Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece.
To assess the hepatitis B virus (HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure (ESRF) patients from Central Greece. Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DNA by real-time polymerase chain reaction. Only serum samples with repeatedly detectable HBV-DNA were considered positive. IgG antibodies to hepatitis C virus (anti-HCV) were tested by a third generation enzyme linked immunosorbent assay (ELISA), while IgG antibodies to hepatitis E virus (anti-HEV) were tested by two commercially available ELISAs. HBV-DNA was detected in 15/366 patients (4.1%) and HBsAg in 20/366 (5.5%). The prevalence of occult HBV infection was 0.9% (3/346 HBsAg-negative patients). Occult HBV was not associated with a specific marker of HBV infection or anti-HCV or anti-HEV reactivity. There was no significant difference in HBV-DNA titres, demographic and biochemical features, between patients with occult HBV infection and those with HBsAg-positive chronic HBV infection. In central Greece, 4% of ESRF patients had detectable HBV-DNA, though in this setting, the prevalence of occult HBV seems to be very low (0.9%).


Comparison of Cardiac Indices Using Two Different Concentrations of Topical Adrenaline during Endoscopic Transsphenoidal Pituitary Surgery: A Prospective Randomized Observational Study.
Introduction Adrenaline-soaked wicks are often employed to decongest nasal mucosa during transsphenoidal pituitary surgeries to ensure proper hemostasis and visibility of the operating field. Considerable debate exists regarding the optimum concentration of adrenaline that strikes a balance between hemostasis as well as the hemodynamic side effects of adrenaline. This study assessed cardiac indices like cardiac output and cardiac index using a FloTrac Vigileo cardiac output monitor to compare two different concentrations of adrenaline used for topical instillation. Materials and Methods 60 adult patients undergoing transsphenoidal pituitary surgery were randomly assigned to receive cotton wicks soaked in adrenaline solution (either 1:100,000 or 1:200,000) for nasal decongestion. Following a standardized anesthetic regime, a FloTrac Vigileo cardiac output monitor was attached with the invasive arterial line for precise monitoring and recording of cardiac indices (cardiac output and cardiac index). Additionally, quality of surgical field (as reported by the operating surgeon) blood loss, incidences of adverse hemodynamic events, and rescue drug usage were recorded. Results No difference in cardiac outputs and cardiac indexes of the patients was observed during baseline to 55 minutes and at 80 minutes and onward, whereas difference rose to statistical significance at the time points of 60 minutes and 70 minutes ( p < 0.05). Other parameters like stroke volume, stroke volume variation, and hemodynamic parameters were similar. Quality of the surgical fields (as reported by the surgeon), intraoperative bleeding, incidences of adverse effects, and frequency of rescue drugs usage were similar. Conclusion Instillation of 1:100,000 dilution of adrenaline solution compared with 1:200,000 for nasal decongestion is associated with significant rise in cardiac output and cardiac index at 60 and 70 minutes of the surgery with similar blood loss and hemodynamic variables. Therefore, the lower concentration of adrenaline can be recommended for usage during transsphenoidal pituitary surgeries.


Bionic Micro-Texture Duplication and RE3+ Space-Selective Doping of Unclonable Silica Nanocomposites for Multilevel Encryption and Intelligent Authentication.
High-capacity optical data storage and information encryption by using glass substrates are fascinating due to merits of expanding the functionality and applicability of the optoelectronic field. However, the development of glass substrate-based multi-dimensional information encryption methods has remained a challenge because of the high hardness, brittleness and melting temperature of glasses. Herein, inspired by the unique natural structure of plant leaves, multicolor micro-texture-based physical unclonable functions (PUFs) fluorescence glass labels (MTPLs) are exploited by using ultraviolet photocurable silica nanocomposites and soft replication method. It is the first time that simultaneous rare-earth ion (RE3+ ) space-selective doping and bionic micro-texture replication onto transparent glass have been realized, in which the doping position and fluorescence color of RE3+ and height information of unclonable micro-texture can be selectively equipped for multilevel information encryption. The prepared micro-scale MTPLs are endowed with tunable multilevel authentication models, including macro-scale multicolor fluorescent 2D patterns, micro-scale pattern, color 3D information and intelligence authentication. A high-performance anti-counterfeiting platform with interactive authentication is also established based on the high robustness and security of MTPLs. Such unclonable bionic MTPLs based on RE3+ space-selective doping and micro-texture duplication provide an effective and potentially universal approach for multilevel encryption and intelligent authentication.


A replication fork determinant for the establishment of sister chromatid cohesion.
Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Cohesion establishment requires acetylation of conserved cohesin lysine residues by Eco1 acetyltransferase. Here, we explore how cohesin acetylation is linked to DNA replication. Biochemical reconstitution of replication-coupled cohesin acetylation reveals that transient DNA structures, which form during DNA replication, control the acetylation reaction. As polymerases complete lagging strand replication, strand displacement synthesis produces DNA flaps that are trimmed to result in nicked double-stranded DNA. Both flaps and nicks stimulate cohesin acetylation, while subsequent nick ligation to complete Okazaki fragment maturation terminates the acetylation reaction. A flapped or nicked DNA substrate constitutes a transient molecular clue that directs cohesin acetylation to a window behind the replication fork, next to where cohesin likely entraps both sister chromatids. Our results provide an explanation for how DNA replication is linked to sister chromatid cohesion establishment.


PML: a generalized monitor of atmospheric turbulence profile with high vertical resolution.
The future generation of extremely large telescopes will be certainly equipped with wide-field adaptive optics systems. All the components of such adaptive optics systems have to be precisely specified, and most of the technical specifications are related to atmospheric turbulence parameters, particularly the profile of the refractive index structure constant Cn2(h). The monitor Profiler of Moon Limb (PML) for the extraction of the Cn2(h) profile with high vertical resolution for nighttime and daytime conditions by the observation of the moon limb or sun edge has been developed and is now routinely exploited at the Calern Observatory on the French Riviera. The PML instrument uses a differential method with two small subapertures through which the moon limb or sun edge are observed, leading to a continuum of double stars that allows a scan of the whole atmosphere with high resolution in altitude. The PML is an autonomous instrument aided by a set of equipment such as an all-sky camera, a small meteorological station, and an automatic system to cover the two subapertures with solar filters to switch from night/moon to day/solar observations. In addition, the PML instrument provides in real time a large characterization of the atmospheric turbulence since it can measure other turbulence parameters, such as the total seeing and the isoplanatic angle.


Prostate brachytherapy with iodine-125 seeds: radiation protection issues.
Brachytherapy for prostate cancer by means of permanently implanted 125I sources is a well established procedure. An increasing number of patients all over the world are treated with this modality. When the technique was introduced at our institution, radiation protection issues relative to this technique were investigated in order to comply with international recommendations and national regulations. Particular attention was paid to the need for patient shielding after discharge from hospital. The effective and equivalent doses to personnel related to implantation, the effective dose to patient relatives as computed by a developed algorithm, the air kerma strength values for the radioactive sources certified by the manufacturer compared with those measured by a well chamber, and the effectiveness of lead gloves in shielding the hands were evaluated. The effective dose to the bodies of personnel protected by a lead apron proved to be negligible. The mean equivalent doses to the physician's hands was 420 microSv for one implant; the technician's hands received 65 microSv. The mean air kerma rate measured at the anterior skin surface of the patient who had received an implant was 55 microGy/h (range, 10-115) and was negligible with lead protection. The measured and certified air kerma strength for125I seeds in RAPID Strand corresponded within a margin of +/- 5%. The measured attenuation by lead gloves in operative conditions was about 80%. We also defined the recommendations to be given to the patient at discharge. The exposure risks related to brachytherapy with 125I to operators and public are limited. However, alternation of operators should be considered to minimize exposure. Patient-related measurements should verify the dose rate around the patient to evaluate the need for shielding and to define appropriate radiation protection recommendations.


Effect of inhaled beclomethasone dipropionate on isocapnic hyperventilation with cold air in asthmatics, measured with forced oscillation technique.
Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, BDP-treated patients showed statistically significant differences in impedance measurements after IHCA, manifested by significant attenuation of resistance at 8 Hz (p<0.01), slope of the frequency-resistance curve (p<0.01), reactance at 8 Hz (p=0.01), and resonant frequency (f0) (p<0.02). Flow-volume recordings showed only a statistically significant change in the decrease of inspiratory vital capacity (IVC) (p=0.01). Furthermore, a significant correlation was observed between serum immunoglobulin E (IgE) levels and the effect of BDP on IHCA, measured with forced oscillation technique. In this study, beclomethasone dipropionate, 1,000 microg x day(-1) for 6 weeks, decreased indirect bronchial hyperresponsiveness as assessed by cold air bronchoprovocation in asthmatic patients. The forced oscillation technique proved a more sensitive method of detecting changes in bronchial tone than flow-volume recordings.


White matter microstructural damage in early treated phenylketonuric patients.
Despite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)). DTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Areas showing abnormal values in the patient group were correlated (Pearson) with age, lifetime Phe values, last year median and mean Phe, concurrent Phe values in plasma, urine neurotransmitters status biomarkers, and with a processing speed task. ETPKU showed bilaterally decreased MD values compared with HCs in the body and splenium of the corpus callosum, superior longitudinal fasciculus, corona radiata and in the posterior limb of the internal capsule. RD values followed a similar pattern, although decreased RD values in PKU patients were also found in the anterior limb of the internal capsule and in the cerebral peduncle. Decreased MD and RD values within the aforementioned regions had significant negative correlations with age, last year median and mean Phe and concurrent Phe values. No correlations were found with monoamines in urine or processing speed task. ETPKU patients showed MD and RD values significantly decreased across the whole brain when compared with HCs, and this damage was associated with high Phe values and the age of patients. Despite this microstructural damage, no affectation in processing speed was observed in patients with good metabolic control. DTI-MRI sequences could be used as a technique to quantify WM damage that is difficult to be detect in T1 or T2-weighted images, but also to quantify damage of WM through the follow up of patients with poor metabolic control in prospective studies.


Analysis of HLA Profiles in 390 Uveitis Cases: Insights into Clinical Presentations.
This study aimed to explain the associations between different types of uveitis and human leukocyte antigen (HLA)-B27, HLA-DR4, and HLA-DRw53. A retrospective analysis of 390 uveitis cases was conducted among inpatients and outpatients diagnosed at Weifang Eye Hospital from 2013 to 2016. All 390 patients underwent HLA-B27 examination, and an additional 40 patients underwent examination for HLA-DR4 and HLA-DRw53. Gender, age, corrected visual acuity (CVA), and recurrence frequency were statistically analyzed based on the onset site and etiology classification. Among the 390 enrolled patients, 206 were male, and 183 were female, with ages ranging from 6 to 87 years (mean: 44.2). The disease onset was classified into anterior uveitis (AU), panuveitis (panU), posterior uveitis (PU), and intermediate uveitis in 180, 112, 88, and 10 cases, respectively. HLA-B27 was positive in 94 cases (53 males and 41 females), yielding a positive rate of 24.1%. In AU patients, 80 (44.4%) tested positive for HLA-B27, while 8 (7.1%) panU patients and 6 PU patients (6.8%) were HLA-B27 positive; none of the intermediate uveitis (IU) patients exhibited HLA-B27 positivity. HLA-B27, HLA-DR4, and HLA-DRw53 examinations were performed on 40 patients with binocular uveitis, resulting in 2 HLA-B27 positive cases, 15 HLA-DR4 positive cases, and 20 HLA-DRw53 positive cases, with positive rates of 5%, 37.5%, and 50%, respectively. Among 25 Vogt Koyanagi-Harada (VKH) cases, 1 tested positive for HLA-B27, 22 were positive for HLA-DR4, and 24 were positive for HLA-DRw53, with positive rates of 4%, 88%, and 96%, respectively. No positive HLA-B27, HLA-DR4, or HLA-DRw53 cases were found among the 10 cases of Behcet's disease (BD). Human leukocyte antigens (HLAs) play a significant role in the mechanism of uveitis. HLA-B27 exhibits high diagnostic value in acute AU, while HLA-DR4 and HLA-DRw53 are crucial for diagnosing binocular uveitis, particularly Vogt Koyanagi-Harada (VKH) syndrome. Further investigation is warranted to explore the relationship between HLA-DR4, HLA-DRw53, and uveitis.


The shape of a hole is perceived as the shape of its interior.
In typical figure-ground displays the figure has shape and is perceived as being in front, whereas the ground is shapeless and recedes to the back. The recent literature on the visual perception of holes has questioned the nature of this coupling between shape and depth both theoretically and empirically. In this paper we provide a theoretical framework that clarifies the underlying issues and we report new evidence supporting the view that the shape of a hole is perceived as the shape of its interior region. Palmer, Davis, Nelson, and Rock (2008 Perception, 37, 1569-1586) showed that the shape of the interior region of a hole is remembered as such, even though the surface visible through it is perceived as farther in depth. The present paper extends this evidence to perceiving holes. Participants performed a speeded shape-matching task in which they compared a surrounded interior region (of either a hole or an object) or its exterior complement with one of several shapes. The results indicate that holes are perceived as shaped in the same way as their material counterparts. We conclude that the shape of a hole is encoded as the shape of its interior region, even though that region contains no surface material. These results can be reconciled with recent experiments that have provided evidence that holes are perceived differently from their material counterparts.


Role of differential mRNA stability in the regulated expression of IgM and IgD.
The expression of IgM and IgD heavy chain mRNA in resting vs activated B cells offers a unique tool for the assessment of the effect of translation on mRNA stability because mu and delta mRNA have identical VDJ sequences but differ substantially in the rest of the molecule. We have shown that despite the 5' UTR identity that allows equal access to the translation machinery, mu mRNA has a significantly higher turnover rate than delta mRNA. However, the short t1/2 of mu mRNA increases significantly after B cell activation. Furthermore, the induction of microS mRNA after B cell activation provides yet another related molecule for comparison. Thus, despite the fact that microS and microM mRNA differ at their 3' ends, they have identical turnover rates in activated B cells. In addition, because the turnover rates of delta mRNA and beta 2 and GAPDH mRNA remain unchanged, these experiments suggest that B cell activation results in the induction of regulatory factor(s) that target specific sequences within mRNA-mu to confer greater stability. They also argue against a more passive regulation of mRNA stability that is a consequence of alterations in the secretory machinery.


Influence of body mass index on growth hormone responses to classic provocative tests in children with short stature.
The diagnosis of growth hormone (GH) deficiency is based on a reduced peak GH response to provocative tests. However, the provocative tests are poorly reproducible and GH secretion is regulated by physiological parameters, such as body weight and puberty. The aim of this study was to assess the influence of body mass index (BMI) on GH response to provocative testing and to analyze the reproducibility of GH stimulation test. Clinical data were collected retrospectively by chart review from the Pediatric Endocrine Unit at the Ajou University Hospital. A total of 187 subjects with short stature who completed a GH stimulation testing between 2003 and 2009 were included in the study. Of the 187 subjects, 66 (35.3%) had GH deficiency, while 121 (64.7%) were categorized as having idiopathic short stature. Reliability was calculated for 48 patients with idiopathic short stature who underwent the GH stimulation test twice. A GH response ≥10 ng/ml after retesting was found in 39 patients (81.3%) and a GH response <10 ng/ml was found in 9 patients (18.7%). In a stepwise multivariate analysis, BMI was a significantly independent predictor of peak GH. Elevated BMI was negatively associated with peak plasma GH levels. The lack of reliability of GH values in response to pharmacological stimuli should be taken into account in the diagnosis of GH deficiency. Also, higher BMI is associated with lower GH secretion. BMI should be measured and GH results appropriately interpreted for all subjects undergoing GH stimulation testing.


New parental positivity: The role of positive emotions in promoting relational adjustment during the transition to parenthood.
The transition to parenthood can be a challenging time for new parent couples, as a baby comes with changes and stress that can negatively influence new parents' relational functioning in the form of reduced relationship satisfaction and disrupted partner social support. Yet, the transition to parenthood is also often experienced as a joyous time. In this research, we draw on the broaden-and-build theory of positive emotions to suggest that new parents' positive emotions are not merely an enjoyable distraction, but are instead central to their relational adjustment. Specifically, we hypothesized that new parents who experienced greater positive emotions would report enhanced relationship satisfaction and partner social support across time. To test these ideas, we drew on two dyadic and longitudinal studies of new parents. In Study 1, 104 couples (208 individuals) completed surveys across the course of 1 year, and in Study 2, 192 couples (384 individuals) completed surveys and a laboratory-based social support interaction over the course of 2 years. At each wave of data collection, participants completed assessments of positive emotions, relationship satisfaction, and partner social support. We examined how actor and partner positive emotions longitudinally predicted relational adjustment across time. Results demonstrated that, even when controlling for baseline levels of each outcome variable, greater actor reports of positive emotions prospectively predicted greater subsequent actor (a) relationship satisfaction, (b) perceptions of social support from the partner, and (c) enacted social support as rated by independent observers, a pattern that was especially prominent for fathers. These results suggest positive emotions may be a resource that fosters healthy relational adjustment during chronically stressful periods that threaten intimate relationships, including during the transition to parenthood. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin.
To investigate the effects of recombinant human erythropoietin on brain oxygenation in a model of diffuse traumatic brain injury. Adult male Wistar rats. Neurosciences and physiology laboratories. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were intravenously administered with either a saline solution or a recombinant human erythropoietin (5000 IU/kg). A third group received no traumatic brain injury insult (sham-operated). Three series of experiments were conducted 2 hours after traumatic brain injury to investigate: 1) the effect of recombinant human erythropoietin on brain edema using diffusion-weighted magnetic resonance imaging and measurements of apparent diffusion coefficient (n = 11 rats per group); local brain oxygen saturation, mean transit time, and blood volume fraction were subsequently measured using a multiparametric magnetic resonance-based approach to estimate brain oxygenation and brain perfusion in the neocortex and caudoputamen; 2) the effect of recombinant human erythropoietin on brain tissue PO₂ in similar experiments (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 rat per group). Compared with the sham-operated group, traumatic brain injury saline rats showed a significant decrease in local brain oxygen saturation and in brain tissue PO₂ alongside brain edema formation and microvascular lumen collapse at H2. Treatment with recombinant human erythropoietin reversed all of these traumatic brain injury-induced changes. Brain perfusion (mean transit time and blood volume fraction) was comparable between the three groups of animals. Our findings indicate that brain hypoxia can be related to microcirculatory derangements and cell edema without evidence of brain ischemia. These changes were reversed with post-traumatic administration of recombinant human erythropoietin, thus offering new perspectives in the use of this drug in brain injury.


External causes and maternal mortality: proposal for classification.
To analyze deaths from external causes and undefined causes in women of childbearing age occurring during pregnancy and early postpartum. The deaths of 399 women of childbearing age, resident in Recife, Northeastern Brazil, in the period 2004 to 2006, were studied. The survey utilized the Reproductive Age Mortality Survey method and a set of standardized questionnaires. Data sources included reports from the Institute of Legal Medicine, hospital and Family Health Strategy records and interviews with relatives of the deceased women. External causes of death during pregnancy were classified according to the circumstance of death, using the O93 code (ICD) and maternal mortality ratios before and after the classification were calculated. Eighteen deaths during pregnancy were identified. The majority were aged between 20 and 29, had between 4 and 7 years of schooling, were black and single parents. Fifteen deaths were classified using the O93 code as pregnancy related death (13 for homicide - code 93.7; 2 by suicide - code 93.6) and three were classified as indirect obstetric maternal deaths (one homicide - code 93.7 and two by suicide - code 93.6). There was an average increment of 35% in the RMM after classification. Deaths from undefined causes in and in early postpartumdid not occur by chance and their exclusion from the calculations of maternal mortality indicators only increases levels of underreporting.


Pharmacological and biochemical interactions of N-(phosphonacetyl)-L-aspartate and 5-fluorouracil in beagles.
N-(Phosphonacetyl)-L-aspartate (PALA) and 5-fluorouracil (FUra) are both antimetabolites that affect the biosynthetic pathways of pyrimidines. To determine whether these two drugs exhibit synergistic pharmacological or biochemical interactions, we determined the pharmacological and biochemical parameters of PALA and [14C]FUra in 14 beagle dogs which received i.v. bolus administrations of either the single agents or the drug combination. The pharmacokinetic parameters of PALA (four dogs, 20 mg/kg) in plasma, cerebrospinal fluid, and urine were not changed by FUra (10 mg/kg, 30 min after PALA). The pharmacokinetics of [2-(14)C]FUra (six dogs, 10 mg/kg, 20 muCi/kg) was characterized by higher FUra plasma concentrations after pretreatment with PALA (20 mg/kg, 30 min before FUra); this led to a significantly larger area under the drug concentration-time curve, a decreased volume of distribution, and a reduced clearance rate and was associated with higher cerebrospinal fluid concentrations of FUra. The FUra plasma and cerebrospinal fluid half-lives, however, were not significantly altered by PALA. The biochemical determinants of PALA and FUra activity were studied in intestinal mucosa, liver, thymus, spleen, and bone marrow of four dogs. Although the activity of the target enzyme of PALA, L-aspartate carbamoyltransferase, in tissue extracts was decreased at least 50% at 18 to 24 hr after PALA administration (50 mg/kg), the uridine nucleotide pools remained remarkably stable. Intracellular FUra concentrations were not influenced by PALA. The incorporation of 5-fluorouridine triphosphate into RNA was enhanced in intestinal mucosa and liver. In other tissues, however, fluorouridine nucleotide concentrations were not affected by PALA. Free 5-fluorodeoxyuridine monophosphate had the highest concentration in liver and was detectable in all tissues, but it was not altered by PALA treatment. Our results show that the pharmacological and biochemical events after FUra exposure are marginally modulated by PALA in normal dogs. If sensitive tumors with a higher degree of interaction between the two drugs could be identified, limited toxicity to normal tissues can be expected.


Environmental glucocorticoids corticosterone, betamethasone and flumethasone induce more potent physiological than transcriptional effects in zebrafish embryos.
Many glucocorticoids occur in the aquatic environments but their adverse effects to fish are poorly known. Here we investigate effects of the natural glucocorticoid corticosterone and the synthetic glucocorticoids betamethasone and flumethasone in zebrafish embryos. Besides studying the effects of each steroid, we compared effects of natural with synthetic glucocorticoids, used as drugs. Exposure at concentrations of 1 μg/L and higher led to concentration-related decrease in spontaneous muscle contractions at 24 h post fertilization (hpf) and increase in heart rate at 48 hpf. Betamethasone showed a significant increase at 0.11 μg/L in heart rate. Corticosterone also accelerated hatching at 60 hpf at 0.085 μg/L. Transcription of up to 24 genes associated with different pathways showed alterations at 96 and 120 hpf for all glucocorticoids, although with low potency. Corticosterone caused transcriptional induction of interleukin-17, while betamethasone caused transcriptional down-regulation of the androgen receptor, aromatase and hsd11b2, indicating an effect on the sex hormone system. Furthermore, transcripts encoding proteins related to immune system regulation (irg1l, gilz) and fkbp5 were differentially expressed by corticosterone and betamethasone, while flumethasone caused only little effects, mainly alteration of the irg1l transcript. Our study shows that these glucocorticoids caused more potent physiological effects in early embryos than transcriptional alterations in hatched embryos, likely due to increased metabolism in later developmental stages. Thus, these glucocorticoids may be of concern for early stages of fish embryos in contaminated aquatic environments.


Effects of dexmedetomidine on performance of bispectral index as an indicator of loss of consciousness during propofol administration.
The performance of bispectral index (BIS) for the measurement of the sedative depth when dexmedetomidine is administered in propofol anaesthesia and sedation has not yet been established. This study evaluated the effects of adjunctive dexmedetomidine on the accuracy of BIS to predict loss of consciousness (LOC) and BIS values predicting LOC during propofol administration. In this randomised, double-blind and placebo-controlled trial, 225 patients scheduled for general anaesthesia were assigned to one of three groups. Dexmedetomidine 0.5 and 1.0 µg kg-1 were intravenously infused for 15 minutes in the dexmedetomidine 0.5 and 1.0 µg kg-1 groups, and saline was infused in the control group. Propofol was administered as an effect-site target-controlled infusion after completion of dexmedetomidine infusion. Patients in each group were allocated to five subgroups in which the concentration of propofol was set at 0, 1, 2, 3 and 4 μg ml-1, respectively. Three minutes after propofol administration, the BIS values and Observer's Assessment of Alertness/Sedation (OAA/S) scores were recorded. There were no significant differences in the prediction probability of BIS for detecting LOC in the three groups. At the time of LOC, BIS50 values were 71.1 and 71.4 in the dexmedetomidine 0.5 and 1.0 µg kg-1 groups, respectively, which were significantly larger than the BIS50 of 63.2 in the control group. The ability of BIS to predict LOC is not influenced by dexmedetomidine during propofol administration, but BIS values are enhanced at the time of LOC.


Serum PAPP-A in normal pregnancy: relationship to fetal and maternal characteristics.
Pregnancy associated plasma protein A (PAPP-A) was measured in maternal serum by electroimmunoassay in 414 women (with subsequent normal pregnancy outcome) during the 38th week of pregnancy. PAPP-A levels were examined in relation to maternal and fetal characteristics, revealing a statistically significant relationship with maternal weight, placental weight, fetal sex and gravidity. The correlation of PAPP-A levels to fetal sex and gravidity could not be explained by differences in placental or maternal weight. Mean levels of PAPP-A were also not significantly different in relation to fetal sex.


Factors related to menopausal symptom management decisions.
To systematically review the literature regarding factors related to women's menopausal symptom management decision making. The PubMed.gov online search engine was queried using pre-selected inclusion and exclusion criteria. Reference lists of articles were also reviewed to identify potentially missed articles. Full-text, English-language, peer-reviewed articles on factors related to menopausal symptom management decisions were reviewed. A total of 16 articles (15 data-based, 1 review of literature) from 6 different countries were reviewed. Most articles were related to decisions about one class of therapies and did not take into account all available therapeutic options. In the 15 data-based articles, diverse methods were used: qualitative (47%), quantitative (47%), and mixed (6%), with most being cross-sectional (93%). Very few of the data-based articles were based on a conceptual model (20%) and none used findings to derive an explanatory or predictive model. Most samples were not representative of special populations, such as women with breast cancer. Factors fell into four broad categories: (1) individual characteristics (demographics, menopause experience, symptomatology); (2) values, attitudes, beliefs, and preferences (attitudes and beliefs about menopause and treatments, preferred modalities, tolerance for risks/side effects); (3) facts and information about menopause and symptom management (amount, type, source, credibility, availability); and (4) health care context (health care provider communication, trust, availability/time, knowledge, relationship). Additional descriptive studies are needed understand women's menopausal symptom management decisions in the context of all available therapies so that a comprehensive model of menopausal symptom management decision making can be specified. Additional understanding is needed regarding decisions in special populations of menopausal women such as breast cancer survivors, a group for whom menopausal symptom management can be particularly complex.


Purification and Characterization of Wheat beta(2-->1) Fructan:Fructan Fructosyl Transferase Activity.
Fructans are the major storage carbohydrate in vegetative tissues of wheat (Triticum aestivum L.). Fructan:fructan fructosyl transferase (FFT) catalyzes fructosyl transfer between fructan molecules to elongate the fructan chain. The objective of this research was to isolate this activity in wheat. Wheat (cv Caldwell) plants grown at 25 degrees C for 3 weeks were transferred to 10 degrees C to induce fructan synthesis. From the leaf blades kept at 10 degrees C for 4 days, fructosyl transferase activity was purified using salt precipitation and a series of chromatographic procedures including size exclusion, anion-exchange, and affinity chromatography. The transferase activity was free from invertase and other fructan-metabolizing activities. Fructosyl transferase had a broad pH spectrum with a peak activity at 6.5. The temperature optimum was 30 degrees C. The activity was specific for fructosyl transfer from beta(2-->1)-linked 1-kestose or fructan to sucrose and beta(2-->1) fructosyl transfer to other fructans (1-FFT). Fructosyl transfer from oligofructans to sucrose was most efficient when 1-kestose was used as donor molecule and declined as the degree of polymerization of the donor increased from 3 to 5. 1-FFT catalyzed the in vitro synthesis of inulin tetra- and penta-saccharides from 1-kestose; however, formation of the tetrasaccharide was greatly reduced at high sucrose concentration. 6-Kestose could not act as donor molecule, but could accept a fructosyl moiety from 1-kestose to produce bifurcose and a tetrasaccharide having a beta(2-->1) fructose attached to the terminal fructose of 6-kestose. The role of this FFT activity in the synthesis of fructan in wheat is discussed.


Passivation of the surface imperfection of TiO2 by using ZIF-8 for efficient carrier separation/transfer.
Photoelectrochemical (PEC) water splitting offers a promising chance for energy generation on a global scale. TiO2 is a widely used photoanode material due to its superior properties and stability. However, the PEC efficiency of TiO2 is usually impeded by the fast recombination of photo-generated electron/hole pairs and the poor charge transfer ability that could be improved by band alignment and imperfection passivation, respectively. Herein, we first report that ZIF-8 is an efficient imperfection passivating layer which acts as a bifunctional cocatalyst for transferring/separating electron/hole pairs for improving the photo/photoelectrochemical performance. This work provides a new insight to investigate the charge interaction mechanism between the interface of TiO2 and ZIF-8.


Preparing parents for NICU discharge: an evidence-based teaching tool.
Preparation for discharge and transition to parents' care of infants hospitalized in the neonatal intensive care unit (NICU) is a process that begins on admission. Identifying parents' educational needs requires thoughtful assessment by experienced nurses. Caring for these infants can be daunting to parents, and participating in a discharge class can be very helpful in easing the transition to home. This article describes a NICU discharge informational DVD/video that was developed to deliver parent education and promote informed and safe transition from hospital to home.


Templating of mesoporous molecular sieves by nonionic polyethylene oxide surfactants.
Mesoporous silica molecular sieves have been prepared by the hydrolysis of tetraethylorthosilicate in the presence of low-cost, nontoxic, and biodegradable polyethylene oxide (PEO) surfactants, which act as the structure-directing (templating) agents. This nonionic, surfactant-neutral, inorganic-precursor templating pathway to mesostructures uses hydrogen bonding interactions between the hydrophilic surfaces of flexible rod- or worm-like micelles and Si(OC(2)H(5))(4-x)(OH)(x) hydrolysis products to assemble an inorganic oxide framework. Disordered channel structures with uniform diameters ranging from 2.0 to 5.8 nanometers have been obtained by varying the size and structure of the surfactant molecules. Metal-substituted silica and pure alumina mesostructures have also been prepared by the hydrolysis of the corresponding alkoxides in the presence of PEO surfactants. These results suggest that nonionic templating may provide a general pathway for the preparation of mesoporous oxides.


An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.
Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.


Can Amlodipine Improve the Pre-ovulatory Follicle Blood Flow in Women with Polycystic Ovarian Syndrome?
A reduction in intra-ovarian vascular resistance is necessary to achieve pregnancy in a natural cycle. The aim of this RCT was to detect whether a vasodilator calcium channel blocker, amlodipine, could increase the pre-ovulatory follicular blood flow, enhance follicular maturation in women with PCOS and improve ovulatory outcome. Sixty women received induction by clomiphene citrate (CC); thirty were given amlodipine (Amlodipine group) and the other 30 women were given placebo (Placebo group). The pattern of pre-ovulatory follicle blood flow was studied by color and power Doppler ultrasonography pre and post drug administration. Independent t-test was used to compare mean values of the 2 groups. The p<0.05 is considered statistically significant. When comparing the Doppler effect of amlodipine versus placebo in the treatment cycle, it was found that mean value of ovarian arteries (OA) pulsatility index was lower in amlodipine group but it didn't reach statistical significance (p= 0.063); however, the mean value of OA resistance index reached statistical significance (p=0.028) in amlodipine group. Moreover, in the second cycle, endometrial thickness was significantly higher (p=0.006) in women of the amlodipine group when compared to those of the placebo group. At least one sonographically detectable mature follicle (≥18 mm) was observed in 54.5% (36/66) during the first cycle. At the second cycle, this proportion significantly rose to 86.7% (26/30) in the amlodipine group, but marginally and non-significantly to 56.7% (17/30) in the placebo group. Amlodipine as calcium channel blocker was proved to have a role in improving ovarian blood flow at the time of ovulation and enhancing follicular maturation and thus, it may increase the chances of conception.


pH regulated anion permeability of aquaporin-6.
The kidney is a model organ for transport physiology (Nielsen 1996). AQPs are well-characterized in mammalian kidneys, where they facilitate transepithelial water reabsorption. Most renal AQPs are expressed either in proximal tubule cells or in collecting duct principal cells, which are known as sites for water reabsorption. AQP1 is present in both apical and basolateral membranes of proximal tubules, and in descending limbs of Henle's loop where 70% of filtrated water is isoosmotically reabsorbed (King and Agre 1996). AQP2 is expressed in principal cells of the collecting duct; in response to vasopressin, AQP2 translocates from intracellular vesicles to the apical plasma membranes, thereby increasing water permeability to concentrate urine (Nielsen et al. 1993, 1995; Knepper 1997; Schrier 2006). AQP3 and AQP4 reside in the basolateral membranes of collecting duct principal cells, where they may provide the exit pathways for urine. AQP7, AQP8, and AQP11 are also present in the proximal tubules (Nielsen et al. 1998).A rat cDNA clone encoding AQP6 was isolated by PCR-based homologous cloning from a rat kidney cDNA library (Ma et al. 1993; Yasui et al. 1999). AQP6 has high sequence homology to AQP0, AQP2, and AQP5. A human AQP6 was also cloned (Ma et al. 1996). Interestingly, the genes encoding AQP2, AQP5, and AQP6 are mapped to chromosome band 12q13 as a family gene cluster at this locus (Ma et al. 1997). Nevertheless, AQP6 is distinct from AQP0, AQP2, and AQP5 in terms of function. Among the renal aquaporins mentioned above, AQP6 has a unique distribution and a distinct function.


Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus.
N-hydroxylating flavin-dependent monooxygenases (FMOs) are involved in the biosynthesis of hydroxamate siderophores, playing a key role in microbial virulence. Herein, we report the first structural and kinetic characterization of a novel alkyl diamine N-hydroxylase DesB from Streptomyces sviceus (SsDesB). This enzyme catalyzes the first committed step in the biosynthesis of desferrioxamine B, a clinical drug used to treat iron overload disorders. X-ray crystal structures of the SsDesB holoenzyme with FAD and the ternary complex with bound NADP+ were solved at 2.86 Å and 2.37 Å resolution, respectively, providing a structural view of the active site environment. SsDesB crystallized as a tetramer and the structure of the individual protomers closely resembles the structures of homologous N-hydroxylating FMOs from Erwinia amylovora (DfoA), Pseudomonas aeruginosa (PvdA), and Aspergillus fumigatus (SidA). Using NADPH oxidation, oxygen consumption, and product formation assays, kinetic parameters were determined for various substrates with SsDesB. SsDesB exhibited typical saturation kinetics with substrate inhibition at high concentrations of NAD(P)H as well as cadaverine. The apparent kcat values for NADPH in steady-state NADPH oxidation and oxygen consumption assays were 0.28 ± 0.01 s-1 and 0.24 ± 0.01 s-1, respectively. However, in product formation assays used to measure the rate of N-hydroxylation, the apparent kcat for NADPH (0.034 ± 0.008 s-1) was almost 10-fold lower under saturating FAD and cadaverine concentrations, reflecting an uncoupled reaction, and the apparent NADPH KM was 33 ± 24 μM. Under saturating FAD and NADPH concentrations, the apparent kcat and KM for cadaverine in Csaky assays were 0.048 ± 0.004 s-1 and 19 ± 9 μM, respectively. SsDesB also N-hydroxylated putrescine, spermidine, and L-lysine substrates but not alkyl (di)amines that were branched or had fewer than four methylene units in an alkyl chain. These data demonstrate that SsDesB has wider substrate scope compared to other well-studied ornithine and lysine N-hydroxylases, making it an amenable biocatalyst for the production of desferrioxamine B, derivatives, and other N-substituted products.


The left-right asymmetry of liver lobation is generated by Pitx2c-mediated asymmetries in the hepatic diverticulum.
Internal organs exhibit left-right asymmetric sizes, shapes and anatomical positions, but how these different lateralities develop is poorly understood. Here we use the experimentally tractable Xenopus model to uncover the morphogenetic events that drive the left-right asymmetrical lobation of the liver. On the right side of the early hepatic diverticulum, endoderm cells become columnar and apically constricted, forming an expanded epithelial surface and, ultimately, an enlarged right liver lobe. In contrast, the cells on the left side become rounder, and rearrange into a compact, stratified architecture that produces a smaller left lobe. Side-specific gain- and loss-of-function studies reveal that asymmetric expression of the left-right determinant Pitx2c elicits distinct epithelial morphogenesis events in the left side of the diverticulum. Surprisingly, the cellular events induced by Pitx2c during liver development are opposite those induced in other digestive organs, suggesting divergent cellular mechanisms underlie the formation of different lateralities.


Proteasome inhibition augments cigarette smoke-induced GM-CSF expression in trophoblast cells via the epidermal growth factor receptor.
Maternal cigarette smoking has adverse effects on pregnancy outcomes. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is an essential cytokine for a normal pregnancy. We investigated the impact of cigarette smoke extract (CSE) on GM-CSF expression in human cytotrophoblast cells and suggested a cellular mechanism underlying the CSE-induced GM-CSF expression. An immortalized normal human trophoblast cell line (B6Tert-1) was treated with CSE. The viability and proliferation of the CSE-treated B6Tert-1 cells were evaluated, and the expression of GM-CSF in these cells was quantified at the mRNA and the protein levels by means of reverse-transcription and quantitative polymerase chain reaction (RT-qPCR); and enzyme-linked immunosorbent assay (ELISA), respectively. Human trophoblast cells treated with CSE had an increased expression of GM-CSF at both the mRNA and the protein levels. The CSE-induced GM-CSF expression was synergistically enhanced by the addition of the proteasome inhibitor MG-132, but inhibited by AG-1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase. Furthermore, CSE treatment increased the phosphorylation of the extracellular-signal regulated kinases (ERK1/2) in the trophoblast cells. The expression of other growth factors such as heparin-binding epidermal growth factor-like growth factor (HB-EGF) and vascular endothelial growth factor (VEGF) was also evaluated. Our data suggested that cigarette smoking and proteasome inhibition synergistically up-regulate GM-CSF cytokine expression by activating the EGFR signaling pathway.


Irritable Bowel Syndrome and Depression: A Shared Pathogenesis.
It is common knowledge that dysfunction of the immune and neuroendocrine systems, in addition to neuroplasticity, is among the pathways that underlie irritable bowel syndrome (IBS) and depression. From as early as the 1950s, the association of IBS with psychiatric disease was postulated; however, the exact mechanism remains elusive. There has been considerable research into the association of IBS and depression over the last years; research into the gut-brain axis and alterations in gut microbes have gained momentum to spell out the relationship between depression and IBS. Evidence from these researchers indicate the dysfunction of homeostatic coping mechanisms; corticotropin-releasing factor appears to be at the core of this dysfunction. The multifactorial etiology of both depression and IBS hinders a universal, one-strategy-fits-all treatment approach to patients with comorbid depression and IBS. This review analyzes the pathophysiology that associates these two conditions; it explores the bidirectional communication between the brain and the gastrointestinal tract, and how these influence the endocrine and immune systems. Review articles, clinical trials and randomized controlled trials that analyzed the association of depression and IBS were identified by searching PubMed, Google Scholar, and articles in PMC databases. Full texts written in English and available via these search engines were selected for the synthesis of this review. Alterations to the gut-brain axis, intestinal microbiota, and the neuro-immune system may be the cornerstone to the association of IBS and depression. This literature review opens alternate therapeutic approaches to comorbid IBS and depression and encourages further research into this topic.


DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity.
Treatment of Diffuse Large B Cell Lymphoma (DLBCL) patients with rituximab and the CHOP treatment regimen is associated with frequent intrinsic and acquired resistance. However, treatment with a CD47 monoclonal antibody in combination with rituximab yielded high objective response rates in patients with relapsed/refractory DLBCL in a phase I trial. Here, we report on a new bispecific and fully human fusion protein comprising the extracellular domains of SIRPα and 4-1BBL, termed DSP107, for the treatment of DLBCL. DSP107 blocks the CD47:SIRPα 'don't eat me' signaling axis on phagocytes and promotes innate anticancer immunity. At the same time, CD47-specific binding of DSP107 enables activation of the costimulatory receptor 4-1BB on activated T cells, thereby, augmenting anticancer T cell immunity. Using macrophages, polymorphonuclear neutrophils (PMNs), and T cells of healthy donors and DLBCL patients, DSP107-mediated reactivation of immune cells against B cell lymphoma cell lines and primary patient-derived blasts was studied with phagocytosis assays, T cell activation and cytotoxicity assays. DSP107 anticancer activity was further evaluated in a DLBCL xenograft mouse model and safety was evaluated in cynomolgus monkey. Treatment with DSP107 alone or in combination with rituximab significantly increased macrophage- and PMN-mediated phagocytosis and trogocytosis, respectively, of DLBCL cell lines and primary patient-derived blasts. Further, prolonged treatment of in vitro macrophage/cancer cell co-cultures with DSP107 and rituximab decreased cancer cell number by up to 85%. DSP107 treatment activated 4-1BB-mediated costimulatory signaling by HT1080.4-1BB reporter cells, which was strictly dependent on the SIRPα-mediated binding of DSP107 to CD47. In mixed cultures with CD47-expressing cancer cells, DSP107 augmented T cell cytotoxicity in vitro in an effector-to-target ratio-dependent manner. In mice with established SUDHL6 xenografts, the treatment with human PBMCs and DSP107 strongly reduced tumor size compared to treatment with PBMCs alone and increased the number of tumor-infiltrated T cells. Finally, DSP107 had an excellent safety profile in cynomolgus monkeys. DSP107 effectively (re)activated innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients.


Safety and technical efficacy of early minimally invasive endoscopy-guided surgery for intracerebral haemorrhage: the Dutch Intracerebral haemorrhage Surgery Trial pilot study.
Previous randomised controlled trials could not demonstrate that surgical evacuation of intracerebral haemorrhage (ICH) improves functional outcome. Increasing evidence suggests that minimally invasive surgery may be beneficial, in particular when performed early after symptom onset. The aim of this study was to investigate safety and technical efficacy of early minimally invasive endoscopy-guided surgery in patients with spontaneous supratentorial ICH. The Dutch Intracerebral Haemorrhage Surgery Trial pilot study was a prospective intervention study with blinded outcome assessment in three neurosurgical centres in the Netherlands. We included adult patients with spontaneous supratentorial ICH ≥10mL and National Institute of Health Stroke Scale (NIHSS) score ≥2 for minimally invasive endoscopy-guided surgery within 8 h after symptom onset in addition to medical management. Primary safety outcome was death or increase in NIHSS ≥4 points at 24 h. Secondary safety outcomes were procedure-related serious adverse events (SAEs) within 7 days and death within 30 days. Primary technical efficacy outcome was ICH volume reduction (%) at 24 h. We included 40 patients (median age 61 years; IQR 51-67; 28 men). Median baseline NIHSS was 19.5 (IQR 13.3-22.0) and median ICH volume 47.7mL (IQR 29.4-72.0). Six patients had a primary safety outcome, of whom two already deteriorated before surgery and one died within 24 h. Sixteen other SAEs were reported within 7 days in 11 patients (of whom two patients that already had a primary safety outcome), none device related. In total, four (10%) patients died within 30 days. Median ICH volume reduction at 24 h was 78% (IQR 50-89) and median postoperative ICH volume 10.5mL (IQR 5.1-23.8). Minimally invasive endoscopy-guided surgery within 8 h after symptom onset for supratentorial ICH appears to be safe and can effectively reduce ICH volume. Randomised controlled trials are needed to determine whether this intervention also improves functional outcome. Clinicaltrials.gov : NCT03608423, August 1st, 2018.


Systematic identification of proteins that elicit drug side effects.
Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause side effects. Of 1428 side effects studied, 732 were predicted to be predominantly caused by individual proteins, at least 137 of them backed by existing pharmacological or phenotypic data. We prove this concept in vivo by confirming our prediction that activation of the serotonin 7 receptor (HTR7) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations.


Changes in the incorporation of carbon derived from glucose into cellular pools during the cell cycle of Saccharomyces cerevisiae.
The rate of incorporation of 14C derived from [U-14C]glucose into cells of Saccharomyces cerevisiae X2180(1B) was investigated as a function of the cell cycle. After pulse-labelling of exponentially growing populations, centrifugal elutriation was used to isolate various cell fractions of increasing cell size, representing successive stages of the cell cycle. The total amount of 14C incorporated per cell was found to increase continuously during the cell cycle along with cellular protein content and Coulter counter cell volume. This pattern supports the model of exponential cell growth. In order to evaluate changes in intracellular carbon flow during the cell cycle, chemical extraction procedures were used to obtain four cellular fractions enriched in either low-molecular-mass components, lipid material, polysaccharides or proteins. The distribution of 14C among these cellular fractions varied during successive stages of the cell cycle, indicating cell-cycle-dependent fluctuations in intracellular carbon flow. During the G1 phase the flow of 14C into the low-molecular-mass pool increased markedly; concurrently, the rate of incorporation into the polysaccharide-enriched pool decreased.


Structure of 2',3'-di-O-acyl-alpha-D-glucopyranosyl-(1 leads to 2)-D-glyceric acid, a new glycolipid from Nocardia caviae.
The structure of a new glycolipid isolated from the acetone-soluble lipids of the strain of Nocardia caviae has been determined. The water-soluble moiety contains one mole of D-glucose and one mole of D(-)-glyceric acid; the lipid moiety is a mixture of myristic, palmitic and stearic acids with small amounts of oleic acid. The structure of the deacylated compound was determined by periodate oxidation, methylation and enzymatic degradation. The localization of fatty acid residues at 2',3' on glucose was established by methylation and mass spectrometry. The structure was confirmed by 13C NMR spectrometry of the glycolipid and of the deacylated compound. This glycolipid is a 2'.3'-di-O-acyl-alpha-D-glucopyranosyl-(1 leads to 2)-D-(-)-glyceric acid.


Has managed care changed the skills required for physicians to practice medicine?
Are the skills taught in medical school sufficient for running a practice under managed care? Of 784 physicians randomly sent a questionnaire posing this and other questions, 94 percent agreed that managed care has changed the constellation of skills needed by physicians. Specifically useful to know are business administration skills, said 89 percent; and 59 percent felt business administration skills would directly enhance patient treatment.


The effect of light on the gravimorphogenesis of cucumber seedlings.
Light affects the responses of plants to gravity. For example, light is inhibitory to the gravimorphogenesis of cucumber seedlings, peg formation. We have suggested that auxin regulates peg formation by stimulating the expression of auxin-inducible genes including CsACS1 that encodes key enzyme in ethylene synthesis. We also have hypothesized that ethylene promotes the development of peg in cucumber seedlings. To understand how light inhibits peg formation, we examined the effects of light on the auxin-induced peg formation, the expression of auxin-inducible genes and ethylene production in cucumber seedlings. Number of seedlings that produced a peg in response to applied IAA was significantly decreased by exposure to light compared with that in the dark. In addition, exposure of seedlings to light decreased mRNA accumulation of CsACS1 and ethylene production. However ethylene application did not compensate the inhibition of peg formation by light. These results suggest that light blocks auxin-mediated step(s) including CsACS1 expression for the initiation of peg formation.


Visual pigments of Baltic Sea fishes of marine and limnic origin.
Absorbance spectra of rods and some cones were measured by microspectrophotometry in 22 fish species from the brackish-water of the Baltic Sea, and when applicable, in the same species from the Atlantic Ocean (3 spp.), the Mediterranean Sea (1 sp.), or Finnish fresh-water lakes (9 spp.). The main purpose was to study whether there were differences suggesting spectral adaptation of rod vision to different photic environments during the short history (<10(4) years) of postglacial isolation of the Baltic Sea and the Finnish lakes. Rod absorbance spectra of the Baltic subspecies/populations of herring (Clupea harengus membras), flounder (Platichthys flesus), and sand goby (Pomatoschistus minutus) were all long-wavelength-shifted (9.8, 1.9, and 5.3 nm, respectively, at the wavelength of maximum absorbance, lambda(max)) compared with their truly marine counterparts, consistent with adaptation for improved quantum catch, and improved signal-to-noise ratio of vision in the Baltic light environment. Judged by the shape of the spectra, the chromophore was pure A1 in all these cases; hence the differences indicate evolutionary tuning of the opsin. In no species of fresh-water origin did we find significant opsin-based spectral shifts specific to the Baltic populations, only spectral differences due to varying A1/A2 chromophore ratio in some. For most species, rod lambda(max) fell within a wavelength range consistent with high signal-to-noise ratio of vision in the spectral conditions prevailing at depths where light becomes scarce in the respective waters. Exceptions were sandeels in the Baltic Sea, which are active only in bright light, and all species in a "brown" lake, where rod lambda(max) lay far below the theoretically optimal range.


Postoperative external beam radiotherapy for differentiated thyroid cancer: outcomes and morbidity with conformal treatment.
To review institutional outcomes for patients treated for differentiated thyroid cancer with postoperative conformal external beam radiotherapy (EBRT). This is a single-institution retrospective review of 131 consecutive patients with differentiated thyroid cancer who underwent EBRT between January 1996 and December 2005. Histologic diagnoses included 104 papillary, 21 follicular, and six mixed papillary-follicular types. American Joint Committee on Cancer stage distribution was Stage III in 2 patients, Stage IVa-IVc in 128, and not assessable in 1. Thirty-four patients (26%) had high-risk histologic types and 76 (58%) had recurrent disease. Extraglandular disease spread was seen in 126 patients (96%), microscopically positive surgical margins were seen in 62 patients (47%), and gross residual disease was seen in 15 patients (11%). Median EBRT dose was 60 Gy (range, 38-72 Gy). Fifty-seven patients (44%) were treated with intensity-modulated radiotherapy (IMRT) to a median dose of 60 Gy (range, 56-66 Gy). Median follow-up was 38 months (range, 0-134 months). Kaplan-Meier estimates of locoregional relapse-free survival, disease-specific survival, and overall survival at 4 years were 79%, 76%, and 73%, respectively. On multivariate analysis, high-risk histologic features and gross residual disease predicted for inferior locoregional relapse-free survival, whereas high-risk histologic features, M1 disease, and gross residual disease predicted for inferior disease-specific and overall survival. The IMRT did not impact on survival outcomes, but was associated with less frequent severe late morbidity (12% vs. 2%). Postoperative conformal EBRT provides durable locoregional disease control for patients with high-risk differentiated thyroid cancer if disease is reduced to microscopic burden. Patients with gross disease face significantly worse outcomes. The IMRT may significantly reduce chronic radiation morbidity, but requires additional study.


Evaluating Mechanisms of Postoperative Delirium and Cognitive Dysfunction Following Elective Spine Surgery in Elderly Patients (CONFESS): Protocol for a Prospective Observational Trial.
Elderly people are at particular high risk for postoperative delirium (POD) following spine surgery, which is associated with longer hospital stays, higher costs, risk for delayed complications, long-term care dependency, and cognitive dysfunction (POCD). It is insufficiently understood which mechanisms and risk factors contribute to the development of POD and POCD following these major but plannable surgeries. This study aims to identify modifiable risk factors in spine surgery. A better understanding thereof would help adapt medical management and surgical strategies to individual risk profiles. This is a single-center observational study jointly conducted by the departments of neurosurgery, neurology, and anesthesiology at a tertiary care hospital in Germany. All patients aged 60 years and older presenting to the neurosurgery outpatient clinic or ward for elective spine surgery are screened for eligibility. Exclusion criteria include presence of neurodegenerative or history of psychiatric disease and medication with significant central nervous system activity (eg, antidepressants, antipsychotics, sedatives). Surgical and anesthetic procedures including duration of surgery as primary end point of this study are thoroughly documented. All patients are furthermore evaluated for their preoperative cognitive abilities by a number of tests, including the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery. Physical, mental, and social health and well-being are assessed using the Patient-Reported Outcome Measurement Information System Profile 29 and Hospital Anxiety and Depression Scale. Patients additionally receive preoperative cerebrovascular ultrasound and structural and functional brain imaging. The immediate postoperative period includes screening for POD using the Nursing Delirium Screening Scale and validation through Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria. We furthermore investigate markers of (neuro)inflammation (eg, interleukins, C-reactive protein, tumor necrosis factor alpha). Preoperative examinations are repeated 3 months postoperatively to investigate the presence of POCD and its mechanisms. Statistical analyses will compare delirious and nondelirious patients for predictors of immediate (POD) and delayed (POCD) cognitive dysfunction. This is the first study to prospectively evaluate risk factors for POD and POCD in spine surgery. Recruitment is ongoing, and data collection is estimated to be finished with the inclusion of 200 patients by mid-2020. The identification of mechanisms, possibly common, underlying POD and POCD would be a major step toward defining effective interventional strategies early in or even before the postoperative period, including the adaptation of surgical strategies to individual risk profiles. ClinicalTrials.gov NCT03486288; https://clinicaltrials.gov/ct2/show/NCT03486288. DERR1-10.2196/15488.


Continuous motion analysis of the head-neck complex under impact.
The objective of the present study was to analyze the localized kinematic biodynamics of the human head-neck complex under impact loading. Unembalmed human cadaveric head-neck complexes were subjected to axial compressive forces delivered using an electrohydraulic testing device. The head-neck complex was aligned along the stiffest-axis; musculature was simulated using preloaded springs and cables; and retroreflective targets were inserted into the vertebral body, the facet joint articulation, and the spinous process at every level of the cervical column. At dynamic loading rates (1.8-5.1 m/min), mid to lower cervical spine injuries consistently occurred in these preparations. Continuous motion analysis of the components (vertebral body, intervertebral disk, facet joint, and the spinous process) at all levels of the cervical spine showed the temporal order of the transfer of the external load. Injuries documented by computed tomography and cryomicrotomy techniques correlated with the kinematics of the structure. The application of dynamic loading to the head-neck complex coupled with high-speed, continuous-motion analysis of the intervertebral components of the entire cervical column makes possible the definition of the temporal kinematic mechanics that are fundamental to the understanding of the biodynamics of cervical spine trauma. Using these procedures, we have correlated the kinematics with the onset and pattern of neck injury secondary to impact forces.


Brain Functional Effects of Psychopharmacological Treatment in Major Depression: a Focus on Neural Circuitry of Affective Processing.
In the last two decades, neuroimaging research has reached a much deeper understanding of the neurobiological underpinnings of major depression (MD) and has converged on functional alterations in limbic and prefrontal neural networks, which are mainly linked to altered emotional processing observed in MD patients. To date, a considerable number of studies have sought to investigate how these neural networks change with pharmacological antidepressant treatment. In the current review, we therefore discuss results from a) pharmacological functional magnetic resonance imaging (fMRI) studies investigating the effects of selective serotonin or noradrenalin reuptake inhibitors on neural activation patterns in relation to emotional processing in healthy individuals, b) treatment studies in patients with unipolar depression assessing changes in neural activation patterns before and after antidepressant pharmacotherapy, and c) predictive neural biomarkers of clinical response in depression. Comparing results from pharmacological fMRI studies in healthy individuals and treatment studies in depressed patients nicely showed parallel findings, mainly for a reduction of limbic activation in response to negative stimuli. A thorough investigation of the empirical findings highlights the importance of the specific paradigm employed in every study which may account for some of the discrepant findings reported in treatment studies in depressed patients.


From starphenes to non-benzenoid linear conjugated polymers by substrate templating.
Combining on-surface synthetic methods with the power of scanning tunneling microscopy to characterize novel materials at the single molecule level, we show how to steer the reactivity of one anthracene-based precursor towards different product nanostructures. Whereas using a Au(111) surface with three-fold symmetry results in the dominant formation of a starphene derivative, the two-fold symmetry of a reconstructed Au(110) surface allows the selective growth of non-benzenoid linear conjugated polymers. We further assess the electronic properties of each of the observed product structures via tunneling spectroscopy and DFT calculations, altogether advancing the synthesis and characterization of molecular structures of notable scientific interest that have been only scarcely investigated to date, as applies both to starphenes and to non-benzenoid conjugated polymers.


Facts and fiction about sulfur metabolism in relation to plant-pathogen interactions.
Sulfur deficiency developed into a widespread nutrient disorder in the 1980s because of the drastic decrease of SO(2) emissions in western Europe after Clean Air Acts came into force. It was observed that not only the yield and quality of agricultural crops were negatively affected by sulfur deficiency but also their health status. Since the mid 1990s the physiological background of this latter phenomenon in the sulfur metabolism has been studied by different researchers. From 2001 until 2006, field trials with different varieties of oilseed rape were conducted in Germany, and also from 2001 until 2003 in Scotland, to investigate the underlying mechanisms of sulfur-induced resistance and to develop fertiliser strategies which increase the health status of crops and minimise the requirement for chemical fungicides. A comprehensive disease assessment was conducted and a range of different sulfur-containing metabolites and enzymes were analysed in relation to sulfur nutrition and fungal diseases. H2S emissions from field-grown crops under different sulfur nutritional status were studied for the first time and a positive relationship was observed. Besides S fertilisation, fungal infection increased H2S emissions, too. The studies deliver new insight into the complex of sulfur-induced resistance but many questions still remain open. This contribution will show different possible strategies to solve some of the open questions.


Electron microscopic immunocytochemical localization of myelin proteolipid protein and myelin basic protein to oligodendrocytes in rat brain during myelination.
Electron microscopic immunocytochemical studies were carried out to localize myelin basic protein and myelin proteolipid protein during the active period of myelination in the developing rat brain using antisera to purified rat brain myelin proteolipid protein and large basic protein. The anti-large basic protein serum was shown by the immunoblot technique to cross-react with all five forms of basic protein present in the myelin of 8-day-old rat brain. Basic protein was localized diffusely in oligodendrocytes and their processes at very early stages in myelination. The immunostaining for basic protein was not specifically associated with any subcellular structures or organelles. The ultrastructural localization of basic protein suggests that it may be involved in fusion of the cytoplasmic faces of the oligodendrocyte processes during compaction of myelin. Immunoreactivity in the oligodendrocyte and myelin due to proteolipid protein appeared at a later stage of myelination than did that due to basic protein. Staining for proteolipid protein in the oligodendrocyte was restricted to the membranes of the rough endoplasmic reticulum, the Golgi apparatus, and apparent Golgi vesicles. The early, uncompacted periaxonal wrappings of oligodendrocyte processes were well stained with antiserum to large basic protein whereas staining for proteolipid protein was visible only after the compaction of myelin sheaths had begun. Our evidence indicates that basic protein and proteolipid protein are processed differently by the oligodendrocytes with regard to their subcellular localization and their time of appearance in the developing myelin sheath.


Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta.
Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose-dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5-fold higher) than that needed to obtain 29 nmol/L of HgCl2 on the vascular function. Three-month-old male Wistar rats received intramuscular (i.m.) HgCl2 for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l-NAME (100 μmol/L). The phosphorylated-eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE-induced contractions, while l-NAME had no effects and indomethacin (10 μmol/L), losartan (10 μmol/L) and apocynin (30 μmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase-2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin-angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.


[Nurse perceptions of patient safety in ICU].
Patient safety and error prevention have developed as a new dimension in nursing over the last decade. Using qualitative research methods we have been able to identify twenty-five scenarios and activities prone to errors. Participant nurses believed safety could be improved in each one of the scenarios. The riskier activities are related to hand written documentation, drug handling, sign outs, lack off appropriate training, and lack off multidisciplinary meetings. Our paper describes Intensive Care Unit (ICU) safety from the nursing point of view.


[The unitary strategy of cancer cells: the hydrogen ion as a multidimensional unitary factor and carbohydrate metabolism (2)].
A systematic outlook of metabolism regarding the strategy followed by cancer cells is necessary in order to understand the thermodynamic advantages of these cells and the difficulty found in the treatment of certain malignant diseases. These features show that the present-day vision, the biochemical-analytical-fragmentary-reduccionistic approach, is not and it is not likely that it wil never be sufficient. Thus, a new paradigm of a different dimension but a the same time complementary to the previous and actual one seems necessary. Therefore, a higher and more comprehensive and outreaching vision, transbiochemical and metaenzymatic, one ecologically and macro and microenvironmentally oriented and finally synthetic and unitary one, appears mandatory. The dynamics of the hydrogen ion as applied to biological processes seems to be able to offer the opportunity to arrive to such kind of unifying comprehension through an integrated perceptive model at multiple levels of biological, biomedical and biophysical understanding.


Gene expression signature with independent prognostic significance in epithelial ovarian cancer.
Currently available clinical and molecular prognostic factors provide an imperfect assessment of prognosis for patients with epithelial ovarian cancer (EOC). In this study, we investigated whether tumor transcription profiling could be used as a prognostic tool in this disease. Tumor tissue from 68 patients was profiled with oligonucleotide microarrays. Samples were randomly split into training and validation sets. A three-step training procedure was used to discover a statistically significant Kaplan-Meier split in the training set. The resultant prognostic signature was then tested on an independent validation set for confirmation. In the training set, a 115-gene signature referred to as the Ovarian Cancer Prognostic Profile (OCPP) was identified. When applied to the validation set, the OCPP distinguished between patients with unfavorable and favorable overall survival (median, 30 months v not yet reached, respectively; log-rank P = .004). The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. The hazard ratio for death in the unfavorable OCPP group was 4.8 (P = .021 by Cox proportional hazards analysis). The OCPP is an independent prognostic determinant of outcome in EOC. The use of gene profiling may ultimately permit identification of EOC patients appropriate for investigational treatment approaches, based on a low likelihood of achieving prolonged survival with standard first-line platinum-based therapy.


Magnetosomes eliminate intracellular reactive oxygen species in Magnetospirillum gryphiswaldense MSR-1.
Magnetotactic bacteria synthesize magnetic particles called magnetosomes that cause them to orient to their external magnetic fields. However, the physiological significance and other possible functions of these magnetosomes have not been explored in detail. In this study, we have investigated the biological functions of magnetosomes with respect to their ability to scavenge reactive oxygen species (ROS) in Magnetospirillum gryphiswaldense MSR-1. To assess the changes in ROS levels under different conditions, cells were cultured under aerobic or micro-aerobic conditions in medium containing high and low amounts of iron. To ensure that the observed results were not due to nonspecific interactions, reactions were carried out using a mutant deficient in synthesizing magnetite (mamO-deficient mutant), its complementary strain or the wild-type MSR-1. We observed that the levels of intercellular ROS under micro-aerobic conditions with high-iron medium were much higher when the non-synthetic Fe(3) O(4) crystals mutant Mu21-415 was employed for the assay, compared with the wild-type or complementary strain, or when conditions were aerobic with low-iron medium. These results indicated that magnetosomes function in the scavenging of intracellular ROS. Furthermore, we have demonstrated that the magnetosomes exhibit peroxidase-like properties, by using the earlier reported in vitro horseradish peroxidase assay for artificial magnetic nanoparticles. In addition to possessing peroxidase-like activity, the magnetosomes also exhibited a more enzymatic kinetic response, suggesting that proteins on the membranes of the magnetosomes likely contribute to the enzymatic activity. This is the first study to demonstrate that magnetosomes play an important role in decreasing or eliminating ROS.


Minimally Invasive and Endoscopic Approach to Esophageal Perforation.
Although esophageal perforation is rare, it is a life-threatening condition. The esophagus is very sensitive to rupture and perforation due to the absence of a serosal layer. More than half of the esophageal perforations are iatrogenic and most occur during endoscopy. Around 55% of esophageal injuries occur in the intrathoracic region, 25% in the cervical region, and 20% in the abdominal region. Clinical manifestations and mortality are related to various components such as the etiology, localization, type of injury, severity of contamination, injury to adjacent mediastinal structures, and time from perforation to treatment. When perforation occurs in the esophagus, saliva, stomach contents, bile fluid, and other secretions may pass into the mediastinum causing mediastinal emphysema, inflammation followed by mediastinal necrosis, and chemical mediastinitis. Early clinical suspicion and imaging are essential for successful treatment. Despite advances in technology and treatment, the morbidity and mortality rate due to esophageal perforation is still higher than 20% according to the reported studies. Until now, the main treatment of esophageal perforation was the surgical approach. Nowadays, endoluminal procedures such as endoscopic vacuum therapy, endoscopic stent placement, endoscopic clip closure, endoscopic suturing, and tissue adhesives have started to be applied more. In this review, the minimally invasive and endoscopic approach methods suitable for esophageal perforation according to the characteristics of the patients and the structure of the perforation were examined.


p53 suppression overwhelms DNA polymerase eta deficiency in determining the cellular UV DNA damage response.
Xeroderma pigmentosum variant (XP-V) cells lack the damage-specific DNA polymerase eta and have normal excision repair but show defective DNA replication after UV irradiation. Previous studies using cells transformed with SV40 or HPV16 (E6/E7) suggested that the S-phase response to UV damage is altered in XP-V cells with non-functional p53. To investigate the role of p53 directly we targeted p53 in normal and XP-V fibroblasts using short hairpin RNA. The shRNA reduced expression of p53, and the downstream cell cycle effector p21, in control and UV irradiated cells. Cells accumulated in late S phase after UV, but after down-regulation of p53 they accumulated earlier in S. Cells in which p53 was inhibited showed ongoing genomic instability at the replication fork. Cells exhibited high levels of UV induced S-phase gammaH2Ax phosphorylation representative of exposed single strand regions of DNA and foci of Mre11/Rad50/Nbs1 representative of double strand breaks. Cells also showed increased variability of genomic copy numbers after long-term inhibition of p53. Inhibition of p53 expression dominated the DNA damage response. Comparison with earlier results indicates that in virally transformed cells cellular targets other than p53 play important roles in the UV DNA damage response.


Applications of artificial intelligence and machine learning in respiratory medicine.
The past 5 years have seen an explosion of interest in the use of artificial intelligence (AI) and machine learning techniques in medicine. This has been driven by the development of deep neural networks (DNNs)-complex networks residing in silico but loosely modelled on the human brain-that can process complex input data such as a chest radiograph image and output a classification such as 'normal' or 'abnormal'. DNNs are 'trained' using large banks of images or other input data that have been assigned the correct labels. DNNs have shown the potential to equal or even surpass the accuracy of human experts in pattern recognition tasks such as interpreting medical images or biosignals. Within respiratory medicine, the main applications of AI and machine learning thus far have been the interpretation of thoracic imaging, lung pathology slides and physiological data such as pulmonary function tests. This article surveys progress in this area over the past 5 years, as well as highlighting the current limitations of AI and machine learning and the potential for future developments.


Effects of diet and exercise training on thermogenesis in adult female rats.
The effects of a cafeteria diet on body weight gain, food intake, resting metabolic rate (RMR) and the thermic effect of food (TEF) were compared in female Charles River albino rats that were either sedentary or exercise-trained. The food intakes of the exercise-trained rats on the cafeteria diet were increased to the same degree as those of the sedentary rats, however, they gained less body weight and body fat than sedentary controls. The exercise training increased RMR independent of diet, but differentially increased TEF in rats given the cafeteria diet. Conversely, sedentary rats on the cafeteria diet had significantly lower RMR, but their TEF were not different from control animals on lab chow. Thus, in addition to the direct cost of the exercise, training increased thermogenesis (RMR and TEF) which also helped prevent the dietary obesity which normally occurs with cafeteria diets.


Longevity and reproductive comparisons for male ACI and Sprague-Dawley rat aging colonies.
ACI male rats had a life span approximately one-half year greater than that of Sprague-Dawley male rats. For ACI male rats, median survival was 31.5 months for virgins and 30 months for breeders; for Sprague-Dawley male rats, median survival was 24.5 months for virgins and 25 months for breeders. There was increased fertility of aged ACI males relative to Sprague-Dawley males. ACI males, approximately 2 years old, sired an average of 3.8 litters during a 6-month breeding period, while Sprague-Dawley males of similar age sired an average of 0.9 litters within an equivalent period.


[Usefulness of fetal biophysical profile in preterm rupture of membranes with treatment].
To evaluate the usefulness of the fetal biophysical profile as a predictor of early neonatal infection in patients with preterm rupture of membranes in conservative management. This is a validation study of a diagnostic test. Between November, 2001 and August, 2003, 75 patients with 27 to 33 weeks of gestation and preterm rupture of membranes in conservative management were studied. Daily, a fetal biophysical profile was applied to them. Statistical analysis was done with chi square test and with a 2 x 2 contingency table that compared the biophysical score of + 8 and < or = 6 versus the presence or absence of early neonatal infection. The biophysical score < or = 6 was associated with early neonatal infection (p < 0.05), with sensitivity, specificity, positive and negative predictive values of 80, 85, 64 and 85%, respectively (OR 9.73, 95% CI: 2.88-34.63; p = 0.0000164). The biophysical score < or = 6 was significantly associated with early neonatal infection.


Physiological responses and toxin production of Microcystis aeruginosa in short-term exposure to solar UV radiation.
The aim of this study was to evaluate the effects of short-term (hours) exposure to solar UV radiation (UVR, 280-400 nm) on the physiology of Microcystis aeruginosa. Three solar radiation treatments were implemented: (i) PAR (PAR, 400-700 nm), (ii) TUVA (PAR + UVAR, 315-700 nm) and (iii) TUVR (PAR + UVAR + UVBR, 280-700 nm). Differential responses of antioxidant enzymes and the reactive oxygen species (ROS) production to UVR were observed. Antioxidant enzymes were more active at high UVR doses. However, different responses were observed depending on the exposure to UVAR or UVBR and the dose level. No effects were observed on the biomass, ROS production or increased activity of superoxide dismutase (SOD) and catalase (CAT) compared to the control when UVR + PAR doses were lower than 9875 kJ m-2. For intermediate doses, UVR + PAR doses between 9875 and 10 275 kJ m-2, oxidative stress increased while resistance was imparted through SOD and CAT in the cells exposed to UVAR. Despite the increased antioxidant activity, biomass decrease and photosynthesis inhibition were observed, but no effects were observed with added exposure to UVBR. At the highest doses (UVR + PAR higher than 10 275 kJ m-2), the solar UVR caused decreased photosynthesis and biomass with only activation of CAT by UVBR and SOD and CAT by UVAR. In addition, for such doses, a significant decrease of microcystins (MCs, measured as MC-LR equivalents) was observed as a consequence of UVAR. This study facilitates our understanding of the SOD and CAT protection according to UVAR and UVBR doses and cellular damage and reinforces the importance of UVR as an environmental stressor. In addition, our results support the hypothesized antioxidant function of MCs.


Clinicopathological Significances and Prognostic Value of PPFIA4 in Colorectal Cancer.
Purpose: The PPFIA gene family (PPFIA1, PPFIA2, PPFIA3, and PPFIA4) is associated with multiple human diseases, particularly malignant tumors. However, the expression and prognostic value of the PPFIA family in human colorectal cancers (CRCs) have not been reported. Materials and methods: In this study, several databases, including Oncomine, UALCAN, and the cancer cell line encyclopedia, were used to compare differences in PPFIA1, PPFIA2, PPFIA3, and PPFIA4 expression between normal colon samples and CRCs. The expression levels of these four proteins were used to evaluate the survival of patients with CRC, as determined by the Cancer Genome Atlas Program (TCGA) portal and gene expression profiling interactive analysis (GEPIA) databases. Western blotting and reverse transcription-polymerase chain reaction were performed to detect protein and mRNA levels of PPFIA1, PPFIA3, and PPFIA4, respectively. Immunohistochemical (IHC) staining was used to detect the correlation between PPFIA4 expression and the degree of CRC malignancy. Furthermore, potential miRNAs targeting PPFIA4 in CRCs were studied and confirmed. Results: Bioinformatic analysis showed that the mRNA levels of PPFIA1, PPFIA3, and PPFIA4 were higher in CRC tissue samples than in normal colon tissue. Both mRNA and protein expression of PPFIA1, PPFIA3, and PPFIA4 were increased in the CRC cell lines LoVo and Hct116 compared with the normal colon epithelial cell line. Only PPFIA4 was associated with the prognosis of patients with CRC, which was confirmed by TCGA portal and GEPIA. IHC staining confirmed that the expression of PPFIA4 was higher in CRC tissues than in normal colon tissues and also increased in poorly differentiated CRC tissues and lymph node metastatic foci in comparison with well-differentiated CRC tissues and moderately differentiated CRC tissues. Functional annotation enrichment analysis indicated that the top 100 genes co-expressed with PPFIA4 were enriched in the G-protein coupled peptide receptor activity, leukotrience B4 receptor activity, and peroxisome proliferator-activated receptors and hypoxia-inducible factor-1 signaling pathways. In addition, miR-485-5p negatively regulates the expression of PPFIA4. Conclusion: PPFIA4 expression is associated with the development of CRCs and may be a novel potential prognostic marker for human CRCs.


Health, stabilization and securitization: towards understanding the drivers of the military role in health interventions.
In the post-Cold War world, health issues have become firmly rooted in state foreign policies through initiatives such as the UK's 'Health is Global' strategy. However, since 9/11, there has also been growing interest in the interactions between health sector interventions and state fragility. Whilst fragility clearly has a negative impact upon both health outcomes and the capacity of the state to respond to health issues generally, there has been a growing assumption amongst policy makers and practitioners alike that carefully formulated health programmes contribute both to social stability and more widely to a state- and peace-building agenda. This process risks being co-opted by the debates on 'stabilization'--a discourse configured around addressing state fragility and often associated with the interventions in Iraq and Afghanistan. Consequently, this article explores the emergence of health interventions as 'strategic tools' linked to the stabilization debate, explores the emergence of the 'health as a bridge for peace' (HBP) debate, assesses some of the evidence available for HBP and finally focuses on the issues arising from the use of militarized health interventions, particularly in Helmand.


Early treatment with AT III in acute liver failure.
In acute liver failure there is often evidence of consumption coagulopathy in addition to interference with the synthesis of coagulation enzymes. Seven patients in hepatic coma (Grade IV-V) were treated by baboon liver perfusion bypass. Replacement therapy with antithrombin III (AT-III) proved useful in the management of the consumption coagulopathy. In the course of further work antithrombin III replacement therapy was given to 13 patients with acute liver failure at an early stage, before they could lapse into deep coma. Six patients with a Colombi index (the sum of Factors II, V and VII) below 75% - an unfavourable prognostic sign - survived the episode of acute liver failure. Early replacement with antithrombin III can be used to treat the coagulation abnormalities which occur during acute liver failure and should gain time for liver cell regeneration to take place.


Malignant transformation of a gangliocytoma/ganglioglioma into a glioblastoma multiforme: a molecular genetic analysis. Case report.
A gangliocytoma/ganglioglioma with no atypical or malignant features was subtotally resected from the right temporal lobe of a 16-year-old woman. A second resection was performed 8 years later to treat a locally recurrent lesion with increased cellularity that was diagnosed as a World Health Organization Grade II ganglioglioma on the basis of neuropathological examination. Molecular analysis of the recurrent tumor revealed a TP53 gene mutation, but no amplification of the epidermal growth factor receptor (EGFR) gene. Radiotherapy (60 Gy) was administered after the second resection. The patient returned 1 year later with a second focal recurrence. The specimen obtained during the third resection of tumor exhibited exclusively astrocytic differentiation, cellular pleomorphism with multinucleated cells, high mitotic activity, and endothelial proliferation. Therefore, the tumor was diagnosed to be a glioblastoma multiforme (GBM). Molecular analysis of tumor DNA from the second recurrent tumor demonstrated the presence of the TP53 mutation, which previously had been observed in the first recurrent tumor, but again no evidence of EGFR amplification. Findings demonstrate that the presence of TP53 mutation in progressed gangliogliomas should be interpreted as a progression-associated mutation rather than a consequence of treatment. This is the first report to indicate that the molecular pathways of gangliocytomas/gangliogliomas progressing to become GBMs may parallel those of diffuse astrocytomas progressing to become GBMs.


[An assessment of the therapeutic efficacy of gene-engineered human alpha 2-interferon in patients with acute viral hepatitis B].
The clinical trials of alpha 2-interferon (alpha 2-IF) (reaferon) in 412 patients with acute viral hepatitis B (AVHB) permitted the establishment of the optimal therapeutic dose and the schedule for the drug use. The drug tolerance appeared satisfactory on the whole. alpha 2-IF was found to have a beneficial effect on the clinical course of VHB. The relationship was established between the therapeutic effectiveness of the drug and the clinical variants of the disease as well as the time of drug administration. The highest clinical effect (in 86.3%) was attained as a result of early (before the 7th day of jaundice) use of alpha 2-IF in patients with the acute-cyclic pattern of VHB. That effect consisted in the reduction of the treatment period (by 6-8 days), in a 2-fold reduction of the incidence of HBs-antigenemia, in rapid stimulation of the IF system, and in the initially low activity of natural killers. If the drug was administered later, the positive clinical effect was detectable only in 61% of the patients. In cholestatic VHB, alpha 2-IF did not produce any therapeutic effect.