal changes in functional connectivity after stroke. Despite substantial motor recovery, we found no differences in functional connectivity patterns between patients and controls, nor any changes over time. Assuming that rs-fMRI is an adequate method to capture connectivity changes between cortical regions after brain injury, these results provide reason to doubt that changes in cortico-cortical connectivity are the relevant mechanism for promoting motor recovery.


Reproduction, growth, and defense trade-offs vary with gender and reproductive allocation in Ilex glabra (Aquifoliaceae).
Male-biased herbivory in dioecious species is expected as a consequence of selection for increased resistance (reduced attack) in the sex with higher reproductive costs-females. Empirical support of this prediction is taxonomically restricted and fraught with exceptions. Phenological changes in resource allocation to reproduction may change the trade-offs among functions in a sex-specific fashion, and may eliminate male-biased herbivory. We investigated variation in trade-offs among reproduction, growth, and defense in relation to the reproductive period, and whether females were more resistant and less tolerant (maintaining fitness upon damage) than males in a natural population of Ilex glabra in Nova Scotia. We subjected plants to partial or full defoliation treatments during and after flowering in 2006 and before flowering in 2007, and measured their growth and reproductive output in 2007. We assessed resistance to herbivory using the proportion of leaf damage found on leaves obtained from the defoliation treatment. Contrary to theoretical predictions, we did not find male-biased herbivory. Males were more tolerant than females to being partially defoliated before or after flowering. Regardless of sex, plants either fully or overcompensated after partial defoliation, and under-compensated in response to full defoliation, except when defoliated before flowering. Rather than a trade-off, we found a weak, positive correlation between resistance and tolerance. The timing of damage in relation to reproductive phenology influences both resistance and tolerance to herbivory, which must be considered when assessing predictions about gender dimorphism of biotic interactions.


Home parenteral nutrition in adults: a multicentre survey in Europe in 1993.
A retrospective survey was performed in 1994, involving 496 adult home parenteral nutrition (HPN) cases, newly enrolled in the year 1993 from 13 European countries from 75 centres. From the 8 countries having registered more than 80% of cases (423 patients), incidence and prevalence ranged from 0.2 to 4.6 and 0.3 to 12.2 patients/10(6) population/year. In the patients studied, the diagnosis was cancer (42%), Crohn's disease (15%), vascular diseases (13%), radiation enteritis (8%), AIDS (4%) and other nonmalignant non-AIDS diseases (18%). Short bowel syndrome and intestinal obstruction were the two major indications for HPN in 31% and 22%, respectively. Seventy-three percent of the centres had a nutrition team. HPN was administered through a tunnelled venous central catheter in 73%, cyclical nocturnal infusions were used in 90% of patients, and intravenous feeding was the sole source of nutrition in 33%. Only 44% undertook HPN unaided. The present report indicates that cancer has now become the main indication for HPN in Europe; there was, however, a heterogeneous distribution of diseases amongst the reporting countries. The observed 9 (6-12)-month probability of survival was poor in AIDS (n = 8; 12%) and cancer patients (n = 78; 29%) but better for the other HPN indications (n = 115; 92%).


Spontaneous osteonecrosis of the knee (SONK).
Spontaneous osteonecrosis of the knee (SONK/Morbus Ahlback) mainly affects the medial condyle of elderly women. It is assumed that localized vascular insufficiency leads to necrosis of the subchondral bone with subsequent disruption of the nutrition supply to the cartilage above. The aetiology remains unclear in detail. Operative treatment procedures compete against non-operative strategies, whereas the outcome is unpredictable in many cases. A consecutive case series of five patients suffering from SONK was analysed. All patients underwent a clinical examination, magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry scan, as well as laboratory analyses and visual analogue scale (VAS) evaluation. Our treatment regime is based on high-dose vitamin D administered orally and intravenous application of 3 mg ibandronate two times within 8 weeks. Another 8 weeks later, all patients were followed up including a follow-up MRI. Within 4 weeks, all patients were free of symptoms. The MRI follow-up showed remission of the bone marrow oedema in every case studied. VAS decreased significantly from 7.4 ± 1.0 pre-interventional to 0.8 ± 1.0 post-interventional. No allergic reactions or other side effects were documented. We showed that our treatment regime not only eliminated the pathological findings in the MRI of all cases studied, but also decreased the pain level and functional limitations within a short-time period. IV.


A Thematic Analysis of Online Discussion Boards for Vasectomy.
To examine posts on Internet discussion groups related to vasectomies, and identify common ideas through a structured theme analysis. Internet discussion boards were identified using the search term "vasectomy." Three discussion boards were identified as having the most posts and were chosen for analysis. Using an iterative and structured analysis process, each post was analyzed using thematic analysis in 3 steps (open coding, axial coding, and selective coding) to determine common themes. A total of 129 posts were analyzed. The most common posts related to changes in sexual function after vasectomy. The second most common theme was pain after vasectomy. There were also posts about considerations before vasectomy, planning for postvasectomy care, what to expect after vasectomy, potential issues after vasectomy and how to manage these, and feelings about vasectomy. Some of the information present did not have a factual basis. Posts dedicated to postvasectomy pain and sexual dysfunction were of the highest quantity. There was no medical provider input to these discussion boards. Educational efforts should be targeted to these areas and should include a health-care professional.


Magnetic resonance cholangiopancreatography versus endoscopic ultrasound for diagnosis of choledocholithiasis: an updated systematic review and meta-analysis.
Both endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are used for the diagnosis of choledocholithiasis (CDL). Previous studies have shown conflicting results regarding the optimal diagnostic strategy for suspected CDL; hence, this meta-analysis was conducted. A comprehensive search of literature from 1990 till April 2022 was done of three databases for studies comparing EUS and MRCP to diagnose CDL. A total of 12 studies were identified. The pooled sensitivity and specificity for EUS were 0.96 [95% confidence interval (CI) 0.92-0.98], and 0.92 (95% CI 0.85-0.96), respectively. The pooled sensitivity and specificity for MRCP were 0.85 (95% CI 0.78-0.90) and 0.90 (95% CI 0.79-0.96), respectively. EUS had a higher relative sensitivity [Relative risk (RR) 1.12, 95% CI 1.05-1.19], a higher diagnostic accuracy (Odds ratio 1.98, 95% CI 1.35-2.90) but comparable specificity (RR 1.02, 95% CI 0.96-1.08) with MRCP. There is little difference concerning specificity, although EUS likely provides a higher sensitivity and accuracy for diagnosing CDL, compared to MRCP.


Optical and rogue type soliton solutions of the (2+1) dimensional nonlinear Heisenberg ferromagnetic spin chains equation.
In this study, the uses of unified method for finding solutions of a nonlinear Schrödinger equation that describes the nonlinear spin dynamics of (2+1) dimensional Heisenberg ferromagnetic spin chains equation. We successfully construct solutions to these equations. For each of the derived solutions, we provide the parametric requirements for the existence of a valid soliton. In order to visualize some of the discovered solutions, we plot the 2D and 3D graphics. The results of this investigation, which have been presented, might be useful in elucidating the model's physical significance. These are a highly useful tool for studying how electrical solitons, which travel as voltage waves in nonlinear dispersive media, spread out, as well as for doing various physical calculations. The study's findings, which have been disclosed, might be useful in illuminating the models under consideration's physical significance and electrical field.


Getting the proto-Pax by the tail.
Pax genes encode transcription factors governing the determination of different cell types and even organs in the development of multicellular animals. Pax proteins are characterized by the presence of three evolutionarily conserved elements: two DNA-binding domains, the paired domain (PD) and paired-type homeodomain (PtHD), and the short octopeptide sequence (OP) located between PD and PtHD. PD is the defining feature of this class of genes, while OP and/or PtHD may be divergent or absent in some members of the family. Phylogenetic analyses of the PD and PtHD sequences do not distinguish which particular type of the extant Pax genes more resembles the ancestral type. Here we present evidence for the existence of a fourth evolutionarily conserved domain in the Pax proteins, the paired-type homeodomain tail (PHT). Our data also imply that the hypothetical proto-Pax protein most probably exhibited a complex structure, PD-OP-PtHD-PHT, which has been retained in the extant proteins Pax3/7 of the ascidia and lancelet, and Pax7 of the vertebrates. Finally, based on structural considerations, a scenario for the evolutionary emergence of the proto-Pax gene is proposed.


Adjuvant SOX chemotherapy versus concurrent chemoradiotherapy after D2 radical resection of locally advanced esophagogastric junction (EGJ) adenocarcinoma: study protocol for a randomized phase III trial (ARTEG).
Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection. In this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL). In the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection. ClinicalTrials.gov NCT03973008 . Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1.


New technical possibilities for simultaneous cystometry.
With the introduction of integrated semiconductor pressure pick-ups into the urodynamic methodology of analysis, the bladder and urethral manometry has been optimized, since the measuring transducer is positioned directly inside the lumen of the bladder. In this way, it is possible to eliminate the errors of conventional measuring methods with the liquid-filled or gas-filled catheter system, for example movements, vibrations, hydrostatic influences on the coupling medium by different vertical positions of the catheter or connecting tube, as well as cloggings due to haematuria or secretion of mucus. Owing to its dimensions and radiopaque properties, the IBW 78 tip manometer is suitable also for the pressure measurement in the upper urinary passages including the pyelon. The pressure signals obtained are further processed in a special plug-in unit for the biomonitor system, and thus they can be recorded on any multiple recorder.


The relationship between cardiac function and metabolism in acute adriamycin-treated perfused rat hearts studied by 31P and 13C NMR spectroscopy.
Acute adriamycin cardiotoxicity was studied in the isolated, perfused rat heart by 31P and 13C NMR spectroscopy at flow rates of 15 and 5 ml/min. Treated hearts received a total dose of 13.5 mg of adriamycin. 31P NMR spectra were collected at the beginning and end of each experiment, and cardiac function was recorded throughout. Hearts were perfused with [1-13C]glucose, and 13C NMR spectra were recorded in the presence and absence of the drug. At normal flow (15 ml/min), adriamycin caused a decline in cardiac function which was reversible when the drug was removed. There were no changes in high energy phosphate levels. The labeling of glutamate was unchanged in the presence of adriamycin; however, there was a slight increase in the labeling of lactate and alanine. At reduced flow (5 ml/min), control hearts exhibited a small decrease in ATP and phosphocreatine levels, and cardiac function was depressed. These changes were reversible when normal flow was restored. Nevertheless, adriamycin treatment at low flow caused an irreversible decline in function and in hydrolysis of ATP and phosphocreatine. At reduced flow, the control and drug-treated hearts showed similar labeling of the glutamate pool; however, there was significantly greater labeling of lactate and alanine during adriamycin treatment. These results indicate that adriamycin is more toxic under reduced flow conditions. Impairment of cardiac function by adriamycin without changes in glutamate labeling suggests that this drug alters the relationship between cardiac function and energy production.


Dirac cones and chiral selection of elastic waves in a soft strip.
We study the propagation of in-plane elastic waves in a soft thin strip, a specific geometrical and mechanical hybrid framework which we expect to exhibit a Dirac-like cone. We separate the low frequencies guided modes (typically 100 Hz for a 1-cm-wide strip) and obtain experimentally the full dispersion diagram. Dirac cones are evidenced together with other remarkable wave phenomena such as negative wave velocity or pseudo-zero group velocity (ZGV). Our measurements are convincingly supported by a model (and numerical simulation) for both Neumann and Dirichlet boundary conditions. Finally, we perform one-way chiral selection by carefully setting the source position and polarization. Therefore, we show that soft materials support atypical wave-based phenomena, which is all of the more interesting as they make most of the biological tissues.


Inhibition of farnesyltransferase reduces angiogenesis by interrupting endothelial cell migration.
Inhibitors of farnesyltransferase (FTI) have been developed for cancer treatment for more than a decade. Aside from being a therapeutic target in tumor cells, little is known about the role of farnesyltransferase (FTase) in other physiological processes. In this study, we revealed the involvement of FTase in angiogenesis and showed that FTI inhibited angiogenesis by directly acting on endothelial cells. Inhibition of FTase interrupted cell migration in vitro and in vivo. In addition, we found that FTase was important for cell polarization, cell spreading and pseudopodia formation. We also found that FTase interacted with microtubule end binding protein 1 (EB1) and that this interaction was critical for the localization of EB1 to microtubule tips. Our findings thus offer novel insight into the functions of FTase in endothelial cells and provide valuable information for the use of FTI in cancer therapy.


Uniquely insidious: Yersinia pestis biofilms.
Bubonic plague, one of history's deadliest infections, is transmitted by fleas infected with Yersinia pestis. The bacteria can starve fleas by blocking their digestive tracts, which stimulates the insects to bite repeatedly and thereby infect new hosts. Direct examination of infected fleas, aided by in vitro studies and experiments with the nematode Caenorhabditis elegans, have established that Y. pestis forms a biofilm in the insect. The extracellular matrix of the biofilm seems to contain a homopolymer of N-acetyl-d-glucosamine, which is a constituent of many bacterial biofilms. A regulatory mechanism involved in Y. pestis biofilm formation, cyclic-di-GMP signaling, is also widespread in bacteria; yet only Y. pestis forms biofilms in fleas. Here, the historical background of bubonic plague is briefly described and recent studies investigating the mechanisms by which these unique and deadly biofilms are formed are discussed.


A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin.
This study assessed whether myoinositol might be a first-line medical treatment for gestational diabetes mellitus (GDM). For 12 months, women with GDM not controlled by diet (n=32) were prospectively treated with myoinositol 1200mg and folic acid 400μg/day, while consecutive women (n=28) with insulin-requiring GDM treated during the previous year at our centre constituted the control group. Baseline characteristics and care were similar in both groups. Insulin was required in eight women (25%) in the myoinositol group who, compared with the 24 who did not need insulin, were older (37±5 vs. 32±5 years, respectively; P=0.018) and had a larger percentage of high self-monitored glucose values (45±8% vs. 32±14%; P<0.0001) during the week prior to the introduction of myoinositol treatment. All of the women had similar pregnancy outcomes regardless of their GDM management, although less labour induction was required in the myoinositol group (OR: 0.22 [0.07-0.65]), which had no side effects. This pilot study suggests that myoinositol may be a safe first-line medical treatment for uncontrolled GDM.


Statistical and machine learning methods to study human CD4+ T cell proteome profiles.
Mass spectrometry proteomics has become an important part of modern immunology, making major contributions to understanding protein expression levels, subcellular localizations, posttranslational modifications, and interactions in various immune cell populations. New developments in both experimental and computational techniques offer increasing opportunities for exploring the immune system and the molecular mechanisms involved in immune responses. Here, we focus on current computational approaches to infer relevant information from large mass spectrometry based protein profiling datasets, covering the different steps of the analysis from protein identification and quantification to further mining and modelling of the protein abundance data. Additionally, we provide a summary of the key proteome profiling studies on human CD4+ T cells and their different subtypes in health and disease.


A comparison of AME and CR100 for scaling perceived exertion.
In psychophysical studies of the relation between perceived magnitude and physical stimulus, interest has focused on the preciseness of growth functions. Very little interest has been devoted to natural levels of an "absolute" character and to the validity of direct measurements. In this article, the Category (C)-Ratio (R) (CR) scaling methodology, developed by Borg (1973, 1977, 1982) is presented together with a new CR scale: the CR100 scale. In an experiment on perceived exertion, CR100 was compared with Absolute Magnitude Estimation (AME). Perceived exertion has the advantage of having easily measured physiological variables that can function as validity criteria. 32 persons (16 men and 16 women) participated as subjects on two different occasions, and the presentation order was counterbalanced. Results from CR100 and AME could be described equally well with psychophysical functions. The exponents obtained with CR100 were n = 1.60 for women and n = 1.69 for men, and the corresponding exponents for AME were n = 1.60 for women and n = 1.46 for men (with a "noise" constant included in the function). ANOVA showed that CR100 could make the predicted differentiation between sexes, whereas AME could not. This drawback with AME was also found when using the methods to predict working capacity.


Gender Stereotypes among Teachers and Trainers Working with Adolescents.
Previous scientific literature has not determined the influence exerted by trainers and teachers of adolescents on the development of gender stereotypes in sport. For this reason, the aims of the present research were to establish differences in gender stereotypes in sport among teachers and trainers as a function of profession and sex and to analyze the influence of age and years of experience of male and female trainers and teachers on the gender stereotypes in sport. For this purpose, 127 teachers and trainers completed the questionnaire "gender beliefs and stereotypes towards physical activity and sport". The results showed a significantly higher score of the teachers in "beliefs about physical activity and gender" (p = 0.048) and of the trainers in "physical education classes and gender" (p = 0.006). Concerning sex, women showed higher scores in "sport and gender" (p = 0.005), and men in "beliefs about physical activity and gender" (p = 0.045). Regarding covariates, age showed significant differences in "sport and gender" (p = 0.029), with female teachers showing higher values with respect to female trainers and male teachers, while years of experience showed differences in "beliefs about sport and gender" (p = 0.044), with male teachers showing higher values than male trainers and female teachers.


Sphenoid sinuses' volume and area analysis of Brazilian individuals' CBCTs, related to sex, age, skin color, and nutritional status using DDS-Pro™ software.
The purpose of this study was to analyze the volume and area of sphenoid sinuses of Brazilian individuals' cone-beam computed tomography (CBCT) images using the beta version of the DDS-Pro™ 2.14.2_2022 software (DPP Systems, Czestochowa, Poland), to assess a potential correlation to sex, age, skin color, and nutritional status, and to evaluate differences between the right and left sides. Three-dimensional volume and area measurements were made with the software using CBCT images of 113 living Brazilian individuals of both sexes (67 females and 46 males). TEM, rTEM, and R were used to assess the reproducibility of inter- and intra-examiner measurements. The measurement means were estimated with 95% confidence intervals according to sex and age group. There were no significant differences between the left and right sides for both volume and area and between the sexes and black and white individuals. Volume and area were significantly higher in 18 years or older (p < 0.05) and in individuals with normal body mass index (BMI) (p < 0.05). The obtained results do not allow indicating the use of sphenoid sinuses volume and area measurements to estimate sexual dimorphism, and the same occurred for skin color. However, such measures can help to estimate age. Further studies are suggested with a larger sample, especially for the nutritional status variable.


On the domain-specificity of the visual and non-visual face-selective regions.
What happens in our brains when we see a face? The neural mechanisms of face processing - namely, the face-selective regions - have been extensively explored. Research has traditionally focused on visual cortex face-regions; more recently, the role of face-regions outside the visual cortex (i.e., non-visual-cortex face-regions) has been acknowledged as well. The major quest today is to reveal the functional role of each this region in face processing. To make progress in this direction, it is essential to understand the extent to which the face-regions, and particularly the non-visual-cortex face-regions, process only faces (i.e., face-specific, domain-specific processing) or rather are involved in a more domain-general cognitive processing. In the current functional MRI study, we systematically examined the activity of the whole face-network during face-unrelated reading task (i.e., written meaningful sentences with content unrelated to faces/people and non-words). We found that the non-visual-cortex (i.e., right lateral prefrontal cortex and posterior superior temporal sulcus), but not the visual cortex face-regions, responded significantly stronger to sentences than to non-words. In general, some degree of sentence selectivity was found in all non-visual-cortex cortex. Present result highlights the possibility that the processing in the non-visual-cortex face-selective regions might not be exclusively face-specific, but rather more or even fully domain-general. In this paper, we illustrate how the knowledge about domain-general processing in face-regions can help to advance our general understanding of face processing mechanisms. Our results therefore suggest that the problem of face processing should be approached in the broader scope of cognition in general.


Clinical and genetic factors associated with suicide in mood disorder patients.
Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the 'Psy Pluriel' center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.


Identification of a novel alternatively spliced isoform of the ribosomal uL10 protein.
Alternative splicing is one of the key mechanisms extending the complexity of genetic information and at the same time adaptability of higher eukaryotes. As a result, the broad spectrum of isoforms produced by alternative splicing allows organisms to fine-tune their proteome; however, the functions of the majority of alternatively spliced protein isoforms are largely unknown. Ribosomal protein isoforms are one of the groups for which data are limited. Here we report characterization of an alternatively spliced isoform of the ribosomal uL10 protein, named uL10β. The uL10 protein constitutes the core element of the ribosomal stalk structure within the GTPase associated center, which represents the landing platform for translational GTPases - trGTPases. The stalk plays an important role in the ribosome-dependent stimulation of GTP by trGTPases, which confer unidirectional trajectory for the ribosome, allosterically contributing to the speed and accuracy of translation. We have shown that the newly identified uL10β protein is stably expressed in mammalian cells and is primarily located within the nuclear compartment with a minor signal within the cytoplasm. Importantly, uL10β is able to bind to the ribosomal particle, but is mainly associated with 60S and 80S particles; additionally, the uL10β undergoes re-localization into the mitochondria upon endoplasmic reticulum stress induction. Our results suggest a specific stress-related dual role of uL10β, supporting the idea of existence of specialized ribosomes with an altered GTPase associated center.


Fibrinogen-to-albumin ratio is related to the severity of coronary artery disease in chronic kidney disease patients undergoing coronary angiography.
This study was to explore the potential relationship between the fibrinogen-to-albumin ratio (FAR) and the presence and severity of coronary artery disease (CAD) in stage 3-5 predialysis chronic kidney disease (CKD) patients. This study included 978 patients undergoing coronary angiography (CAG). CAD was defined as the presence of obstructive stenosis>50% of the lumen diameter in any of the four main coronary arteries. Gensini scores (GSs), left main coronary artery (LMCA) and three-vessel coronary artery disease (TVD) were used to elevate the severity of CAD. The adjusted odds ratios of CAD were 3.059 (95% CI: 1.859-5.032) and 2.670 (95% CI: 1.605-4.441) in the third and fourth quartiles of FAR compared with the first quartile, respectively. Among 759 patients diagnosed with CAD, multivariate logistic regression analysis showed that FAR (at the 0.01 level) was significantly positively associated with the presence of LMCA (adjusted OR=1.177, 95% CI 1.067-1.299, P=0.001) or TVD (adjusted OR=1.154, 95% CI 1.076-1.238, P<0.001), and a higher GS (adjusted OR=1.152, 95% CI 1.073-1.238, P<0.001). FAR levels were independently associated with the presence and severity of CAD in stage 3-5 predialysis CKD patients.


Performance of Common Down Syndrome Screening Methods Used in India with Construction of an Indian Normogram for Nuchal Translucency/Crown-Rump Length Measurements in 14,337 Subjects.
Sonologists often lack access to the Fetal Medicine Foundation Down syndrome risk calculation software or cannot offer the combined test for aneuploidy screening because of resource constraints. Instead, sonologists use nuchal translucency (NT) measurements that rely on fixed NT cut-offs for labelling foetuses with high risks for Down syndrome. In the present study, we aimed to plot normative data for NT and the crown-rump length (CRL) in Indian foetuses and to assess the value of using the 95th/99th centiles of NT for CRL cut-offs instead of fixed NT cut-offs to calculate the risk for aneuploidies during the first trimester. We conducted a retrospective observational study measuring the NT/CRL in 14,337 Indian foetuses between 11 and 13 + 6 weeks of gestation. We used regression analysis and calculated the 95th/99th centiles of NT distribution. We compared performances of NT > 95th/99th centiles and fixed NT cut-offs of 2.5- and 3.5-mm as screening. The NT measurements increased with increasing CRL values. NT > 95th centile for a particular CRL for detecting all aneuploidies had the maximum sensitivity of 73.9% for a false positive rate (FPR) of 4.3%. Similar values for fixed cut-off > 2.5 mm were 63.0% FPR 3.7% (T21 68.2 FPR 3.8%) and for NT > 3.5 mm 36.9% FPR 0.43% (T21 36.5% FPR 0.5%). A fixed NT cut-off point is not appropriate for the first trimester screening. The best sensitivity for assessing aneuploidies is achieved using the 95th centile, but the 99th centile achieves higher specificity for gestational age.


Angiotensin-converting enzyme gene polymorphism in North-west Indian children with posterior urethral valves.
To investigate the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and other risk factors with renal scarring in patients with posterior urethral valves (PUV). Forty consecutive patients from North-west India were treated for PUV in 1997-2004. The patients were divided into group 1 (no renal scarring, n=12) and group 2 (renal scars present, n=28) based on dimercato-succinic acid scans. ACE I/D polymorphism was determined by polymerase chain reaction in PUV patients and unrelated healthy controls (n=100). Mean age at presentation was 23.7+/-37.2 months and mean follow up was 4.8+/-1.5 years. Preoperative mean serum creatinine levels for group 1 (non-scarred) and group 2 (scarred) were 1.1+/-1.6 mg/dl and 1.7+/-1.6 mg/dl, respectively. One year after treatment, the serum creatinine levels had decreased to 0.6+/-0.1 mg/dl and 0.8+/-0.3 mg/dl in group 1 and group 2, respectively. ACE genotype distribution in children with PUV was no different from that of controls. The occurrence of D allele was significantly (p=0.04) higher in patients of group 2. Multivariate logistic regression analysis showed that D allele had a significant impact on renal scar formation, introducing a 4.6-fold risk (odds ratio 4.6, 95% confidence interval 1.03-20.38, p=0.04). A highly significant correlation between the occurrence of renal scarring and presence of breakthrough urinary tract infection (odds ratio=7.5, 95% confidence interval 1.60-35.07, p=0.006) and serum creatinine at follow up (odds ratio=0.6, 95% confidence interval 0.47-0.81, p=0.03) was observed. The mean values for glomerular filtration rate (GFR) after 1 year of treatment (p=0.006) and at follow up (p=0.027) were significantly different between the patients with II genotype and ID/DD genotype. Hypertension was observed in 13 patients and proteinuria in nine patients with no significant difference between the patients having II/I D/DD genotypes. The presence of D allele is associated with progression of renal scarring and reduced GFR in PUV patients.


The Analysis of Ethnic Mixtures.
Population of ethnic mixtures can be useful in genetic studies. Admixture mapping, or mapping by admixture linkage disequilibrium (MALD), is specially developed for admixed populations and can supplement traditional genome-wide association analyses in the search for genetic variants underlying complex traits. Admixture mapping tests the association between a trait and locus-specific ancestries. The locus-specific ancestries are in linkage disequilibrium (LD), which is generated by an admixture process between genetically distinct ancestral populations. Because of the highly correlated-locus specific ancestries, admixture mapping performs many fewer independent tests across the genome than current genome-wide association analysis. Therefore, admixture mapping can be more powerful because it reduces the penalty due to multiple tests. In this chapter, we introduce the theory behind admixture mapping and explain how to conduct the analysis in practice.


Failure of Osseointegration of a Semiconstrained Finger Prosthesis in a Post-traumatic Metacarpophalangeal Joint Defect: A Case Report.
Post-traumatic defects of the metacarpophalangeal joint (MCPj) remain challenging for hand surgeons. Restoration of stability and motion are difficult to achieve because of the complex anatomy and kinematics. The Robert Mathys (RM) semiconstrained prosthesis offers good intrinsic stability and mobility and therefore seems suitable. We report on a patient where the RM prosthesis was used for a traumatic destroyed ring finger MCPj reconstruction but failed because of aseptic loosening. We discuss possible reasons in light of the current literature on post-traumatic MCPj arthroplasties and the RM prosthesis in particular. The RM proximal interphalangeal prosthesis does not seem suitable for post-traumatic replacement of the MCPj.


Specific interaction of HLA antibodies (eluates) with washed platelets.
The mechanism of complement-independent action of HLA-A2 antibodies (eluates) on washed platelets was investigated. HLA-specific alteration was confirmed by serological (platelet micro-complement fixation), morphological (platelet spreading) and functional parameters (platelet aggregation, inhibition of collagen-induced platelet aggregation, [14C]serotonin release). In the presence of fibrinogen and calcium ions, HLA antibodies induced instantaneous platelet aggregation and release. Although no morphological (spreading) and functional changes (collagen-induded aggregation) were seen, these platelets did not aggregate or release when fibrinogen was subsequently added. When platelets--in the presence of fibrinogen--were incubated with antibody concentrations too low to induce platelet aggregation or release, specific reduction of platelet reactivity was observed by subsequent collagen aggregation. HLA-specific action of antibodies on washed platelets was inhibited by apyrase and acetyl-salicylic acid, indicating an active participation of platelets in HLA antibody-induced platelet alteration.


Alloiothucha artocarpi (Horvth) (Hemiptera: Heteroptera: Tingidae) found on jackfruit, Artocarpus heterophyllus Lam. (Moraceae): first representative of the genus from Laos, and the synonymy of Cetiothucha Drake amp; Ruhoff.
The lace bug genus Alloiothucha Drake, 1927 (Hemiptera: Heteroptera: Tingidae) is recorded from Laos for the first time with the redescription of Alloiothucha artocarpi (Horvth, 1926), which has been originally described from Indonesia (Java Island) in Latin. This species was collected on jackfruit, Artocarpus heterophyllus Lam. (Moraceae) in Laos, and may represent a pest of potential future concern. An identification key to all described species of Alloiothucha and arguments for a junior synonymy of Cetiothucha is presented: Alloiothucha Drake, 1927 = Cetiothucha Drake Ruhoff, 1965, syn. nov. Two new combinations are proposed: Alloiothucha constanti (Guilbert, Pham Soulier-Perkins, 2018), comb. nov. and Alloiothucha physalia (Drake Ruhoff, 1965), comb. nov. from Cetiothucha.


Association between regional oxygen saturation and central venous saturation in pediatric patients undergoing cardiac surgery: A prospective observational study.
We evaluated the correlation between regional oxygen saturation (rSO2 ) in the frontal and right renal dorsum (cerebral rSO2 and somatic rSO2 ) measured by near-infrared spectroscopy (INVOS™ 5100C, Medtronic) and central venous oxygen saturation (ScvO2 ) measured with a fiber-optic oximetry catheter (PediaSat™, Edwards Lifesciences) during surgery in order to determine whether noninvasive rSO2 could be used as an alternative to ScvO2 in pediatric cardiac surgery patients. We evaluated the correlation between regional tissue oxygen saturation (cerebral rSO2 and somatic rSO2 ) measured by near-infrared spectroscopy and other patient measures with central venous oxygen saturation (ScvO2 ) measured with a fiber-optic oximetry catheter to track global oxygen supply demand as a potential alternative or supplement to ScvO2 . This single-center prospective observational study enrolled 33 children (weight < 10 kg) who underwent cardiac surgery for congenital heart disease between February 2018 and November 2021. ScvO2 , cerebral rSO2 , and somatic rSO2 were recorded simultaneously after anesthesia induction and central venous catheter placement. Pearson's correlation coefficient and Bland-Altman analysis were used to determine the relationship between ScvO2 and rSO2 . We conducted correlation, Bland Altman, and multiple regression analyses to identify associations between rSO2 , patient measures, and ScvO2 values. The patients' median age was 11.0 (quartile 2.0-16.0) months. Their weight was 7.2 (quartile 4.5-9.2) kg. Cerebral rSO2 was significantly positively correlated with ScvO2 (r2 = 0.29, p = .002 in all patients; r2 = 0.61, p = .013 in the patients without mixing at the atrial level), whereas somatic rSO2 was not. The Bland-Altman analysis demonstrated biases [95% confidence interval; 95% CI] (lower and upper limits of agreement [95% CI]) of 0.27% [-4.26 to 4.80] (-24.79 [-32.61 to -16.96] to 25.33 [17.50 to 33.16]) between cerebral rSO2 and ScvO2 and 0.91% [-5.48 to 7.30] (-34.43 [-45.47 to -23.39] to 36.25 [25.21 to 47.29]) between somatic rSO2 and ScvO2 . Preoperative brain natriuretic peptide (BNP) and SpO2 were independent variables associated with ScvO2 and cerebral and somatic rSO2 . Cerebral rSO2 , SpO2 , and BNP were significantly correlated with ScvO2 , although the cerebral rSO2 correlation was greater for lesions without atrial mixing. rSO2 , BNP, and SpO2 might be used to track changes in ScvO2 but cerebral rSO2 is not sufficiently precise to replace it.


Quantitation and characterization of urinary glycosaminoglycans in healthy subjects and patients with mastocytosis.
The urinary glycosaminoglycans (uGAG) in eight patients (four adults and four children) with mastocytosis and eleven healthy subjects (five adults and six children) were examined for evidence of heparin and chondroitin sulfate E. The excretion of uGAG to urinary creatinine (uCr) in these patients was found to be 10.36 micrograms/mg for the children and 0.98 micrograms/mg for the adults, neither significantly different from healthy controls (p greater than 0.2). The uGAG was found to have a molecular mass between 10 kDa and 60 kDa by high performance liquid chromatography (HPLC). The content of the uGAG was found to consist of chondroitin sulfates without any evidence of heparin as assessed by specific chondroitinase ABC susceptibility. Disaccharide analysis following chondroitinase ABC digestion by HPLC Partisil-10 Pac separation revealed no evidence of chondroitin sulfate E and no differences in relative distribution of 0-, 4-, and 6-sulfated disaccharides between patients and healthy controls.


Analysis, Modeling, and Visualization of Chromosome Conformation Capture Experiments.
Chromatin Conformation Capture techniques have unveiled several layers of chromosome organization such as the segregation in compartments, the folding in topologically associating domains (TADs), and site-specific looping interactions. The discovery of this genome hierarchical organization emerged from the computational analysis of chromatin capture data. With the increasing availability of such data, automatic pipelines for the robust comparison, grouping, and classification of multiple experiments are needed. Here we present a pipeline based on the TADbit framework that emphasizes reproducibility, automation, quality check, and statistical robustness. This comprehensive modular pipeline covers all the steps from the sequencing products to the visualization of reconstructed 3D models of the chromatin.


Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure.
The present study aimed to assess specific cognitive processes (cognitive control and time perception) and hemodynamic correlates using functional near-infrared spectroscopy (fNIRS) during acute and prolonged high-altitude exposure. Eleven male subjects were transported via helicopter and dropped at 14 272 ft (4 350 meters) of altitude where they stayed for 4 days. Cognitive tasks, involving a conflict task and temporal bisection task, were performed at sea level the week before ascending to high altitude, the day of arrival (D0), the second (D2) and fourth (D4) day at high altitude. Cortical hemodynamic changes in the prefrontal cortex (PFC) area were monitored with fNIRS at rest and during the conflict task. Results showed that high altitude impacts information processing in terms of speed and accuracy. In the early hours of exposure (D0), participants displayed slower reaction times (RT) and decision errors were twice as high. While error rate for simple spontaneous responses remained twice that at sea level, the slow-down of RT was not detectable after 2 days at high-altitude. The larger fNIRS responses from D0 to D2 suggest that higher prefrontal activity partially counteracted cognitive performance decrements. Cognitive control, assessed through the build-up of a top-down response suppression mechanism, the early automatic response activation and the post-error adjustment were not impacted by hypoxia. However, during prolonged hypoxic exposure the temporal judgments were underestimated suggesting a slowdown of the internal clock. A decrease in cortical arousal level induced by hypoxia could consistently explain both the slowdown of the internal clock and the persistence of a higher number of errors after several days of exposure.


[Work and safety conditions in transportation of patients between hospitals in Denmark].
Questions on the safety and comfort for the staff on interhospital transports were put to assistant matrons of anaesthesiological wards in Denmark. The investigation shows that ambulances leave with unattached equipment on the floor or in the patient's bed and that the staff either sit without safety belts or stand up beside the patient during transport. The ambulance interior is organized in such a way that the staff's working positions are negatively affected.


Expression of chemokine-like factor 1 after focal cerebral ischemia in the rat.
Cerebral ischemic injury is associated with the induction of a series of pro-inflammatory mediators such as cytokines and chemokines. The chemokine-like factor 1(CKLF1), as a novel human cytokine, displays chemotactic activities in a wide spectrum of leukocytes. The present study was conducted to determine if CKLF1 was produced in the brain of rats subjected to transient middle cerebral artery occlusion (TMCAO). Therefore, RT-PCR, Western blot and immunohistochemistry were utilized to characterize the expression of CKLF1 at different times after TMCAO. The result showed that almost no expression of CKLF1 was found in the sham-operated or contralateral cerebral cortex and hippocampus. CKLF1 expression significantly increased in the ischemic cerebral cortex and hippocampus, elevating at 12 h and peaking at 2 days after reperfusion. CKLF1 positive staining was mainly present in the cerebral cortex, hippocampus, thalamus, and hypothalamus. These results demonstrate that the expression of CKLF1 increases after focal cerebral ischemia in rat brain. Thus, CKLF1 may be a potential therapeutic target for cerebral ischemia.


Discriminating ability of spectral domain optical coherence tomography in different stages of glaucoma.
To determine the discriminating ability of retinal nerve fiber layer (RNFL) thickness measured with spectral-domain optical coherence tomography (SD-OCT) in different stages of glaucoma. Thirty normal, 150 glaucomatous eyes were included. Glaucomatous eyes were graded into early, moderate and severe stages according to one of the global indices called visual field index (VFI). Complete ophthalmic examination, white on white perimetry and SD-OCT were done for all patients. RNFL thickness of quadrants and average thickness were recorded. Area under receiver operating characteristic curves (AUCs) were used to assess the performance of OCT parameters. AVERAGE, INFERIOR AND SUPERIOR RNFL THICKNESS WERE THE BEST PARAMETERS TO DISCRIMINATE NORMAL FROM EARLY GLAUCOMA (AUC: 0.91-86), early from moderate (AUC: 0.77-0.70) and moderate from severe (AUC: 0.85-83). Average RNFL loss was 18% in early glaucoma, 28% in moderate glaucoma and 41% in severe glaucoma. Early damage tends to be focal and in the lower quadrant. A significant correlation was detected between mean VFI and mean RNFL loss. Glaucoma was restaged according to average RNFL loss into early: ⩾97.5 μ, moderate: <97.5-72.5 μ and severe: <72.5 μ. RNFL thickness measured with SD-OCT could discriminate the three stages of glaucoma. RNFL loss can be correlated to visual field loss. Future OCT-based staging of glaucoma, adjunctive to perimetry is possible.


Herbal compound "Songyou Yin" attenuates hepatoma cell invasiveness and metastasis through downregulation of cytokines secreted by activated hepatic stellate cells.
Activated hepatic stellate cells (aHSCs) play an important role in the progression of hepatocellular carcinoma (HCC). Here, we determined if cytokines secreted in response to the herbal compound "Songyou Yin" (SYY) treatment of aHSCs could influence invasiveness and metastatic capabilities of hepatoma cells. Primary rat hepatic stellate cells (HSCs) were isolated, activated, divided into SYY treated and untreated (nSYY) groups, and conditioned media (CM-SYY and CM-nSYY, respectively) were collected. The hepatoma cell line, McA-RH7777 was cultured for 4 weeks with SYY, CM-SYY, and CM-nSYY, designated McA-SYY, McA-SYYCM and McA-nSYYCM. The invasiveness and metastatic capabilities were evaluated using Matrigel invasion assay in vitro and pulmonary metastasis in vivo. Matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, N-cadherin, and vimentin protein levels in McA-SYYCM and McA-nSYYCM were evaluated by Western blot. Cytokine levels in conditioned media were tested using enzyme-linked immunosorbent assay (ELISA). Matrigel invasion assay indicated that the number of McA-SYYCM cells passing through the basement membrane was less than in McA-nSYYCM cells (P < 0.01). Similar results were also observed in vivo for lung metastasis. McA-SYYCM cells showed less pulmonary metastasis capabilities than McA-nSYYCM cells (P < 0.001). The reduced expression of MMP-2 and reversed epithelial to mesenchymal transition with E-cadherin upregulation, and N-cadherin and vimentin downregulation were also found in McA-SYYCM compared to McA-nSYYCM. Metastasis-promoting cytokines hepatocyte growth factor, interleukin-6, transforming growth factor-β1, and vascular endothelial growth factor were markedly decreased in CM-SYY compared to CM-nSYY. SYY attenuates hepatoma cell invasiveness and metastasis capabilities through downregulating cytokines secreted by activated hepatic stellate cells.


What If We Don't? A Retrospective Review of Standard Precautions for MRSA.
There are conflicting data in the literature about the need for contact isolation for active methicillin-resistant Staphylococcus aureus (MRSA) infections. In this retrospective review, we compared the MRSA bloodstream standardized infection ratio for 1 year while contact precautions were in place for MRSA infections and for 1 year after routine contact precautions for MRSA were no longer in place. There was no change in the MRSA bloodstream standardized infection ratio between the two time periods. With cessation of contact precautions for MRSA infections, there was no change in bloodstream MRSA standardized infection ratios across a large health system. While standardized infection ratios would not detect asymptomatic horizontal transmission of a pathogen, it is reassuring that bloodstream infections - a known complication of MRSA colonization status - did not rise with cessation of contact precautions.


Interactive multimedia information program for use by breast-care nurses--a patient acceptability study.
To design an interactive multimedia program for use by breast-care nurses and evaluate the acceptability of this technology to patients in the clinical setting. In order to ensure that the clarity of the information was maintained the multimedia program was developed by a multidisciplinary team, including non-medical personnel and patients. A prospective analysis of the subjective impressions of patients with symptomatic breast disorders and breast-care nurses to a multimedia patient information system was then performed using a standard questionnaire and semi-structured interviews. Fifty women were recruited for the study. Thirty-six (72%) considered the multimedia counselling to be superior to the traditional modalities. Forty-nine (98%) graded the system as good or better. No patient regarded the technology as anxiety-provoking or inferior to the traditional leaflet-based approach. Women over 55 years old found the system as acceptable and easy to use as the younger women. The multimedia breast counselling programme was acceptable to patients and was considered superior to the traditional leaflet-based approach by the majority. The inherent advantages of this technology will lead to its increasing utilization in the clinical setting.