Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial.
Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed.


Beçhet's disease: a rare cause of rectovaginal fistula.
A 50-year-old woman with Beçhet's disease presented with episodic diarrhoea and generalised abdominal pain. She was on regular mycophenolate maintenance therapy, being intolerant of both ciclosporin and azathioprine. Previous rectal biopsy was consistent with colitis, probably associated with Beçhet's disease. During this admission, she began passing faecal matter per vaginam. Digital rectal examination confirmed the presence of a large rectovaginal fistula. She underwent urgent laparotomy for a subtotal colectomy with end ileostomy. Although there were no signs of septicaemia preoperatively, small perforations were identified in the caecum and at the splenic flexure on laparotomy. Histopathology confirmed the presence of multiple shallow ulcers throughout the colon with features suggestive of Beçhet's colitis.


The airway epithelium: soldier in the fight against respiratory viruses.
The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.


Evaluation of alkyl polyglucoside as an alternative surfactant in the preparation of peptide-loaded nanoparticles.
The present study was carried out to evaluate potentials of alkyl polyglucoside (APG) as an alternative surfactant/stabilizer in the preparation of peptide-loaded nanoparticles. hGF(2) (human gel filtration fraction 2) was used as a model peptide and APG based on C(10) fatty alcohol (decyl polylglucoside) was used as a representative surfactant. PLA (poly D,L-lactide) and PLGA (poly D,L-lactide-co-glycolide) based nanoparticles were prepared and the effect of APG on particle size, entrapment efficiency and biological activity was evaluated. At a concentration as low as 0.05% w/v, APG provided an excellent stabilization effect, resulting in nanoparticles with better encapsulation efficiency and particle size well below 450 nm. The effective concentration of APG was found to be much less (10-fold) as compared to PVA. Moreover, APG also showed low residual content as compared to PVA. In-vitro and in-vivo biological activity evaluation confirmed that encapsulated peptide was compatible with APG. These preliminary results suggest that APGs can be used as alternate surfactants for nanoparticle preparation.


Early discharge after total thyroidectomy: a retrospective feasibility study.
The continued hospitalization after total thyroidectomy is often due to the onset of hypocalcemic complications more than 24 hours after surgery. So it would be important to predict which patients will not develop the hypocalcemic complication to discharge them early. This was the aim of our study. Our retrospective study was conducted on 327 consecutive thyroidectomized patients, operated on for benign and malignant diseases. We evaluated the values of preoperative serum calcium levels (Cal0) and of the first postoperative day (Cal1) and two new variables were calculated (dCal and dCaln). The same thing was made on a subgroup of 111 patients in whom also parathiroyd hormone (PTH) values were detected. Statistical analysis was performed with the goal of determining if we could establish a safe criterion for discharge at 24 hours after surgery and if there is a correlation between suitability for discharge and diagnosis. As to discharge, the predictive power of the discriminant function applied was significant both on the total of patients and in the subgroup of 111 patients, but it was clinically unacceptable because it would expose us to a 21% to 27% error rate. It is not possible to identify a threshold, below which to consider patients surely dischargeable. The diagnosis does not appear correlated with the suitability for discharge. On the basis of serum calcium and PTH levels in the first postoperative day, it is impossible to predict which patients can be discharged 24 hours after surgery without incurring in hypocalcemic complications.


Morphological and physiological properties of caudal medullary expiratory neurons of the cat.
The activity of respiratory neurons in the caudal part of the nucleus retroambigualis (NRA) was recorded intracellularly in decerebrated, spontaneously breathing cats. Spinal projections of these neurons were determined by antidromic stimulation at the C3 segment. A high concentration of bulbospinal expiratory (BS-E) neurons was identified in the caudal NRA, whereas the inspiratory (I) neurons, not activated antidromically, were also found to be intermingled in the same region. The BS-E neurons had ramp-like depolarizing potentials during expiration, and repolarized rapidly at the onset of phrenic nerve discharge. The I neurons depolarized abruptly in the early I phase, and repolarized gradually thereafter, namely, they were early-I neurons. Intracellular current injections revealed postsynaptic inhibition of the BS-E neurons during inspiration, as evidenced by inhibitory postsynaptic potential reversal. Using the technique of intracellular labeling with horseradish peroxidase, seven well-stained expiratory cells located in the caudal NRA revealed detailed information about axonal morphology: the axon projected rostrally and dorsomedially for the first 2 mm after emerging from the soma, then turned caudally and ventrally along two different courses, and crossed the midline of the medulla almost at the same rostrocaudal level as the soma. No axon collaterals were observed along the length of the stained portion, indicating that the BS-E neurons cannot influence other respiratory neurons in the brainstem. It has been concluded that the NRA expiratory neurons are involved only in spinal action, and that they receive a postsynaptic inhibition during inspiration.(ABSTRACT TRUNCATED AT 250 WORDS)


Premenstrual symptoms and dysmenorrhoea among Muslim women in Zaria, Nigeria.
To document the premenstrual and menstrual symptoms of Muslim women, with a view to providing adequate and sensitive care. Two hundred Muslim women were interviewed at Ahmadu Bello University Teaching Hospital and Muslim Specialist Hospital, both in Zaria between August and October 2003. Premenstrual symptoms were present in 23.8% of the women and breast pain was the commonest symptom (50%). Self-medication was practiced by those who needed medication for the premenstrual symptoms (29.8%). Premenstrual symptoms were significantly associated with lower parity (p = 0.02), previous (p = 0.03) and current (p = 0.01) contraceptive use and dysmenorrhoea (p = < 0.001). Dysmenorrhoea was present in 36.4% and was significantly associated with lower age (p = 0.03), and lower parity (p = 0.01). Health care workers and the general public need to be aware of premenstrual symptoms and dysmenorrhoea in order to provide adequate care and support that is sensitive to Muslim women's needs. Health care providers should also be aware that premenstrual symptoms are more likely to coexist with dysmenorrhoea and provide therapies that can cater for both problems whenever possible.


Fatty acyl-coenzyme A elongation in brain of normal and quaking mice.
Microsomal enzyme systems from mouse brain that catalyze, respectively, the elongation of palmitoyl-coenzyme A (palmitoyl-CoA), stearoyl-CoA, or arachidyl-CoA appear and reach maximal activity at different times after birth of the animal. A specific C(20)-CoA elongating system exists in mouse brain in addition to the previously recognized C(16)-CoA and C(l8)-CoA elongating enzymes. The C(20)-CoA elongation system is severely reduced in the mutant quaking mouse.


A pipeline for RNA-seq data processing and quality assessment.
We present an R based pipeline, ArrayExpressHTS, for pre-processing, expression estimation and data quality assessment of high-throughput sequencing transcriptional profiling (RNA-seq) datasets. The pipeline starts from raw sequence files and produces standard Bioconductor R objects containing gene or transcript measurements for downstream analysis along with web reports for data quality assessment. It may be run locally on a user's own computer or remotely on a distributed R-cloud farm at the European Bioinformatics Institute. It can be used to analyse user's own datasets or public RNA-seq datasets from the ArrayExpress Archive. The R package is available at www.ebi.ac.uk/tools/rcloud with online documentation at www.ebi.ac.uk/Tools/rwiki/, also available as supplementary material.


An international study of public contact with people who have an intellectual disability.
People with intellectual disability (ID) are often socially isolated, and many experience stigma and discrimination. Increased contact with the general public is thought to overcome prejudices. This large-scale international study had three main aims: to determine the type and frequency of contact that the general public has with people with ID; to identify the personal characteristics of those who have greater contact; and to examine the public's level of comfort at the prospect of having contact with people with ID. Self-completed online questionnaires were administered to nationally representative panels of respondents in 17 countries; totally 24 504 persons. Multivariate analyses were used to identify respondents more likely to have had frequent personal contact with persons with ID from those with infrequent or no contact and those respondents who were most comfortable at meeting a person with ID. Internationally around one in four of the general population reports having frequent personal contact with people who have an ID although this varied from 7% in Japan to 46% in Panama. The principal forms of contact were through friendships, neighbours or extended family members. Over all countries, volunteering and engagement with Special Olympics were the two main predictors of frequent personal contact followed by employment in the education, health or social care field, being a parent of children under 18 years, playing sports and being employed. People who reported frequent personal contact were also more comfortable at meeting a person with ID. This international dataset provides a baseline against which public contact can be compared across countries and changes monitored over time. The findings suggest ways in which greater contact can be promoted and making the public more comfortable at meeting people with ID.


Impaired-inactivation of FoxO1 contributes to glucose-mediated increases in serum very low-density lipoprotein.
For patients with diabetes, insulin resistance and hyperglycemia both contribute to increased serum triglyceride in the form of very low-density lipoprotein (VLDL). Our objective was to define the insulin conditions in which hyperglycemia promotes increased serum VLDL in vivo. We performed hyperglycemic-hyperinsulinemic clamp studies and hyperglycemic-hypoinsulinemic clamp studies in rats, with metabolic tracers for glucose flux and de novo fatty acid synthesis. When blood glucose was clamped at hyperglycemia (17 mm) for 2 h under hyperinsulinemic conditions (4 mU/kg . min), serum VLDL levels were not increased compared with baseline. We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1.


Bark consumption by voles in relation to mineral contents.
Recent field experiments with impregnated wooden sticks have demonstrated a pronounced use by small rodents of mineral supplies, especially sodium, and such findings seemed related to vole damage to forestry seedlings. Consumption of the bark of experimentally introduced aspen twigs and of sodium-impregnated sticks by voles (mainly or onlyMicrotus agrestis) correlated significantly on clear-cuts but not on unmanipulated abandoned fields. Such a correlation appeared when abandoned fields were cut continuously in summer. At vole peak densities, bark of pine seedlings experimentally fertilized with sodium was consumed but not bark of seedlings fertilized with calcium or control seedlings. Field pine seedlings attacked by voles had significantly higher levels of calcium, sodium, and phosphorus than the nearest untouched seedling. However, sodium and phosphorus contents correlated strongly. Sodium and calcium supply to voles in laboratory feeding trials did not diminish the moderate interest in pine bark. Such conditions are, however, assumed to mimic a situation of bark sampling in low-density populations. Sodium, and possibly also calcium, requirements are concluded to be partial determinants of the destructive bark consumption by voles at the peaks of their multiannual population cycles.


CT appearance of rheumatoid pericarditis.
In patients with rheumatoid arthritis who develop symptoms of right heart failure, it is important to consider rheumatoid involvement of the pericardium because untreated rheumatoid pericarditis is often fatal. In addition to echocardiography and right heart catheterization, computed tomography affords a method of detecting pericardial effusion or a markedly thickened pericardium.


Preliminary Evidence for a Compromised T-Cell Compartment in Maltreated Children with Depression and Posttraumatic Stress Disorder.
Adverse childhood experiences, such as maltreatment, and affective disorders are associated with a proinflammatory state and/or variably compromised counts in lymphocyte subsets in adults. Animal models of social stress indicate that recent thymic emigrant cells (RTE), which maintain the T-cell compartment, are affected. In this study, we examined the association between lymphocyte subsets, and depression and posttraumatic stress disorder (PTSD) among 16 maltreated children (aged 6-17 years) 1-3 years after the intervention by the Child Protection Team and among 14 healthy age-matched controls. The participants completed psychological assessment and had blood drawn for fluorescent-activated cell sorting analysis. Among maltreated children and adolescents, depression was associated with lower counts of RTEs and T-helper cells after controlling for age. We found additional trends and large effect sizes with regard to the percentages of these cells, as well as for related lymphocyte subsets. Similar effects were found for PTSD, i.e. lower counts of naïve T cells, which was also supported by a trend for their percentage. Compared to controls, maltreated participants with a clinical level of depression had decreased percentages of RTEs, with a similar trend for PTSD. Limited by the nature of a pilot study and the small sample size, these preliminary findings of a compromised T-cell compartment related to psychiatric symptoms in maltreated children and adolescents need to be further studied; particularly the role of RTEs needs further evaluation.


Translation of intronless RNAs is strongly stimulated by the Epstein-Barr virus mRNA export factor EB2.
The Epstein-Barr virus protein (EB2) allows the nuclear export of a particular subset of early and late viral RNAs derived from intronless genes. EB2 is conserved among most herpesvirus members and its presence is essential for the production of infectious particles. Here we show that, besides its role as a nuclear export factor, EB2 strongly stimulates translation of unspliced mRNAs without affecting overall cellular translation. Interestingly, this effect can be reversed by the addition of an intron within the gene. The spliced mRNA is then efficiently exported and translated even in the absence of EB2. Moreover, we show that EB2 associates with translating ribosomes and increases the proportion of its target RNA in the polyribosomal fraction. Finally, testing of EB2 homolog proteins derived from EBV-related herpesviruses, shows that, even if they play similar roles within the replication cycle of their respective virus, their mechanisms of action are different.


Retrocaecal appendix position--findings during the clasic appendectomy.
Appendicitis is one of the most common diseases that require urgent surgical intervention. Due to its position, the inflamed appendix can cause many complications in abdominal cavity. Most of these complications are based on the anatomical position of the appendix. According to world literature over 65% of the anatomical positions of appendix is retrocaecal position, followed paracaecal and then the other positions of the appendix in different percentages. The main goal of this research is to shown that anatomical retrocaecal position of the appendix can lead to prolonged hospitalization and more often occurrence of appendicitis complications. The research is based on patients who had appendectomy during 2009 at the Cantonal Hospital Zenica and General Hospital Tesanj. The study included approximately 400 respondents and the method of research was of retrospective, descriptive and analytical type. According to the results of this research we can conclude that in our country is not devoted enough attention to the anatomic position of the appendix and that we are not using enough diagnostic methods such as ultrasound and CT in determining the anatomic position to help determine the course of the disease. Retrocaecal appendix position according to the obtained data from this study did not cause many complications in classical appendectomy but this can be attributed to insufficient observation of the anatomical position of the appendix.


Role of titanium dioxide nanoparticles in the elevated uptake and retention of cadmium and zinc in Daphnia magna.
Titanium dioxide nanoparticles (nano-TiO(2)) are now widely applied in consumer products, and the dispersion of nano-TiO(2) may adsorb metals and modify their behavior and bioavailability in the aquatic environment. In the present study, the aqueous uptake, dietary assimilation efficiency (AE), and efflux rate constant (k(e)) of two toxic metals (cadmium-Cd, and zinc-Zn) adsorbed on nano-TiO(2) in a freshwater zooplankton Daphnia magna were quantified. The biokinetics was then compared to daphnids that were exposed only to dissolved metals as controls. The aqueous uptake of Cd and Zn involved an initial rapid uptake and then an apparent saturation, and the uptake of metals was accompanied by an ingestion of nano-TiO(2). The AEs of Cd and Zn adsorbed on nano-TiO(2) were 24.6 ± 2.4-44.5 ± 3.7% and 30.4 ± 3.4-51.8 ± 5.0%, respectively, and decreased with increasing concentrations of nano-TiO(2). Furthermore, the difference between the AEs of Cd and Zn indicated that the desorption of Cd and Zn from nano-TiO(2) may have occurred within the gut of daphnids. With the use of algae as carrier, the AEs of Cd and Zn adsorbed on nano-TiO(2) were significantly higher than those of Cd and Zn directly from nano-TiO(2). The efflux rate constants of Cd and Zn adsorbed on nano-TiO(2) in the zooplankton were significantly lower than those of Cd and Zn not adsorbed on nano-TiO(2). Our study shows that the uptake and retention of toxic metals is enhanced when they are adsorbed on nano-TiO(2), and suggests more attention be paid to the potential influences of nano-TiO(2) on the bioavailability and toxicity of other contaminants.


Trajectory of Improvement in Myelopathic Symptoms From 3 to 12 Months Following Surgery for Degenerative Cervical Myelopathy.
Degenerative cervical myelopathy (DCM) is a progressive disease resulting from cervical cord compression. The modified Japanese Orthopaedic Association (mJOA) is commonly used to grade myelopathic symptoms, but its persistent postoperative improvement has not been previously explored. To utilize the Quality Outcomes Database (QOD) to evaluate the trajectory of outcomes in those operatively treated for DCM. This study is a retrospective analysis of prospectively collected data. The QOD was queried for patients undergoing elective surgery for DCM. Patients were divided into mild (≥14), moderate (9-13), or severe (<9) categories for their baseline severity of myelopathic symptoms (mJOA scores). A parsimonious multivariable logistic regression model was fitted with 2 points improvement on mJOA from 3- to 12-mo follow-up as the outcome of interest. A total of 2156 patients who underwent elective surgery for DCM and had complete 3- and 12-mo follow-up were included in our analysis. Patients improved significantly from baseline to 3-mo on their mJOA scores, regardless of their baseline mJOA severity. After adjusting for the relevant preoperative characteristics, the baseline mJOA categories had significant impact on outcome of whether a patient keeps improving in mJOA score from 3 to 12 mo postsurgery. Patient with severe mJOA score at baseline had a higher likelihood of improvement in their myelopathic symptoms, compared to patients with mild mJOA score in. Most patients achieve improvement on a shorter follow-up; however, patients with severe symptoms keep on improving until after a longer follow-up. Preoperative identification of such patients helps the clinician settling realistic expectations for each follow-up timepoint.


The effects of lipids and surfactants on TLR5-proteoliposome functionality for flagellin detection using surface plasmon resonance biosensing.
The use of proteoliposomes as affinity elements in conjunction with a surface plasmon resonance sensor is a high-sensitivity alternative for the detection of multiple analytes. However, one of the most important aspects of these conformations is maintaining the functionality of the immobilized protein, which is determined by the choice of lipids and surfactants employed in the reconstitutions. Previously, we demonstrated the functionality of TLR5-proteoliposomes as screening affinity elements of bacterial flagellin. In this new study we change the conditions of immobilization of TLR5 and evaluate how the fluidity of the membrane and the final size of the liposomes affect the functionality of the construct and thus increase their utility as an affinity element for design of new biosensors. In particular, we used reconstructions into preformed liposomes composed of the lipids POPC, POPC-DMPC and POPC-POPE mediated by the use of surfactants OG, Triton X100, and DDM, respectively. The affinity results were evaluated by SPR technology proteoliposomes and were correlated with the anisotropic change in the membrane status; the final sizes of the proteoliposomes were estimated. Our results clearly show the dependence of fluidity and final size of the proteoliposomes with surface plasmon resonance affinity measurements.


Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.
Optic nerve assessment is important for many blinding diseases, with cup-to-disc ratio (CDR) assessments commonly used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, we performed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P=6.2x10(-10), near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a meta-analysis of the combined data yielding P=3.4x10(-10). Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P=1.3x10(-10) to 4.3x10(-11), top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P=1.5x10(-7), in the gene RFTN1. Direct sequencing of ATOH7 in 12 patients with optic nerve hypoplasia, one of the leading causes of blindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher's exact P=0.0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls.


Directed placement of gold nanorods using a removable template for guided assembly.
We have used a temperature sensitive polymer film as a removable template to position, and align, gold nanorods onto an underlying target substrate. Shape-matching guiding structures for the assembly of nanorods of size 80 nm × 25 nm have been written by thermal scanning probe lithography. The nanorods were assembled into the guiding structures, which determine both the position and the orientation of single nanorods, by means of capillary interactions. Following particle assembly, the polymer was removed cleanly by thermal decomposition and the nanorods are transferred to the underlying substrate. We have thus demonstrated both the placement and orientation of nanorods with an overall positioning accuracy of ≈10 nm onto an unstructured target substrate.


A Novel Arg120Pro Mutation in the RP2 Gene in an Iranian Family with X-linked Retinitis Pigmentosa: A Case Report.
As the most common type of inherited retinal degenerative disease, retinitis pigmentosa (RP) has taken clinical and prenatal attention. Considering the clinical importance of consanguineous marriages, new mutations in this type of pregnancy have a high risk and increase the importance of Prenatal Diagnosis (PND). In vitro analysis was done through Whole Exome Sequencing (WES) for a 36-year-old woman who was referred to a genetic laboratory in Kermanshah in 2021 for PND. The woman had consanguineous marriage and was pregnant with twins (a boy and a girl). Mutation confirmation tests were also performed on her husband and both fetuses to find mutations. Moreover, in silico analyses were performed by SWISS-MODEL, ProSA, Molprobity, Swiss-Pdb Viewer, and ERRAT. The WES analysis showed a novel mutation of the RP2 gene (exon2:c. 359G>C: p.R120P) in the 36-year-old pregnant woman. Mutations identified in her husband and her twins revealed changes in protein conformations. Further modeling and validation evaluations showed the replacement of Arg by Pro at the 120th residue site of the cognate protein. For the first time, our report introduced a novel missense mutation in the RP2 gene associated with severe signs of RP in an Iranian family based on an X-linked recessive pattern of genetic inheritance. These findings may pave the way for a better diagnosis of RP in genetic counseling and PND.


Reformulations of practice: beyond experience in paramedic airway management.
"Deliberate practice" and "feedback" are necessary for the development of expertise. We explored clinical performance in settings where these features are inconsistent or limited, hypothesizing that even in algorithmic domains of practice, clinical performance reformulates in ways that may threaten patient safety, and that experience fails to predict performance. Paramedics participated in two recorded simulation sessions involving airway management, which were analyzed three ways: first, we identified variations in "decision paths" by coding the actions of the participants according to an airway management algorithm. Second, we identified cognitive schemas driving behavior using qualitative descriptive analysis. Third, clinical performances were evaluated using a global rating scale, checklist, and time to achieve ventilation; the relationship between experience and these metrics was assessed using Pearson's correlation. Thirty participants completed a total of 59 simulations. Mean experience was 7.2 (SD=5.8) years. We observed highly variable practice patterns and identified idiosyncratic decision paths and schemas governing practice. We revealed problematic performance deficiencies related to situation awareness, decision making, and procedural skills. There was no association between experience and clinical performance (Scenario 1: r=0.13, p=0.47; Scenario 2: r=-0.10, p=0.58), or the number of errors (Scenario 1: r=.10, p=0.57; Scenario 2: r=0.25, p=0.17) or the time to achieve ventilation (Scenario 1: r=0.53, p=0.78; Scenario 2: r=0.27, p=0.15). Clinical performance was highly variable when approaching an algorithmic problem, and procedural and cognitive errors were not attenuated by provider experience. These findings suggest reformulations of practice emerge in settings where feedback and deliberate practice are limited.


Clinical features of large granular lymphocyte leukemia.
The spectrum of large granular lymphocyte (LGL) proliferations consists of four distinct entities: reactive/transient LGL expansion, chronic LGL lymphocytosis, classical indolent LGL leukemia, and aggressive LGL leukemia. LGL leukemias are classified as lymphoid malignancies. They are divided into CD3(+)/T-cell LGL (85% of cases) and CD3(-)/natural killer (NK) cell LGL leukemia (15% of cases). Recent progress in the comprehension of the leukemogenesis has shown a dysregulation of survival signals in leukemic cells. Identification of LGL expansion has been improved using T-cell receptor (TCR)beta/gamma polymerase chain reaction (PCR) analysis and a combination of Vbeta and killer cell immunoglobulin-like receptor (KIR)-specific monoclonal antibodies. LGL leukemias are characterized by a clonal LGL infiltration of the bone marrow, spleen, and liver. Monoclonality is recognized by phenotypic, molecular, and karyotypic analysis. T-LGL leukemias affect the elderly and display a relatively indolent behavior. Approximately 60% to 70% of patients are symptomatic: recurrent infections secondary to chronic neutropenia, anemia, and autoimmune disease such as rheumatoid arthritis are the main clinical manifestations. Long-lasting remission can be obtained with low-dose methotrexate, cyclosporine A, or cyclophosphamide. Conversely, NK LGL leukemias behave aggressively, and most patients do not respond to chemotherapy.


Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era.
Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies. Real-world data with large patient cohorts is currently lacking. Using the nation-wide, population based Belgian Cancer Registry (BCR), all known histological reports of patients diagnosed with an adult-type diffuse glioma in Belgium between 2017 and 2019 were reviewed. The ICD-O-3 morphology codes were matched with the histological diagnosis. The gathered data was transformed into the 2021 WHO classification of CNS tumors using the IDH- and 1p/19q-mutation status. Between 2017 and 2019, 2233 diffuse adult-type gliomas were diagnosed in Belgium. Full molecular status was available in 67,1% of identified cases. The age-standardized incidence rate of diffuse adult-type glioma in Belgium was estimated 8,55 per 100.000 person years and 6,72 per 100.000 person years for grade 4 lesions. Median overall survival time in IDH-wildtype glioblastoma was 9,3 months, significantly shorter compared to grade 4 IDH-mutant astrocytoma (median survival time: 25,9 months). The 3-year survival probability was 86,0% and 75,7% for grade 2 and 3 IDH-mutated astrocytoma. IDH-wildtype astrocytoma has a worse prognosis with a 3-year survival probability of 31,6% for grade 2 and 5,7% for grade 3 lesions. This registry-based study presents a large cohort of adult-type diffuse glioma with known molecular status and uses real-world survival data. It adds to the current literature which is mainly based on historical landmark trials and smaller retrospective cohort studies.


[Microwave emission from water in bioanalytical systems].
Mechanical stimulation of aqueous protein solution was found to be accompanied by electromagnetic radiation in the superhigh frequency range. This radiation was observed at solution temperatures near the phase transitions of water. This effect may occur in various bioanalytical systems, associated with injection of aqueous solutions in these systems, and may have impact on the results of bioalytical measurements. The discovered effect of generation of nonequilibrium microwave emission of water medium (which is the main component of the organism) in the 38-39°C temperature range, i.e. in the range of elevated temperature of the organism (which accompanies pathological condition in humans upon inflammatory diseases, i.e., infactious etc.) may be used for development of new non-invasive methods of disease diagnostics.


Barrett's esophagus: a review of the literature.
Barrett's esophagus (BE) is the premalignant lesion of esophageal adenocarcinoma (EAC) defined as specialized intestinal metaplasia of the tubular esophagus that results from chronic gastroesophageal reflux. Which patients are at risk of having BE and which are at further risk of developing EAC has yet to be fully established. Many aspects of the management of BE have changed considerably in the past 5 years alone. The aim of this review is to define the critical elements necessary to effectively manage individuals with BE. The general prevalence of BE is estimated at 1.6-3% and follows a demographic distribution similar to EAC. Both short-segment (<3 cm) and long-segment (≥3 cm) BE confer a significant risk for EAC that is increased by the development of dysplasia. The treatment for flat high-grade dysplasia is endoscopic radiofrequency ablation therapy. The benefits of ablation for non-dysplastic BE and BE with low-grade dysplasia have yet to be validated. By understanding the intricacies of the development, screening, surveillance, and treatment of BE, new insights will be gained into the prevention and early detection of EAC that may ultimately lead to a reduction in morbidity and mortality in this patient population.


Antitumor Effect of Pyrogallol via miR-134 Mediated S Phase Arrest and Inhibition of PI3K/AKT/Skp2/cMyc Signaling in Hepatocellular Carcinoma.
Though Pyrogallol, one of the natural polyphenols, was known to have anti-inflammatory and antitumor effects in breast and colon cancers, the underlying antitumor mechanisms of Pyrogallol, still remain unclear so far. Here, the antitumor mechanisms of Pyrogallol were elucidated in Hep3B and Huh7 hepatocellular carcinoma cells (HCCs). Pyrogallol showed significant cytotoxicity and reduced the number of colonies in Hep3B and Huh7 cells. Interestingly, Pyrogallol induced S-phase arrest and attenuated the protein expression of CyclinD1, Cyclin E, Cyclin A, c-Myc, S-phase kinase-associated protein 2 (Skp2), p-AKT, PI3K, increased the protein expression of p27, and also reduced the fluorescent expression of Cyclin E in Hep3B and Huh7 cells. Furthermore, Pyrogallol disturbed the interaction between Skp2, p27, and c-Myc in Huh7 cells. Notably, Pyrogallol upregulated miRNA levels of miR-134, and conversely, miR-134 inhibition rescued the decreased expression levels of c-Myc, Cyclin E, and Cyclin D1 and increased the expression of p27 by Pyrogallol in Huh7 cells. Taken together, our findings provide insight that Pyrogallol exerts antitumor effects in HCCs via miR-134 activation-mediated S-phase arrest and inhibition of PI3K/AKT/Skp2/cMyc signaling as a potent anticancer candidate.


BrainScope: interactive visual exploration of the spatial and temporal human brain transcriptome.
Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: a web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human brain transcriptome. Through a novel methodology to explore high-dimensional data (dual t-SNE), BrainScope enables the linked, all-in-one visualization of genes and samples across the whole brain and genome, and across developmental stages. We show that densities in t-SNE scatter plots of the spatial samples coincide with anatomical regions, and that densities in t-SNE scatter plots of the genes represent gene co-expression modules that are significantly enriched for biological functions. We also show that the topography of the gene t-SNE maps reflect brain region-specific gene functions, enabling hypothesis and data driven research. We demonstrate the discovery potential of BrainScope through three examples: (i) analysis of cell type specific gene sets, (ii) analysis of a set of stable gene co-expression modules across the adult human donors and (iii) analysis of the evolution of co-expression of oligodendrocyte specific genes over developmental stages. BrainScope is publicly accessible at www.brainscope.nl.


Increased atrial natriuretic peptide (6-33) binding sites in the subfornical organ of water deprived and Brattleboro rats.
Binding sites for rat atrial natriuretic peptide (6-33) (ANP) were quantitated in the subfornical organ of chronically dehydrated homozygous Brattleboro rats unable to synthesize vasopressin; heterozygous Brattleboro rats, their controls, Long Evans rats and Long Evans rats after 4 days of water deprivation. Brain sections were incubated in the presence of 125I-ANP and the results analyzed by autoradiography coupled to computerized microdensitometry and comparison to 125I-standards. Brattleboro rats and water deprived Long Evans rats presented a higher number of ANP binding sites than their normally hydrated controls. Our results suggest a role of ANP binding sites in the subfornical organ in the central regulation of fluid balance and vasopressin secretion.


Osteosclerosis owing to Notch gain of function is solely Rbpj-dependent.
Osteosclerosis is a pathologic bone disease characterized by an increase in bone formation over bone resorption. Genetic factors that contribute to the pathogenesis of this disease are poorly understood. Dysregulation or mutation in many components of the Notch signaling pathway results in a wide range of human developmental disorders and cancers, including bone diseases. Our previous study found that activation of the Notch signaling in osteoblasts promotes cell proliferation and inhibits differentiation, leading to an osteosclerotic phenotype in transgenic mice. In this study we report a longer-lived mouse model that also develops osteosclerosis and a genetic manipulation that completely rescues the phenotype. Conditionally cre-activated expression of Notch1 intracellular domain (NICD) in vivo exclusively in committed osteoblasts caused massive osteosclerosis with growth retardation and abnormal vertebrae. Importantly, selective deletion of a Notch nuclear effector--Rbpj--in osteoblasts completely suppressed the osteosclerotic and growth-retardation phenotypes. Furthermore, cellular and molecular analyses of bones from the rescued mice confirmed that NICD-dependent molecular alterations in osteoblasts were completely reversed by removal of the Rbpj pathway. Together, our observations show that the osteosclerosis owing to activation of Notch signaling in osteoblasts is canonical in nature because it depends solely on Rbpj signaling. As such, it identifies Rbpj as a specific target for manipulating Notch signaling in a cell-autonomous fashion in osteoblasts in bone diseases where Notch may be dysregulated.


[The sperm swelling test--a new andrologic method].
104 semen specimen from 15 donors of the AID-program with proven fertility were investigated and the hypoosmotic swelling test -HOS-test (Jeyendran et. al.) was carried out. The results of this test had been compared with the sperm motility and the sperm motile efficiency (Ishii et. al.). All donors showed a high rate of test-positive sperms for these three methods. The HOS-test had a lower scattering and a higher individual specificity than the other methods.


Quality of life in children with end-stage renal disease based on a PedsQL ESRD module.
Health-related quality of life (HRQOL) is an essential subject for children with end-stage renal disease (ESRD) and their families. We performed a cross-sectional investigation of HRQOL in children undergoing renal replacement therapies, such as dialysis and renal transplantation, using the 34-item Pediatric Quality of Life Inventory 3.0 End-Stage Renal Disease (PedsQL 3.0 ESRD) module. We assessed 92 ESRD patients aged 2-18 from four Korean university hospitals. The male:female ratio was 44:48, and the most common cause of ESRD was chronic glomerulonephritis. Fifty-five children were treated by dialysis, and 37 received renal transplantation. Transplant patients had better HRQOL than dialysis patients in two domains in parent proxy reports: "About my kidney disease" and "Worry." In child self-reports, transplant patients had better HRQOL than dialysis patients in one domain: Treatment problems. However, there were no significant differences in total QOL scores between peritoneal dialysis (PD) and transplant patients in child self-reports. In addition, there were differences in the ESRD module scores between child self- and parent proxy reports. Children usually reported better QOL than their parents. Child self-reports showed significantly higher QOL scores than parent proxy reports in the domains of General fatigue, Family & peer interaction, and Worry. Children on PD self-reported a significantly higher QOL than children on hemodialysis (HD). The PedsQL 3.0 ESRD module may be useful as an ESRD-specific instrument to evaluate HRQOL in children; however, a larger, longitudinal prospective study is warranted.


Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins.
The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes proteins required for RNA transcription and genome replication as large polyproteins that are proteolytically processed by virus-encoded proteinases to produce mature replicase proteins. In this report, we generated antibodies against SARS-CoV predicted replicase protein and used the antibodies to identify and characterize 12 of the 16 predicted mature replicase proteins (nsp1, nsp2, nsp3, nsp4, nsp5, nsp8, nsp9, nsp12, nsp13, nsp14, nsp15, and nsp16) in SARS-CoV-infected Vero cells. Immunoblot analysis of infected-cell lysates identified proteins of the predicted sizes. Immunofluorescence microscopy detected similar patterns of punctate perinuclear and distributed cytoplasmic foci with all replicase antibodies and as early as 6 h postinfection. Dual-labeling studies demonstrated colocalization of replicase protein nsp8 with nsp2 and nsp3 in cytoplasmic complexes and also with LC3, a protein marker for autophagic vacuoles. Antibodies directed against mouse hepatitis virus (MHV) virions and against the putative RNA-dependent RNA polymerase (Pol) detected SARS-CoV nucleocapsid and nsp12 (Pol), respectively, in SARS-CoV-infected Vero cells. These results confirm the predicted protein processing pattern for mature SARS-CoV replicase proteins, demonstrate localization of replicase proteins to cytoplasmic complexes containing markers for autophagosome membranes, and suggest conservation of protein epitopes in the replicase and nucleocapsid of SARS-CoV and the group II coronavirus, MHV. Further, the results demonstrate the ability of replicase antibodies to detect SARS-CoV-infected cells as early as 6 h postinfection and thus represent important tools for studies of SARS-CoV replication, inhibition, and diagnosis.


Publication bias in antipsychotic trials: an analysis of efficacy comparing the published literature to the US Food and Drug Administration database.
Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. FDA Drug Approval Packages for eight second-generation antipsychotics-aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone--were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant. The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs.


Reconstruction of Large Perineal and Pelvic Wounds Using Gracilis Muscle Flaps.
The reconstruction of large defects after abdominoperineal resections and pelvic exenterations has traditionally been accomplished with vertical rectus myocutaneous flaps (VRAMs). For patients requiring two ostomies, robot-assisted abdominoperineal resections (APRs), and to avoid the morbidity of a VRAM harvest, the authors have used the gracilis muscle flap to reconstruct the large dead space in these patients. A retrospective analysis of 16 consecutive APRs (10 with concomitant pelvic exenterations) reconstructed with gracilis flaps during a 2-year period was performed. Gracilis muscle flaps were used to obliterate the dead space after primary skin closure was ensured with adduction of the legs. All 16 patients had locally advanced cancers and had received neoadjuvant chemotherapy and radiation. Of these 16 patients, 10 had pelvic exenterations. All the patients had reconstruction with gracilis flaps (6 bilateral flaps). One major wound complication in the perineum occurred as a result of an anastomotic leak in the pelvis, but this was managed with conservative dressing changes. Three patients had skin separation in the perineum greater than 5 mm with intact subcutaneous closure. No patients required operative debridement or revision of their perineal reconstruction. No perineal hernias or gross dehiscence of the skin closure occurred. Large pelvic and perineal reconstructions can be safely accomplished with gracilis muscle flaps and should be considered as an alternative to abdominal-based flaps.


The beta-adrenergic receptor: rapid purification and covalent labeling by photoaffinity crosslinking.
New procedures for the rapid purification and covalent labeling of the beta-adrenergic receptors have been developed that should greatly accelerate progress in the study of these widely distributed adenylate cyclase-coupled receptors. Chromatography of solubilized receptor preparations on a Sepharose-alprenolol affinity gel followed by HPLC on steric exclusion columns lead to rapid (2 days) and high yield (approximately 30%) purification of the receptors from frog erythrocytes. The receptor obtained by these rapid procedures appears to be composed entirely of 58,000 Mr subunit(s) and to be identical to that previously purified by much lengthier procedures [Shorr, R. G. L., Lefkowitz, R. J. & Caron, M. G. (1981) J. Biol. Chem. 256, 5820-5826]. A novel, very high affinity, specific beta-adrenergic antagonist, p-aminobenzylcarazolol, has also been synthesized. It can be radioiodinated to theoretical specific radioactivity with 125I (2,200 Ci/mmol). This radioligand, which possesses an arylamine moiety, may then be covalently incorporated into the receptor binding subunit (58,000 Mr peptide) of the frog erythrocyte membranes by the use of the bifunctional photoactive crosslinker N-succinimidyl-6-(4'-azido-2'- nitrophenylamino)hexanoate (SANAH). Covalent incorporation is blocked by various drugs with a strict beta-adrenergic specificity. This suggests that the photoaffinity crosslinking approach may be useful for labeling a variety of small molecule and neurotransmitter receptors when appropriate ligands can be synthesized.


Herpes Virus Encephalitis in Adults: Current Knowledge and Old Myths.
Herpes simplex virus (HSV) encephalitis is uncommon in clinical practice, but is frequently suspected in patients with acute alterations of consciousness. Symptoms and physical signs are nonspecific, and diagnostic confirmation typically hinges on demonstration of viral DNA in cerebrospinal fluid. Brain MRI is helpful in diagnosis and provides prognostic information. Early initiation of intravenous acyclovir is essential to optimize the patient's chances of favorable recovery. HSV encephalitis can trigger an autoimmune reaction with the possible appearance of antibodies to neuronal surface antigens. Thus, recrudescence of neurologic impairment after a treated episode of HSV encephalitis warrants consideration of secondary autoimmune encephalitis.


Am I going to die now? Experiences of hospitalisation and subsequent life after being diagnosed with aortic dissection.
Aortic dissection is a life-threatening condition with mortality up to 75%. In the acute phase, patients are constrained with total bed rest until pain relief and blood pressure has been stabilised. Some need surgery. Aortic dissection is associated with anxiety and poor health-related quality of life. However, no study has explored the experience of living through aortic dissection. The aim of this study was to explore the patient experience of living through aortic dissection. Data were collected in interviews with 10 patients who lived through aortic dissection. Data were gathered and analysed using a phenomenological approach. The qualitative analysis revealed four themes; 'Am I going to die now? - the existential turning point when diagnosed with life-threatening aortic dissection', 'compromised integrity during admission - experiences of hospitalisation', 'Signals from my body - a new awareness of the body after discharge', 'What can I do? - uncertainties about physical activity in daily life posthospitalisation'. Experiences of aortic dissection are a life-threatening and overwhelming existential life situation which includes a period of constraining hospitalisation and experiences a compromised integrity. Patients have substantial concerns regarding body signals and a constantly uncertainty about what kind of activity level they can sustain which affect their mental well-being and their daily life. These findings contribute to understanding and elaborating a more nuanced description of being diagnosed with aortic dissection, which is essential when planning high-quality treatment and care, developing sufficient follow-up and preventing adverse events.


A review of toxicology studies on cyanurate and its chlorinated derivatives.
Chlorinated cyanurates are added to swimming pools as disinfectants. In the presence of water, these materials hydrolyze to yield cyanurate and hypochlorous acid. To evaluate the safety of exposure to these materials, a comprehensive testing program was undertaken. This review summarizes the results of acute and subchronic tests on chlorinated isocyanurates. Findings from acute, subchronic, reproduction, metabolism, mutagenicity, and chronic/carcinogenicity tests on cyanurate are also summarized. Results from these tests indicate that chlorinated isocyanurates are safe for use in swimming pools.


[Psychological aspects of severe burn injuries in childhood and adolescence].
Severe burn injuries are the most painful injuries known, and treatment procedures can be extremely aversive as well. Pediatric burn suvivors must often live with permanent disfigurement und physical disabilities. This article presents a review of psychological aspects of severe burn injuries in children and adolescents. The review is based on the scientific literature and own professional experiences. After discussing predisposing factors of burn injuries three phases of medical therapy are defined: 1) acute phase, 2) phase of surgical therapy and 3) phase of rehabilitation. For each of these stages common psychological reactions and potential psychological interventions are presented. Finally psychosocial sequelae and longterm adjustment of pediatric burn injuries are described and implications for the psychological treatment of burned children and adolescents are discussed.


Heterologous expression of mitochondria-targeted microbial nitrilase enzymes increases cyanide tolerance in Arabidopsis.
Anthropogenic activities have resulted in cyanide (CN) contamination of both soil and water in many areas of the globe. While plants possess a detoxification pathway that serves to degrade endogenously generated CN, this system is readily overwhelmed, limiting the use of plants in bioremediation. Genetic engineering of additional CN degradation pathways in plants is one potential strategy to increase their tolerance to CN. Here we show that heterologous expression of microbial nitrilase enzymes targeted to the mitochondria increases CN tolerance in Arabidopsis. Root length in seedlings expressing either a CN dihydratase from Bacillus pumilis or a CN hydratase from Neurospora crassa was increased by 45% relative in wild-type plants in the presence of 50 μm KCN. We also demonstrate that in contrast to its strong inhibitory effects on seedling establishment, seed germination of the Col-0 ecotype of Arabidopsis is unaffected by CN.


Reinforced stapling does not reduce postoperative pancreatic fistula in distal pancreatectomy: a systematic review and meta-analysis.
Postoperative pancreatic fistula (POPF) is a severe complication after distal pancreatectomy (DP); however, it is unclear how to effectively reduce the incidence. The purpose of this meta-analysis is to determine whether reinforced stapling reduces POPF after DP. From February 2007 to April 2023, a comprehensive search of electronic data and references was conducted in PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. In this study, the perioperative outcomes were evaluated for the reinforced stapler (RS) group and the standard stapler (SS) group in DP using Review Manager Software. Using fixed- or random-effects models, pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. In total, three randomized clinical trials (RCTs) with 425 patients and five observational clinical studies (OCS) with 318 patients were included. In pooled meta-analyses from RCTs, there was no difference between the two groups in the incidence of POPF (OR = 0.79; 95% CI [0.47,1.35]; P = 0.39), intraoperative blood loss (MD = 10.66; 95% CI [- 28.83,50.16]; P = 0.6), operative time (MD = 9.88; 95% CI [- 8.92,28.67]; P = 0.3), major morbidity (OR = 1.12; 95% CI [0.67,1.90]; P = 0.66), reoperation (OR = 0.97; 95% CI [0.41,2.32]; P = 0.95), readmission (OR = 0.99; 95% CI [0.57,1.72]; P = 0.97) or hospital stay (MD = - 0.95; 95% CI [- 5.22,3.31]; P = 0.66). However, the results of POPF and readmission were favorable for RS in the OCS group.


Preserving alveolar bone growth following cervical root fracture: a case report.
Root fracture injuries affect 0.5%-7% of permanent teeth. Although cervical root fractures are less frequent in children, their serious consequences and poor prognosis may lead to tooth loss. In this case presentation, we discuss a treatment approach chosen to preserve alveolar bone growth following a cervical root fracture in an 8-Year-old boy.


[Vulnerability to depression in children and adolescents: update and perspectives].
Depression in children and adolescents is associated with poor psychosocial functioning, high psychiatric comorbidity, risk of recurrent episodes or onset of bipolar disorder. These findings emphasize the importance of early identification of children and adolescents having elevated risk for future depression and further development, evaluation and greater availability of prevention strategies. Our review aims an update about depressive vulnerability in children and adolescents in the perspective of better identification of at-risk populations and targeting of prevention programs. Psychopathology, in particular anxiety and disruptive disorders are well identified risk-factors for later depression. Subclinical depressive symptomatology, also termed "demoralization", also identifies high-risk populations, likely to become incident cases of depression. It is still unclear whether this condition is prodromal depression, a specific clinical entity or the expression of biological and/or cognitive vulnerability. Familial risk for depressive disorders involves both genetic and psychosocial factors. Marital discord, poor communication and dysfunctional parenting practices are often present in families with affective disorders and can be implicated in increased depressive vulnerability in the offspring. Research on individual vulnerability in children and adolescents has focused on temperamental and cognitive characteristics. Temperament traits describe individual differences in reactivity and behavior. High emotionality, defined as the tendency to become upset easily and intensely has been associated with an increased risk for subsequent major depression. However, as the majority of high scorers will not become depressive cases, emotionality should not be the only criterion for selection of at-risk populations. Cognitive style including poor self esteem, low social competence and negative attributions are also associated with increased likelihood of depressive symptoms, but their predictive value for the onset of clinical depressive episodes needs further investigation. Familial and individual vulnerability is likely to heighten the depressogenic impact of life events and psycho-social adversity. Prevention interventions have been developed in the United States for children and adolescents at-risk for depression. In France, clinicians witness growing demands from families with affective illness concerned with risk of parent-child transmission of depressive vulnerability, prevention and early identification of symptoms. To meet this kind of emerging needs and to prevent family dysfunction, a preventive program targets offspring of depressed parents and uses clinician-based family approaches. Family and individual sessions aim a better understanding of illness experience and encourage the parents to identify and foster resilience in their children. Another type of preventive intervention focuses on children and adolescents with subclinical depressive symptoms, eventually associated with behavioral problems ou high level of parental conflict, recruited in school settings. These school-based interventions combine cognitive and social problem-solving techniques. Both familial and school-based preventive interventions have proven applicable and promising in high-risk children and adolescents. Perspectives are more systematic identification of risk groups, including youngsters with past or current non affective symptoms who might benefit from depression prevention, long-term evaluation and cross-cultural applications of prevention programs.


Correlates of long sleep duration.
Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality. Whether this association is causal and what pathways explain this association are unknown. We sought to identify factors that could potentially explain the association between long sleep and mortality. Cross-sectional epidemiologic survey. Middle-aged women (n = 60,028) participating in the Nurses Health Study II who reported a habitual sleep duration of 7 hours or more. Multiple sclerosis (odds ratio [OR] = 3.7, 95% confidence interval [3.0-4.5]), antidepressant use (OR = 3.1, [2.9-3.3]), benzodiazepine use (OR = 3.0 [2.6-3.3]), and systemic lupus erythematosus (OR = 2.9, [2.3-3.6]) were the factors most strongly associated with prolonged sleep. Combining these data with prevalence information and a range of plausible associations with mortality, the confounding rate ratio was estimated. This parameter is the ratio of the unadjusted long sleep-mortality rate ratio to the rate ratio adjusted for the factor and measures the extent that the factor can alter the long sleep-mortality association, either through confounding or as a causal intermediate. Based on this parameter, psychiatric and socioeconomic factors have the greatest potential to influence the long sleep-mortality relationship. Assuming each factor doubles mortality risk, the confounding rate ratios for depression, antidepressant use, and unemployment were 1.10, 1.18, and 1.12. Lesser influential factors were benzodiazepine use, poverty, low societal status, sedentary lifestyle, and obesity. Depression and low socioeconomic status are strong candidates for producing the statistical association between long sleep and mortality, either as confounders or as causal intermediates. Future causal research on the effects of long sleep should include a detailed assessment of psychiatric disease and socioeconomic status.


Training for object recognition with increasing spatial frequency: A comparison of deep learning with human vision.
The ontogenetic development of human vision and the real-time neural processing of visual input exhibit a striking similarity-a sensitivity toward spatial frequencies that progresses in a coarse-to-fine manner. During early human development, sensitivity for higher spatial frequencies increases with age. In adulthood, when humans receive new visual input, low spatial frequencies are typically processed first before subsequent processing of higher spatial frequencies. We investigated to what extent this coarse-to-fine progression might impact visual representations in artificial vision and compared this to adult human representations. We simulated the coarse-to-fine progression of image processing in deep convolutional neural networks (CNNs) by gradually increasing spatial frequency information during training. We compared CNN performance after standard and coarse-to-fine training with a wide range of datasets from behavioral and neuroimaging experiments. In contrast to humans, CNNs that are trained using the standard protocol are very insensitive to low spatial frequency information, showing very poor performance in being able to classify such object images. By training CNNs using our coarse-to-fine method, we improved the classification accuracy of CNNs from 0% to 32% on low-pass-filtered images taken from the ImageNet dataset. The coarse-to-fine training also made the CNNs more sensitive to low spatial frequencies in hybrid images with conflicting information in different frequency bands. When comparing differently trained networks on images containing full spatial frequency information, we saw no representational differences. Overall, this integration of computational, neural, and behavioral findings shows the relevance of the exposure to and processing of inputs with variation in spatial frequency content for some aspects of high-level object representations.


Amphotericin B deoxycholate (d-AMB) use in cases with febrile neutropenia and fungal infections: lower toxicity with suitable premedication.
In spite of the development of new antifungal drugs, amphotericin B deoxycholate (d-AMB) remains the gold standard in the treatment of severe fungal infections in immunosuppressed hosts. However, d-AMB is a toxic drug, the most important dose-limiting toxicities being nephrotoxicity and infusion-related allergic reactions. Lipid and liposomal formulations of d-AMB have relatively lower toxicity and are considered alternative choices. However, the routine use of these formulations is limited by their higher cost. Using retrospective analysis, we explored the incidence of nephrotoxicity and allergic reactions requiring the cessation of conventional d-AMB in 113 cases treated with the drug. In contrast to knowledge in the relevant literature, we did not detect significant toxicity, which would have required discontinuation of the d-AMB treatment. Mean serum creatinine levels were 0.72 +/- 0.25 and 0.84 +/- 0.31 mg dl(-1) before and after therapy, respectively. Although the difference between creatinine levels before and after d-AMB is statistically significant, the creatinine level increased twofold in only eight cases. Mean serum potassium levels were 3.8 +/- 0.54 and 3.6 +/- 0.7 mmol l(-1) before and after d-AMB respectively. Potassium levels below 3 mmol l(-1) were found in 7 and 17 cases before and after d-AMB respectively. Potassium levels were statistically lower in cases with fungal mucositis. Severe infusion-related allergic reactions were observed in three cases. Antihistamine and corticosteroid were added to the treatment in these cases. With these findings, we can conclude that d-AMB is a tolerable, low cost drug which can be safely used provided there is suitable premedication and monitoring of blood urea nitrogen, serum potassium and magnesium levels.


Targeting CD133 antigen in cancer.
Much attention has been focused on CD133 as a marker of cancer cells with stem-cell-like ability. In the cancer stem cells (CSCs) model, only a small proportion of tumour cells are able to self-renew extensively, while the bulk of cells proceed to differentiate into committed heterogeneous clones. On the basis of the involvement of CSCs in tumourigenesis and treatment resistance, it is conceivable that only eradication of CSCs can lead to a cancer cure. To highlight the most recent evidence about the role of CD133 as a marker of CSCs in human tumours, and the therapeutic perspectives associated with its specific targeting. A literature search through Medline to locate published full articles using the following key words for selection: 'CD133 and cancer targeting', 'CD133 and chemo resistance', and 'CD133 and molecular pathways'. Only studies in English are considered. The role of CD133 as a marker of CSCs has been documented in several human neoplasms; its expression seems to predict unfavourable prognosis. Novel therapeutic strategies aimed at targeting molecular pathways critical for CD133+ CSCs survival are being examined.


Inflammatory Bowel Disease and Irritable Bowel Syndrome: What Differences in Mentalization Abilities? A Scoping Review.
Mentalization is a psychological process that enables individuals to understand the self and others in terms of intentional mental states. The aim of this scoping review was to provide an overview of the findings on mentalization in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). A literature search, in line with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols extension for Scoping Review guidelines, was conducted in the following bibliographic databases: PubMed, PsycINFO, and Scopus. Databases were queried using the following strings (with Boolean operators): ("mentaliz*" OR "metacogniti*" OR "theory of mind" OR "ToM" OR "reflective function*") AND ("irritable bowel syndrome" OR "IBS" OR "inflammatory bowel disease" OR "IBD"). In line with the eligibility criteria, seven articles were included. Results showed that no significant differences in metacognitive ability were found between patients in the IBD and IBS groups. This review revealed the mentalizing difficulties for patients with IBD and IBS. These results should be interpreted with caution since they are based on a few studies that used different instruments to assess mentalizing processes. Future studies are needed to clarify the role of mentalization in patients with these gastrointestinal conditions.


Cilostazol-imprinted polymer film-coated electrode as an electrochemical chemosensor for selective determination of cilostazol and its active primary metabolite.
An electrochemical chemosensor for cilostazol (CIL) determination was devised, engineered, and tested. For that, a unique conducting film of the functionalized thiophene-appended carbazole-based polymer, molecularly imprinted with cilostazol (MIP-CIL), was potentiodynamically deposited on a Pt disk electrode by oxidative electropolymerization. Thanks to electro-oxidation potentials lower than that of CIL, the carbazole monomers outperformed pyrrole, thiophene, and phenol monomers, in this electropolymerization. The pre-polymerization complexes quantum-mechanical and molecular dynamics analysis allowed selecting the most appropriate monomer from the three thiophene-appended carbazoles examined. The electrode was then used as a selective CIL chemosensor in the linear dynamic concentration range of 50 to 924 nM with a high apparent imprinting factor, IF = 10.6. The MIP-CIL responded similarly to CIL and CIL's pharmacologically active primary metabolite, 3,4-dehydrocilostazol (dhCIL), thus proving suitable for their determination together. Simulated models of the MIP cavities binding of the CIL, dhCIL, and interferences' molecules allowed predicting chemosensor selectivity. The MIP film sorption of CIL and dhCIL was examined using DPV by peak current data fitting with the Langmuir (L), Freundlich (F), and Langmuir-Freundlich (LF) isotherms. The LF isotherm best described this sorption with the sorption equilibrium constant (KLF) for CIL and dhCIL of 12.75 × 10-6 and 0.23 × 10-6 M, respectively. Moreover, the chemosensor cross-reactivity to common interferences study resulted in the selectivity to cholesterol and dehydroaripiprazole of 1.52 and 8.0, respectively. The chemosensor proved helpful in determining CIL and dhCIL in spiked human plasma with appreciable recovery (99.3-134.1%) and limit of detection (15 nM).


Mental health change in the transition to permanent supportive housing: The role of housing and social networks.
Permanent Supportive Housing (PSH) may improve homeless adults' mental health via housing stabilization and/or improved relational factors, however, the role of housing and social networks on PSH residents' mental health change is minimally understood. Interviews were conducted with a baseline sample of adults experiencing homelessness ( N = 421), across their initial year in PSH (3-months, 6-months, and 12-months). Generalized linear mixed models assessed changes in positive past-month psychiatric disability screenings (Modified-Colorado Symptom Index [MCSI]) and probable posttraumatic stress disorder (PC-PTSD) in controlled models, and between and within-subject effects of time-varying social network correlates on mental health changes. Compared with baseline, positive MCSI screens continuously decreased over time (56%, 54%, and 50%) while PC-PTSD screens declined initially (40%) with marginal decreases at remaining follow-ups (39% and 38%). These differences remained significant in controlled models. Gaining a romantic partner was associated with a longitudinal increase in a positive MCSI screening. Between subjects, emotional health counselors and conflicting network members were associated with an increased likelihood in positive screenings, while doctors and case managers were protective. Housing may facilitate positive changes in PSH residents' mental health, yet positive screenings remain high. Social network interventions that increase residents' positive interpersonal exchanges and prosocial relationships are warranted.


Contributions of total and regional fat mass to risk for cardiovascular disease in older women.
The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 +/- 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INS(AUC)) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INS(AUC)xGLU(AUC)), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INS(AUC), INS(AUC)xGLU(AUC), TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.


Predicting the distribution of Ixodes ricinus and Dermacentor reticulatus in Europe: a comparison of climate niche modelling approaches.
The ticks Ixodes ricinus and Dermacentor reticulatus are two of the most important vectors in Europe. Climate niche modelling has been used in many studies to attempt to explain their distribution and to predict changes under a range of climate change scenarios. The aim of this study was to assess the ability of different climate niche modelling approaches to explain the known distribution of I. ricinus and D. reticulatus in Europe. A series of climate niche models, using different combinations of input data, were constructed and assessed. Species occurrence records obtained from systematic literature searches and Global Biodiversity Information Facility data were thinned to different degrees to remove sampling spatial bias. Four sources of climate data were used: bioclimatic variables, WorldClim, TerraClimate and MODIS satellite-derived data. Eight different model training extents were examined and three modelling frameworks were used: maximum entropy, generalised additive models and random forest models. The results were validated through internal cross-validation, comparison with an external independent dataset and expert opinion. The performance metrics and predictive ability of the different modelling approaches varied significantly within and between each species. Different combinations were better able to define the distribution of each of the two species. However, no single approach was considered fully able to capture the known distribution of the species. When considering the mean of the performance metrics of internal and external validation, 24 models for I. ricinus and 11 models for D. reticulatus of the 96 constructed were considered adequate according to the following criteria: area under the receiver-operating characteristic curve > 0.7; true skill statistic > 0.4; Miller's calibration slope 0.25 above or below 1; Boyce index > 0.9; omission rate < 0.15. This comprehensive analysis suggests that there is no single 'best practice' climate modelling approach to account for the distribution of these tick species. This has important implications for attempts to predict climate-mediated impacts on future tick distribution. It is suggested here that climate variables alone are not sufficient; habitat type, host availability and anthropogenic impacts, not included in current modelling approaches, could contribute to determining tick presence or absence at the local or regional scale.


Inspiratory muscle training for improving inspiratory muscle strength and functional capacity in older adults: a systematic review and meta-analysis.
The ageing process can result in the decrease of respiratory muscle strength and consequently increased work of breathing and associated breathlessness during activities of daily living in older adults. This systematic review and meta-analysis aims to determine the effects of inspiratory muscle training (IMT) in healthy older adults. A systematic literature search was conducted across four databases (Medline/Pubmed, Web of Science, Cochrane Library CINAHL) using a search strategy consisting of both MeSH and text words including older adults, IMT and functional capacity. The eligibility criteria for selecting studies involved controlled trials investigating IMT via resistive or threshold loading in older adults (>60 years) without a long-term condition. Seven studies provided mean change scores for inspiratory muscle pressure and three studies for functional capacity. A significant improvement was found for maximal inspiratory pressure (PImax) following training (n = 7, 3.03 [2.44, 3.61], P = <0.00001) but not for functional capacity (n = 3, 2.42 [-1.28, 6.12], P = 0.20). There was no significant correlation between baseline PImax and post-intervention change in PImax values (n = 7, r = 0.342, P = 0.453). IMT can be beneficial in terms of improving inspiratory muscle strength in older adults regardless of their initial degree of inspiratory muscle weakness. Further research is required to investigate the effect of IMT on functional capacity and quality of life in older adults.


Development of PCR markers for Tamyb10 related to R-1, red grain color gene in wheat.
The grain color of wheat affects not only the brightness of flour, but also tolerance to preharvest sprouting. Grain color is controlled by dominant R-1 genes located on the long arm of hexaploid wheat chromosomes 3A, 3B, and 3D (R-A1, R-B1, and R-D1, respectively). The red pigment of the grain coat is composed of catechin and proanthocyanidin (PA), which are synthesized via the flavonoid biosynthetic pathway. We isolated the Tamyb10-A1, Tamyb10-B1, and Tamyb10-D1 genes, located on chromosomes 3A, 3B, and 3D, respectively. These genes encode R2R3-type MYB domain proteins, similar to TT2 of Arabidopsis, which controls PA synthesis in testa. In recessive R-A1 lines, two types of Tamyb10-A1 genes: (1) deletion of the first half of the R2-repeat of the MYB region and (2) insertion of a 2.2-kb transposon belonging to the hAT family. The Tamyb10-B1 genes of recessive R-B1 lines had 19-bp deletion, which caused a frame shift in the middle part of the open reading frame. With a transient assay using wheat coleoptiles, we revealed that the Tamyb10 gene in the dominant R-1 allele activated the flavonoid biosynthetic genes. We developed PCR-based markers to detect the dominant/recessive alleles of R-A1, R-B1, and R-D1. These markers proved to be correlated to known R-1 genotypes of 33 varieties except for a mutant with a single nucleotide substitution. Furthermore, double-haploid (DH) lines derived from the cross between red- and white-grained lines were found to necessarily carry functional Tamyb10 gene(s). Thus, PCR-based markers for Tamyb10 genes are very useful to detect R-1 alleles.


Spontaneous spinal epidural hematoma: literature review.
Review the current literature regarding spontaneous spinal epidural hematomas (SSEHs) and report on the known risk factors, evaluation, and treatment of this rare entity. A literature search was performed using PubMed and Ovid to identify articles pertaining to SSEHs. Due to the rarity of the pathologic entity, only scattered case reports and associated reviews are available. SSEHs are a rare yet potentially life-altering event. The underlying risk factors are poorly understood, and SSEHs present with minimal or no antecedent trauma. SSEHs warrant urgent surgical intervention given the associated risk of permanent neurologic sequelae. Given the potential for persistent neurologic deficits, physicians must entertain a clinical suspicion of SSEH when a patient presents with a history of back pain followed by neurologic deficits. Even without clear risk factors for hemorrhage, the appropriate evaluation to include advanced imaging studies should be obtained to allow for identification of this entity and urgent surgical management.


ABCG2 regulatory single-nucleotide polymorphisms alter in vivo enhancer activity and expression.
The expression and activity of the breast cancer resistance protein (ABCG2) contributes toward the pharmacokinetics of endogenous and xenobiotic substrates. The effect of genetic variation on the activity of cis-regulatory elements and nuclear response elements in the ABCG2 locus and their contribution toward ABCG2 expression have not been investigated systematically. In this study, the effect of genetic variation on the in vitro and in vivo enhancer activity of six previously identified liver enhancers in the ABCG2 locus was examined. Reference and variant liver enhancers were tested for their ability to alter luciferase activity in vitro in HepG2 and HEK293T cell lines and in vivo using a hydrodynamic tail vein assay. Positive in vivo single-nucleotide polymorphisms (SNPs) were tested for association with gene expression and for altered protein binding in electrophoretic mobility shift assays. Multiple SNPs were found to alter enhancer activity in vitro. Four of these variants (rs9999111, rs12508471, ABCG2RE1*2, and rs149713212) decreased and one (rs2725263) increased enhancer activity in vivo. In addition, rs9999111 and rs12508471 were associated with ABCG2 expression in lymphoblastoid cell lines, lymphocytes, and T cells, and showed increased HepG2 nuclear protein binding. This study identifies SNPs within regulatory regions of the ABCG2 locus that alter enhancer activity in vitro and in vivo. Several of these SNPs correlate with tissue-specific ABCG2 expression and alter DNA/protein binding. These SNPs could contribute toward reported tissue-specific variability in ABCG2 expression and may influence the correlation between ABCG2 expression and disease risk or the pharmacokinetics and pharmacodynamics of breast cancer resistance protein substrates.


Radiographic evaluation of the course of articular disease.
Radiological analysis is the single most attractive objective method for assessing the long-term anatomical effects of rheumatoid arthritis. Measurement of x-ray changes has given us our most important clues on the effectiveness of disease-modifying drugs. Although no single system has been adopted by all investigators to quantify radiological changes, most investigators have used joint counts or scores which have many properties of an interval scale to measure erosions and, at times, joint space narrowing. More extensive use of radiological analysis in therapeutic trials, if based on a thorough understanding of the natural history of radiological progression in rheumatoid arthritis, should provide a more accurate appraisal of our ability to modify the course of the disease.


Stomatal size in fossil plants: evidence for polyploidy in majority of angiosperms.
Three published estimates of the frequency of polyploidy in angiosperms (30 to 35 percent, 47 percent, and 70 to 80 percent) were tested by estimating the genome size of extinct woody angiosperms with the use of fossil guard cell size as a proxy for cellular DNA content. The inferred chromosome numbers of these extinct species suggest that seven to nine is the primitive haploid chromosome number of angiosperms and that most angiosperms (approximately 70 percent) have polyploidy in their history.


Temporal trends of decabromodiphenyl ether and emerging brominated flame retardants in dust, air and window surfaces of newly built low-energy preschools.
The envelope of low-energy buildings is generally constructed with significant amounts of plastics, sealants and insulation materials that are known to contain various chemical additives to improve specific functionalities. A commonly used group of additives are flame retardants to prevent the spread of fire. In this study, decabromodiphenyl ether (BDE-209) and fourteen emerging brominated flame retardants (BFRs) were analyzed in indoor dust, air and on the window surface of newly built low-energy preschools to study their occurrence and distribution. BDE-209 and decabromodiphenyl ethane (DBDPE) were frequently detected in the indoor dust (BDE-209: <4.1-1200 ng/g, DBDPE: <2.2-420 ng/g) and on window surfaces (BDE-209: <1000-20 000 pg/m2 , DBDPE: <34-5900 pg/m2 ) while the other thirteen BFRs were found in low levels (dust: <0.0020-5.2 ng/g, window surface: 0.0078-35 pg/m2 ). In addition, the detection frequencies of BFRs in the indoor air were low in all preschools. Interestingly, the dust levels of BDE-209 and DBDPE were found to be lower in the environmentally certified low-energy preschools, which could be attributed to stricter requirements on the chemical content in building materials and products. However, an increase of some BFR levels in dust was observed which could imply continuous emissions or introduction of new sources.


cGMP suppresses GTPase activity of a portion of transducin equimolar to phosphodiesterase in frog rod outer segments. Light-induced cGMP decreases as a putative feedback mechanism of the photoresponse.
In rod photoreceptor cells, the light response is triggered by an enzymatic cascade that causes cGMP levels to fall: excited rhodopsin (Rho*)----rod G-protein (transducin, Gt)----cGMP-phosphodiesterase (PDE). This results in the closure of plasma membrane channels that are gated by cGMP. PDE activation by Gt occurs when GDP bound to the alpha-subunit of Gt (Gt alpha) is exchanged with free GTP. The interaction of Gt alpha-GTP with the gamma-subunits of PDE releases their inhibitory action and causes cGMP hydrolysis. Inactivation is thought to be caused by subsequent hydrolysis of Gt alpha-GTP by an intrinsic Gt-GTPase activity. Here we report that there are two portions of Gt in frog rod outer segments (ROS) expressing different rates of GTP hydrolysis: 19.5 +/- 3 mmol of Gt/mol of Rho, equivalent to that amount which participates in PDE activation, hydrolyzing GTP at a rate of approximately 0.6 turnover/s ("fast") and the remaining Gt (80.5 +/- 3 mmol/mol Rho) hydrolyzing GTP at a rate of 0.058 +/- 0.009 turnover/s. Fast GTPase activity is abolished in the presence of cGMP. This effect occurs over the physiological range of cGMP concentration changes in ROS, half-saturating at approximately 2 microM and saturating at 5 microM cGMP. cGMP-dependent suppression of GTPase is specific for cGMP; cAMP in millimolar concentration does not affect GTPase, while the poorly hydrolyzable cGMP analogue, 8-bromo-cGMP, mimics the effect. GTPase regulation by cGMP is not affected by Ca2+ over the concentration range 5-500 nM, which spans the physiological changes in cytoplasmic Ca2+ in rod cells. We suggest that the fast cGMP-sensitive GTPase activity is a property of the Gt that activates PDE. In this model, cGMP serves not only as a messenger of excitation but also modulates GTPase activity, thereby mediating negative feedback regulation of the pathway via PDE turnoff: a light-dependent decrease in cGMP accelerates the hydrolysis of GTP bound to Gt, resulting in the rapid inactivation of PDE.


Dromedary camel CD14high MHCIIhigh monocytes display inflammatory properties and are reduced in newborn camel calves.
In human and different animal species, blood monocytes are classified based on their expression pattern of different monocytic markers into phenotypically and functionally different subsets. In the current study, we used flow cytometry and monoclonal antibodies to CD172a, CD14, CD163 and MHCII to identify monocyte subsets in peripheral blood of dromedary camels. Based on CD14, CD163 and MHCII expression, camel CD172a + monocytes were divided into three subsets: The major subpopulation of camel monocytes (mo-I) showed high expression of CD14 and CD163, but low expression of MHCII. A second subset of monocytes (mo-II) expressed highly all three markers, CD14, CD163 and MHCII. A third monocyte subset (mo-III) displayed low expression of CD14 and CD163 with high MHCII expression. While the two MHCIIhigh subsets (mo-II and mo-III) showed higher expression of CD11a in comparison to the MHCIIlow subset (mo-I), CD18 and CD11b were highest expressed on the two CD14high subsets (mo-I and mo-II). Bacterial stimulation of camel leukocytes identified mo-II cells as an antimicrobial monocyte subset with the highest phagocytic and ROS production capacity. The comparison of monocyte counts and phenotype between newborn calves and adult camels revealed significantly reduced numbers of mo-II cells in newborn animals. Monocytes of newborns expressed significantly more CD172a and CD163 molecules but less CD14 and MHCII molecules than monocytes of adult camels. Camel monocyte subsets, mo-I, mo-II and mo-III are counterparts of bovine classical, intermediate and non-classical monocytes respectively. The distribution of camel monocyte subsets is influenced by age.


Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine.
Genetic modification of tumour cells with the GM-CSF encoding gene renders these cells more potent, as autologous tumour cell vaccine, than their wild-type counterparts. However, autologous vaccines are impractical for wide-scale clinical use and we have therefore investigated the efficacy of the GM-CSF genetic modification approach with an allogeneic whole cell tumour vaccine. In this report, we show that the allogeneic K1735-M2 (H-2k) melanoma cell vaccine induces a specific protective anti-tumour response against the syngeneic B16-F10 (H-2b) melanoma tumour in C57BL/6J mice. In vitro T cell work demonstrated that vaccination of animals with the allogeneic cell vaccine generated cytotoxic T cells specific for the autologous tumour. In vivo T cell subset depletion experiments also illustrated that this anti-tumour effect was mediated by both CD4+ve and CD8+ve T cells, suggesting that the allogeneic vaccine may operate through the 'cross-priming' phenomenon whereby tumour antigens are processed and presented to T cells by the host's own antigen presenting cells (APC). Thus, we transduced K1735-M2 cells with a GM-CSF expressing retroviral vector and showed anti-tumour activity of the GM-CSF secreting K1735-M2 cells as a therapeutic vaccine against the syngeneic B16-F10 tumour. Our data imply that GM-CSF genetically modified allogeneic whole cell tumour vaccines could be successful in the clinic. In addition, more potent combination gene therapy strategies could be tested using this therapeutic allogeneic vaccine model.


[X-ray diagnostic parallels in estimation of the degree of portohepatic circulation reduction in patients with liver cirrhosis].
The data obtained in a retrospective analysis, angiographic and hepatoscintigraphic examinations of 86 patients (aged from 12 to 64 years) with liver cirrhosis (LC) treated during the period from 1998 through 2003 were analyzed. Among them there were 64 men and 22 women. The investigations performed have shown that the angiographic data obtained in LC patients determine not only the topographic interaction of the major and collateral vessels of the porto-lienal pool that is of principal significance in the decision for the method of surgical correction in portal hypertension but also allow an estimation of the picture of the hepatopetal blood flow inversion. The data obtained allowed the authors to define three degrees of reduction of the hepatopetal blood flow. A conclusion was made that the degree of reduction of the hepatopetal blood flow when compared was the findings of angiographic and radionuclide examinations were of great prognostic significance for an estimation of the necessary decompression and possible maximal preservation of the hepatopetal blood flow with respect to the preoperative level.


Tuberculin skin test result and risk of death among persons with active TB.
Although the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10-25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death. We analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death. Of 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30-0.36). A negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death.