FTIR matrix isolation study of CDF3 in the region of CD stretching vibration: The spectroscopic manifestation of the Fermi resonance effects.

The IR spectra of CDF3 in the solid Ar and N2 matrices were measured and analyzed in the region of the Fermi polyads 2ν4/ν1/2ν2/ν4 + ν5, complicated by a close Fermi resonance ν4/ν3 + ν6. The symmetry lifting effect, observed in the N2 matrix, was found helpful for an accurate assignment of the individual components. The anharmonic calculation of the potential energy surface and the dipole moment function was performed on the MP2/aug-cc-pVTZ level. The unperturbed values of vibrational eigenstates were determined in the region of ν1 (CD stretching vibration) in both matrices. The experimental findings and theoretical analysis are in good agreement.

Noncovalent interactions between isoflurane and dimethyl ether. Spectroscopic evidence of trimer formation.

The IR spectra of isoflurane + dimethyl ether mixtures dissolved in liquid Kr are registered at T ~118-160 K. The results obtained at a wide range of relative concentrations suggest the formation of complexes stabilized by non-covalent interactions of H-bond type. Large excess of DME and low temperature favor trimer formation stabilized by interactions between two DME moieties and both CH groups of isoflurane predominantly. Estimations based on ab initio calculation of spectroscopic and thermodynamic parameters confirm the experimental findings.

The infrared study of fluoroform + methyl fluoride mixtures in argon and nitrogen matrices. Evidence of nonlinear blue-shifting complex formation.

The FTIR spectra of fluoroform + methyl fluoride mixtures trapped in argon and nitrogen matrices are studied at T~10-30 K. Spectroscopic changes observed in the region of the CH stretching mode of fluoroform are typical for weak blue shifting H - bonds of CH⋯F type. The degeneracy lifting effect found on E - type bands of fluoroform interacted with methyl fluoride suggests the complex formation of a nonlinear form. The experimental results are confirmed by ab initio calculations of fluoroform + methyl fluoride based on the second order Møller-Plesset theory of perturbations utilizing advanced basis set. Nonlinear complexes are stabilized by the basic CH⋯F interaction and additionally by van der Waals-type CD⋯FC contacts between deuterated methyl fluoride and fluoroform.

Bilateral cingulum fiber reductions in temporal lobe epilepsy with unilateral hippocampal sclerosis.

PURPOSE: To evaluate whether white matter tracts within the Papez circuit are altered in patients with unilateral hippocampal sclerosis (HS). METHODS: Twenty patients with histologically proven unilateral HS and 20 age-matched controls were studied with a 3T Epilepsy-dedicated MRI protocol including a MPRAGE sequence for hippocampus volumetry and a diffusion tensor imaging (DTI) sequence (61 diffusion-encoding directions, 2×2×2mm3 voxels) for diffusion tensor tractography (DTT). An energy-based global tracking algorithm was used to calculate streamline counts (SC) and fractional anisotropy (FA) of cingulate, fornix, and mammillo-thalamic tracts, respectively. RESULTS: Sclerotic hippocampi were significantly smaller compared to the contralateral side and to age-matched controls. Cingulum SC but not FA were reduced on the hippocampal sclerosis (258+81.0) and contralateral side (271+85.6) compared to age-matched controls (447+138). CONCLUSION: Focusing on white matter tracts of the Papez circuit we showed that in patients with intractable temporal lobe epilepsy unilateral hippocampal sclerosis is associated with a bilateral reduction of cingulum association fibers projecting from the cingulate gyrus to the parahippocampal gyrus.

How to reduce the number of rating scale items without predictability loss?

Rating scales are used to elicit data about qualitative entities (e.g., research collaboration). This study presents an innovative method for reducing the number of rating scale items without the predictability loss. The "area under the receiver operator curve method" (AUC ROC) is used. The presented method has reduced the number of rating scale items (variables) to 28.57% (from 21 to 6) making over 70% of collected data unnecessary. Results have been verified by two methods of analysis: Graded Response Model (GRM) and Confirmatory Factor Analysis (CFA). GRM revealed that the new method differentiates observations of high and middle scores. CFA proved that the reliability of the rating scale has not deteriorated by the scale item reduction. Both statistical analysis evidenced usefulness of the AUC ROC reduction method.

FTIR cryospectroscopic and ab initio studies of desflurane-dimethyl ether H-bonded complexes.

The IR spectra of mixtures of desflurane and dimethyl ether are studied with the help of FTIR cryospectroscopy in liquefied Kr at T~118-158K. Comparative analysis of the experimental data and results of ab initio calculations show that either of the two C-H groups of desflurane is involved in heterodimer formation of comparable strengths. The blue frequency shift is found for stretching vibrations of those C-H donors which directly participate in H-bond formation. Additionally the complexes are stabilized by weaker contacts between hydrogen atoms of dimethyl ether and fluorine atoms of desflurane.

How to manage chronic urticaria 'beyond' guidelines: a practical algorithm.

Chronic urticaria (CU) is a disease characterized by pruritic weals, angio-oedema or both occurring for at least 6 weeks. It encompasses spontaneous and inducible urticarias. The national and international guidelines outline the principles of treatment. Omalizumab, an anti-immunoglobulin E monoclonal antibody, has transformed the management of many severe and treatment-refractory patients. However, current UK guidance on its use does not address the needs of those with less severe disease, inducible urticarias, idiopathic histaminergic angio-oedema without weals as a presentation of CU and omalizumab non-responders. Our algorithm and a summary of the evidence to support its principles offers guidance and a more systematic targeted approach to using a range of 'off-label' agents for specific phenotypes of CU. It will be of use when guideline-recommended mast cell mediator antagonists fail to control symptoms and/or using omalizumab is ineffective, not practical or unfunded.

Infrared spectroscopy and ab initio study of hydrogen bonded Cl3CD·N(CH3)3 complex in the gas phase.

FTIR spectra of the gas phase Cl3CD+TMA mixture have been studied at room temperature in ∼800-4000 cm(-1) frequency domain. The formation of the H-bonded Cl3CD…TMA complex has been detected. Spectroscopic parameters of the band ascribed to the complex were evaluated. MP2 frozen core ab initio calculations have been carried out with the Pople-type 6-311++G(d,p) basis set. The equilibrium geometries and harmonic vibrational frequencies of the complex were obtained using CP-corrected gradient techniques. The ''freq=anharm'' option has been tested for Cl3CD monomer and Cl3CD…TMA complex to examine possible anharmonic effects on the vibrations localized on the proton donor. The effects of Darling-Dennison and Fermi resonances on the frequency of the stretching vibration of the CH proton donor were analyzed.

Management of hypersensitivity reactions to anti-D immunoglobulin preparations.

RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk.

Bayesian QTL analyses using pedigreed families of an outcrossing species, with application to fruit firmness in apple.

KEY MESSAGE: Proof of concept of Bayesian integrated QTL analyses across pedigree-related families from breeding programs of an outbreeding species. Results include QTL confidence intervals, individuals' genotype probabilities and genomic breeding values. Bayesian QTL linkage mapping approaches offer the flexibility to study multiple full sib families with known pedigrees simultaneously. Such a joint analysis increases the probability of detecting these quantitative trait loci (QTL) and provide insight of the magnitude of QTL across different genetic backgrounds. Here, we present an improved Bayesian multi-QTL pedigree-based approach on an outcrossing species using progenies with different (complex) genetic relationships. Different modeling assumptions were studied in the QTL analyses, i.e., the a priori expected number of QTL varied and polygenic effects were considered. The inferences include number of QTL, additive QTL effect sizes and supporting credible intervals, posterior probabilities of QTL genotypes for all individuals in the dataset, and QTL-based as well as genome-wide breeding values. All these features have been implemented in the FlexQTL(™) software. We analyzed fruit firmness in a large apple dataset that comprised 1,347 individuals forming 27 full sib families and their known ancestral pedigrees, with genotypes for 87 SSR markers on 17 chromosomes. We report strong or positive evidence for 14 QTL for fruit firmness on eight chromosomes, validating our approach as several of these QTL were reported previously, though dispersed over a series of studies based on single mapping populations. Interpretation of linked QTL was possible via individuals' QTL genotypes. The correlation between the genomic breeding values and phenotypes was on average 90 %, but varied with the number of detected QTL in a family. The detailed posterior knowledge on QTL of potential parents is critical for the efficiency of marker-assisted breeding.

Administration of yellow fever vaccine in patients with egg allergy.

BACKGROUND: The population of large parts of Africa, South America and travellers to these areas are at risk of yellow fever (YF) with a 50% mortality risk. Yellow fever vaccine (YFV) propagated in hens' eggs confers protection in 95% of the vaccinated. The rate of anaphylaxis for YFV ranges from 0.42 to 1.8/100,000 doses with most cases considered to be due to egg allergy. Egg allergy is a contraindication for the YFV. Nevertheless, the potential fatal sequelae from YF give the incentive to protect everyone at risk irrespective of their allergic status. METHODS: Six subjects who had had a recent reaction to egg and who were travelling to endemic areas (3 adults and 3 children) underwent skin prick tests (SPT) with undiluted YFV and egg extract. Intradermal tests for YFV were undertaken at a 1:10 dilution. In 4 egg-allergic patients with a positive SPT to YFV, a 7-step desensitization protocol was used. A 2-step (10 + 90%) protocol was used in the 2 subjects with a negative YFV SPT. Premedication was not administered. RESULTS: All 6 patients were successfully vaccinated. Four patients completed desensitization: 1 developed mild local erythema at the injection site, 1 had fleeting generalized urticaria with local erythema/angioedema and 2 did not experience any adverse reactions. Patients who received YFV in 2 steps developed no adverse reactions. CONCLUSIONS: We describe the successful administration of YFV in 6 egg-allergic patients. The Cambridge Allergy 7-step protocol allows for its safe administration in patients with positive SPT to YFV. A 2-step protocol can be used in patients with negative YFV SPT.

Paracetamol hypersensitivity: clinical features, mechanism and role of specific IgE.

BACKGROUND: Paracetamol is a common antipyretic/analgesic and a component of many prescription and over- the- counter preparations. Hypersensitivity reactions to paracetamol appear to be increasing, but there are few prevalence data. The mechanism is poorly understood. We identified the clinical features of 32 patients with suspected paracetamol allergy, investigated the underlying mechanism and examined co-existing non-steroidal anti-inflammatory drug (NSAID) tolerance. METHODS: A clinical history was taken and skin tests and an oral challenge were performed in 32 patients with suspected paracetamol allergy. RESULTS: Patients presented with a combination of urticaria, angio-oedema (face, hands), erythema (cutaneous features in 94%), dyspnoea (including laryngeal oedema), rhinoconjunctivitis, cough, abdominal pain and anaphylaxis. Two patients had a positive skin prick test (SPT) and unequivocal history of acute urticaria/facial angio-oedema/conjunctivitis/cough after paracetamol with no other triggers. One patient had a positive intradermal test. Oral challenge was positive in 15 of 31 patients (including self-challenge in 4), triggering (a combination of) rhinitis, conjunctivitis, pruritus, erythema, urticaria, angio-oedema, dyspnoea and abdominal pain. Sensitivity was evident in 1 patient on the basis of the patient's history. Overall, paracetamol hypersensitivity was confirmed in 16 of the 32 patients (50%). Twelve of the 16 paracetamol-allergic patients (75%) tolerated NSAIDs (negative challenge in 6, negative history in 6). Four of these 16 patients (25%) were intolerant of NSAIDs (positive challenge in 1, self-challenge in 3). CONCLUSIONS: In past reports on paracetamol hypersensitivity, only single cases of a positive SPT and detectable specific IgE have been described. Our data confirm that specific IgE may be a mechanism underlying paracetamol hypersensitivity, as in this series 18.8% of the patients had specific IgE. In 81.2% of patients, negative skin tests did not exclude paracetamol hypersensitivity, suggesting that it may be mediated by leukotrienes. However, three quarters of our patients tolerated NSAIDs, implicating an alternative mechanism. In patients with suspected paracetamol allergy, skin tests should be performed in addition to clinical history and oral challenge.

Strong and weak effects caused by non covalent interactions between chloroform and selected electron donor molecules.

The FTIR spectra of chloroform (Cl(3)CH) in mixtures with various electron donors (B = CH(3)CCH, HCCH, NCCD(3), ClCD(3) and CO) have been studied in liquefied Kr. Spectroscopic evidence of weak H-bond formation has been found. The relative stability of some complexes has been evaluated from temperature studies of integrated intensities of vibrational bands attributed to monomer and complex species. A weak red shift of the stretching vibration of chloroform involved in H-bonding with CH(3)CCH and HCCH having π-electron area was observed. However, in the case of interactions with NCCD(3) and CO, a weak blue shift was detected. In most of the cases, a noticeable increase in the integrated intensity of the CH stretching band was found. Ab initio MP2/6-311++G(2d,2p) a priori counterpoise corrected calculations have been performed for a series of Cl(3)CH and B. Stationary points at the potential energy surface were examined and the structures related to the real minima have been found. The calculations reproduce the majority of experimental results. It has been found that the commonly used correlation between the frequency shift of the CH stretching vibration of the proton donor subunit and the change in CH bond length can fail in the case of the complexes characterized by a weak frequency shift effect.

Infrared spectra and relative stability of the F3CH/NH3 H-bonded complex in liquefied Xe.

FTIR spectra of mixtures of fluoroform (F3CH) and ammonia (NH3), have been studied in liquid xenon between 5400 and 500 cm-1. Spectroscopic evidence for the formation of a hydrogen bonded complex has been found and the complexation enthalpy Delta(LXe)H degrees in the temperature interval between 173 and 215 K, was determined to be 14.4 (7) kJ mol-1. The parallel fundamentals nu1 and nu2 of ammonia reveal a strong narrowing effect upon complex formation, whereas the perpendicular fundamentals nu3 and nu4 show a modest decrease of their width. CP corrected ab initio calculations at the MP2(FULL)/6-311++G(3df,2pd) level predict a linear geometry for the complex, characterized by a small red shift of the CH stretch frequency of fluoroform. The ab initio interaction energy was found to be compatible with the isolated molecule complexation energy extrapolated from the experimental Delta(LXe)H degrees .

IR spectra of CH3F in liquid and solid noble gas solutions.

The IR absorption spectra of CH3F doped Ar, Kr and Xe solutions have been recorded near the melting point. The full widths at half maximum of fundamental bands increase noticeably after crystallization of the Xe and Kr solutions. A slight narrowing of the bands is observed just below the freezing point of the Ar solution. Treated in the framework of the Debye model for the J-diffusion of a symmetric top rotation, the results suggest a weaker perturbation of rotational motion of CH3F in the ordered Xe and Kr solids at least near the freezing point. At the same time, molecular rotation becomes more hindered when going to solid Ar. The broadening effect has been found to correlate with a hopping increase of the vibrational energy relaxation time, measured by the IR-IR double resonance method.

Co-localization of TFF3 peptide and oxytocin in the human hypothalamus.

TFF-peptides (formerly P domain peptides, trefoil factors) are typical secretory products of many mucous epithelial cells. TFF3 is also synthesized in the hypothalamus and has anxiolytic or anxiogenic activities when injected into the rat amygdala. Here we show by immunohistochemistry that TFF3 is localized to a distinct population of neurons of the human hypothalamic paraventricular and supraoptic nuclei. Generally, TFF3-positive cells are co-localized in oxytocin-producing cells and not in vasopressin-producing cells. Relatively large amounts of TFF3-but not TFF1 and TFF2-are present in the posterior lobe of the human pituitary, where it is probably released into the bloodstream. Furthermore, TFF3 was also detectable in human postmortem cerebrospinal fluid.

[Anxiety and depression in post-traumatic disorders]. / Lek i depresja w zespole stresu pourazowego.

The paper presents the research results of those who had PTSD and were examined. The group was of 90 persons, who were former political prisoners in Poland. The State and Trait of Anxiety Inventory and the Hamilton Depression Rating Scale were applied in order to measure the intensity of anxiety and depressive symptoms. 76% of those examined had nightmares. This group is also significant for its' high level momentary anxiety, anxiety as a persistent personality trait as well as uncommon (20%) incidence of depression. The group of those that do not remember nightmares (24% of all those examined) is characterised by a lower level of anxiety reaction and common incidence of depression (84.2%). The article is ended with a discussion on the meaning of the results for the diagnosis and treatment of post-traumatic disorders.

Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1.

The rate of transcription of several genes encoding proteins involved in O(2) and energy homeostasis is controlled by hypoxia-inducible factor-1 (HIF-1), a heterodimeric DNA binding complex composed of alpha and beta subunits. HIF-1 is considered the primary trans-acting factor for the erythropoietin (EPO) and vascular endothelial growth factor (VEGF) genes. Since EPO gene expression is inhibited by the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), while no such effect has been reported with respect to the VEGF gene, we investigated the effects of IL-1beta and TNF-alpha on the activation of the HIF-1 DNA-binding complex and the amount of HIF-1alpha protein in human hepatoma cells in culture. Under normoxic conditions, both cytokines caused a moderate activation of HIF-1 DNA binding. In hypoxia, cytokines strongly increased HIF-1 activity compared with the effect of hypoxia alone. Only IL-1beta increased HIF-1alpha protein levels. In transient transfection experiments, HIF-1-driven reporter gene expression was augmented by cytokines only under hypoxic conditions. In contrast to their effect on EPO synthesis, neither IL-1beta nor TNF-alpha decreased VEGF production. The mRNA levels of HIF-1alpha and VEGF were unaffected. Thus, cytokine-induced inhibition of EPO production is not mediated by impairment of HIF-1 function. We propose that HIF-1 may be involved in modulating gene expression during inflammation.

Induction of TFF1 gene expression in pancreas overexpressing transforming growth factor alpha.

BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. METHODS: Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor alpha (TGF-alpha), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-alpha. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-alpha exhibited pronounced TFF1 immunoreactivity. CONCLUSIONS: Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5'-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-alpha is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-alpha.