Correction: The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab.

In the abstract and in other parts of the manuscript the authors wrote that the mutation rs396991 causes a valine (V) to phenylalanine (F) substitution at position 157. However, the correct codon number is 158. These errors have not been fixed in the original Article.

Analysis of an in-house technique for temporary mandibulotomy and its impact on postoperative radiotherapy.

The purpose of this study was to describe a newly developed procedure for temporary mandibulotomy and subsequent osteosynthesis. Clinical outcomes were evaluated, including complications and the impact on postoperative treatment, particularly postoperative radiotherapy. Twenty-four patients underwent temporary mandibulotomies for the surgical resection of malignancies located in the posterior oral or oropharyngeal region. All were treated with postoperative radiotherapy. An angulated median mandibulotomy was followed by osteosynthesis with three anchor screws directed towards the inferior aspect of the mandible. Anchor screws are modified conventional lag screws that include an additional biconcave washer. This modification prevents the screw heads from cracking into the cancellous bone during tightening, improving their biomechanical qualities considerably. Insertion of screws at any angle to the bony surface therefore becomes possible, which is a precondition for this technique. Minor complications occurred in two patients in the early postoperative period. However, complications causing bony non-union, leading to postponed postoperative radiotherapy were not noted in this cohort.

Nanoengineering ABO3 active sites from low-energy routes (TX100-stabilised water-in-oil microemulsions, surface segregation and surface complexation on colloidal AlOOH/sol-gel Al2O3 surfaces) for pollution control catalysis.

It is shown that water-in-oil microemulsions (m/e or µE) can produce BaCeO3 (BCO) and LaCoO3 (LCO) precursors. The nanoparticles (NPs) adsorb on AlOOH sols, in much the same way as Turkevich previously immobilised platinum group metal sols. BCO is active in CO and propane oxidation and NO removal under stoichiometric exhaust conditions, but LCO is a better oxidation catalyst. Activity was also seen when Ba,Ce and La,Co are inserted into/segregate at the surface of AlOOH/Al2O3. However, there is only formation of low levels of BCO, CAIO3 (CAO), LCO and LaAIO3 (LAO) perovskites, along with aluminates and separate oxides. The complexing of cations by AlOOH surface-held oxalate ions, albeit with different efficiencies, has also been explored. All three routes yield active catalysts with micro-domains of crystallinity; microemulsions produce the best defined perovskite NPs, but even those from surface segregation have higher turnover numbers than traditional Pt catalysts. Perovskite NPs may open up green chemistry for air pollution control that is consistent with a circular economy.

The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab.

FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5.5 vs 4.1 months, P=0.02; median overall survival: 10.2 vs 7.2 months, P=0.04). In multivariate analysis, the FCGR2A and 3A genotypes as well as the time between initial diagnosis and relapse of disease not amenable to curative therapy remained the only independent prognostic factors for PFS. The results are in line with previous reports in colorectal cancer patients and confirm the possible value of genetic polymorphisms of immunocompetent cells for the success of cetuximab treatment.

Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.

OBJECTIVE: The goal of the present study was to identify differences in gene expression between SAT, VAT and EAT depots in Class III severely obese individuals. DESIGN: Human subcutaneous (SAT) and visceral (VAT) adipose tissues exhibit differential gene expression profiles. There is little information, however, about the other proximal white adipose tissue, epigastric (EAT), in terms of its function and contribution to metabolism. SUBJECTS AND METHODS: Using RNA from adipose biospecimens obtained from Class III severely obese patients undergoing open Roux-en-Y gastric bypass surgery, we compared gene expression profiles between SAT, VAT and EAT, using microarrays validated by real-time quantitative PCR. RESULTS: The three depots were found to share 1907 genes. VAT had the greatest number of genes (66) expressed exclusively in this depot, followed by SAT (23), and then EAT (14). Moreover, VAT shared more genes with EAT (65) than with SAT (38). Further analyses using ratios of SAT/EAT, VAT/EAT and SAT/VAT identified specific as well as overlapping networks and pathways of genes representing dermatological diseases, inflammation, cell cycle and growth, cancer and development. Targeted analysis of genes, having a role in adipose tissue development and function, revealed that Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1-α) that regulates the precursor of the hormone Irisin (FNCD5) were abundantly expressed in all three fat depots, along with fibroblast growth factors (FGF) FGF1, FGF7 and FGF10, whereas, FGF19 and FGF21 were undetectable. CONCLUSIONS: These data indicate that EAT has more in common with VAT, suggesting similar metabolic potential. The human epigastric adipose depot could have a significant functional role in metabolic diseases and should be further investigated.

Anorexia nervosa trios: behavioral profiles of individuals with anorexia nervosa and their parents.

BACKGROUND: Anorexia nervosa (AN) is associated with behavioral traits that predate the onset of AN and persist after recovery. We identified patterns of behavioral traits in AN trios (proband plus two biological parents). METHOD: A total of 433 complete trios were collected in the Price Foundation Genetic Study of AN using standardized instruments for eating disorder (ED) symptoms, anxiety, perfectionism, and temperament. We used latent profile analysis and ANOVA to identify and validate patterns of behavioral traits. RESULTS: We distinguished three classes with medium to large effect sizes by mothers' and probands' drive for thinness, body dissatisfaction, perfectionism, neuroticism, trait anxiety, and harm avoidance. Fathers did not differ significantly across classes. Classes were distinguished by degree of symptomatology rather than qualitative differences. Class 1 (approximately 33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2 ( approximately 43%) included probands with marked elevations in drive for thinness, body dissatisfaction, neuroticism, trait anxiety, and harm avoidance and mothers with mild anxious/perfectionistic traits. Class 3 (approximately 24%) included probands and mothers with elevations on ED and anxious/perfectionistic traits. Mother-daughter symptom severity was related in classes 1 and 3 only. Trio profiles did not differ significantly by proband clinical status or subtype. CONCLUSIONS: A key finding is the importance of mother and daughter traits in the identification of temperament and personality patterns in families affected by AN. Mother-daughter pairs with severe ED and anxious/perfectionistic traits may represent a more homogeneous and familial variant of AN that could be of value in genetic studies.

A meta-analytic review of coping with illness: do causal attributions matter?

OBJECTIVE: The present meta-analytic review assessed the relations between causal attributions, coping, and psychological adjustment in individuals with physical illnesses or undergoing medical procedures. A theoretical model predicting psychological adjustment was proposed. It was hypothesized that causal attributions would be both directly related to psychological adjustment and indirectly related to psychology adjustment via coping strategies. METHODS: Relevant methodological and statistical information was extracted from 27 target studies. Weighted correlations from 27 studies were used as the unit of analysis to test the theoretical model. RESULTS: Overall, internal, unstable, and controllable attributions were indirectly associated with positive psychological adjustment through the use of Approach and Emotion-Focused coping (P<.01). In addition, stable and uncontrollable attributions were indirectly associated with negative psychological adjustment through the use of Avoidance coping (P<.01). CONCLUSION: These results suggest that attributions guide some motivated cognitions and behaviors within the context of illness, and are related to specific coping strategies. The discussion focuses on the predictive validity of these findings using the proposed theoretical model.

Modeling stress: a methodological review.

Covariance structure modeling (CSM) is increasingly being utilized in stress research. For this reason, a methodological review was undertaken to assess how well applied researchers have recognized the shortcomings and recommendations commonly espoused in the mathematical and statistical CSM literature. In reviewing a broad cross section of research (n = 50), many problems were noted. For example, data sets were rarely checked for nonnormality even though conventional CSM estimation procedures (e.g., maximum likelihood) are based on the assumption that the data come from a multivariate normal distribution, equivalent models were neither evaluated nor even acknowledged, and the majority of favored models were modified based on empirical rather than theoretical considerations. The results suggest that applied stress researchers have inadequate knowledge of the technical CSM literature, which has potential ramifications for theory development.

Maternal plasma corticotropin-releasing hormone associated with stress at 20 weeks' gestation in pregnancies ending in preterm delivery.

OBJECTIVE: This study tested the hypothesis that maternal stress is associated with elevated maternal levels of corticotropin releasing hormone and activation of the placental-adrenal axis before preterm birth. STUDY DESIGN: In a behavior in pregnancy study, 524 ethnically and socioeconomically diverse women were followed up prospectively and evaluated at 3 gestational ages: 18 to 20 weeks, 28 to 30 weeks, and 35 to 36 weeks. Maternal variables included demographic data, medical conditions, perceived stress level, and state anxiety. Maternal plasma samples were collected at each gestational age. Eighteen case patients with spontaneous onset of preterm labor were matched against 18 control subjects who were delivered at term, and their samples were assayed for corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol by means of radioimmunoassay. Statistical tests were used to examine mean differences in these hormones. In addition, the relationship between stress level and each hormone was tested with a Pearson correlation coefficient and hierarchic multiple regressions in each group. RESULTS: Patients who had preterm delivery had significantly higher plasma corticotropin-releasing hormone levels than did control subjects at all 3 gestational ages (P <.0001). Analyses did not find any differences in reported levels of stress between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation. A hierarchic multiple regression indicated that maternal stress level at 18 to 20 weeks' gestation and maternal age accounted for a significant amount of variance in corticotropin-releasing hormone at 28 to 30 weeks' gestation, after controlling for corticotropin-releasing hormone at 18 to 20 weeks' gestation (P <. 001). In addition, patients who were delivered preterm had significantly elevated plasma levels of adrenocorticotropic hormone at all 3 gestational ages (P <.001) and significantly elevated cortisol levels at 18 to 20 weeks' gestation and 28 to 30 weeks' gestation (P <.001). CONCLUSION: Maternal plasma levels of corticotropin-releasing hormone are significantly elevated at as early as 18 to 20 weeks' gestation in women who are subsequently delivered preterm. Changes in corticotropin-releasing hormone between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation are associated with maternal age and stress level at 18 to 20 weeks' gestation. Maternal stress and corticotropin-releasing hormone levels may be potential markers for the patient at risk for preterm birth. Activation of the placental maternal pituitary-adrenal axis is consistent with the classic endocrine response to stress.

A comparison of the factor structure of processing speed for younger and older adults: testing the assumption of measurement equivalence across age groups.

The purpose of this study was to investigate measurement equivalence of processing speed measures for different age groups. A structural equation modeling approach was used to investigate a measurement model and the factorial invariance between younger and older adults on speed measures. The analyses concurrently examined whether speed-related abilities dedifferentiate with increasing age. One hundred and forty-four younger and 105 older adults completed 9 measures designed to assess motor speed, alphanumeric speed, and geometric speed. Results indicated that although the number of factors and the factor loadings were invariant across age groups, the interfactor correlations, the variance-covariance matrices, and the unique variances differed across groups. Furthermore, a second-order speed factor seemed to explain much of the variance in the 3 first-order factors, although this higher order factor accounted for slightly more variance among the older group than among the younger group. The results suggest that there is sufficient evidence of measurement equivalence on the current speed measures across the 2 adult age groups and, in addition, provide evidence of dedifferentiation.

Computer assisted three-dimensional reconstruction of brain regions from serial section digitized images. Application to the organization of striato-nigral relationships in the rat.

We have developed a software which allows the three-dimensional reconstruction of brain regions from serial section digitized images. This software, which generates wire-frame three dimensional models, requires at least a 486 PC microcomputer running Microsoft Windows (3.x or 95). Mosaics of high resolution images, covering large brain areas, digitized by means of a camera fitted on a microscope equipped with a motorized stage, are handled by our software as single high resolution images. Serial sets of such images may be segmented and manually aligned. We have utilized this software to study the organization of striatal efferences within the substantia nigra pars reticulata, as well as the distribution of neuronal cell bodies within the substantia nigra pars compacta after micro-ionophoretic application of wheat germ agglutinin conjugated to horseradish peroxidase into the orofacial sensorimotor region of the striatum. The three dimensional representation of anterogradely labeled striatal efferences confirmed and determined the lamellar organization previously postulated from serial plane section micrographs. The distribution in the rat brain of retrogradely labeled nigro-striatal cell bodies, which had not yet been studied after injection of tracer into functionally identified regions of the striatum, revealed two subpopulations: a first one rather dense, located in the anterior half of the substantia nigra pars compacta, which was in close register with the striatal efferences, and a second one, much more scattered and less numerous, located in the posterior part of the structure which extended far from the substantia nigra along the medio-lateral axis. Our three dimensional reconstruction software will now be used to study the neuronal connectivity within the basal ganglia and other brain regions.

Piperine impairs cytochrome P4501A1 activity by direct interaction with the enzyme and not by down regulation of CYP1A1 gene expression in the rat hepatoma 5L cell line.

Modulation of benzo(a)pyrene (BP) metabolism and regulation of CYP1A1 gene expression by piperine in 5L cells in culture was studied. Treatment of cultures with 60 microM piperine for different time periods inhibited metabolism of BP by 50% within 4-8 h. Piperine uptake in 5L cells attained saturation plateau at 8 h and this related with the maximal impairment of BP metabolism. Exposure of cell cultures to piperine for 24 h indicated activation of CYP1A1 gene transcription. There was a 10-fold increase in CYP1A1mRNA and an approximately 7-fold increase in arylhydrocarbon hydroxylase (AHH) activity, while treatment with benzanthacene (BA) increased CYP1A1mRNA by 86- and AHH by 56-fold. Combined treatment with BA plus piperine further increased CYP1A1mRNA contents by about 25%. The BA-inducible AHH activity, however, registered a decrease of about 45%. Piperine neither destroyed CYP1A1-protein nor affected the total cellular protein contents. Exposure of cultures to 0.01 to 3.0 microM trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene for 24 h reduced maximum cellular growth by about 50%. Piperine at 60 microM offered full protection against the diol cytotoxicity. The results, suggest that piperine mediated inhibition of the AHH activity and consequent suppression of the procarcinogen activation is the result of direct interaction of piperine with CYP1A1-protein and not because of down regulation of the CYP1A1 gene expression.

Differential effects of 12-O-tetradecanoylphorbol 13-acetate on cytochrome P-450-dependent monooxygenase activities in rat hepatoma cells: induction of P-450I and suppression of P-450II.

We have studied the effects of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) on cytochrome P-450-dependent monooxygenase activities in several differentiated and dedifferentiated Reuber rat hepatoma cell lines using aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH), ethoxyresorufin O-deethylase (EROD), and aldrin epoxidase (AE) as test systems. The following results were obtained: (1) Exposure of cultures to 400 nM TPA for 18-24 h increased AHH activities in the differentiated lines 2sFou, H41IEC3/G- and Fao as well as in the dedifferentiated line 5L, 1.5-2.5-fold. The phorbol ester did not affect AHH activity in the dedifferentiated line H5. (2) EROD, a marker for P-450I, was induced by the phorbol ester to a similar degree as AHH. (3) A monoclonal antibody directed against P-450I strongly inhibited the AHH activity induced by TPA. (4) The onset of AHH or EROD induction by TPA was much later than that elicited by benz[a]anthracene. (6) In contrast to the induction of AHH and EROD, TPA decreased AE activity, a marker for P-450II, by about 50% in all the cell lines containing this monooxygenase activity. (7) The half-maximum-effect concentration of TPA for inducing or suppressing AHH and AE, respectively, was approximately 20 nM. (8) TPA did not interfere with AHH induction by benz[a]anthracene. However, the phorbol ester moderately decreased AHH induction and markedly suppressed AE induction by dexamethasone. The results indicate that TPA simultaneously induces P-450I and suppresses P-450II forms in rat hepatoma cells. P-450I induction by TPA in these cells did not appear to depend on their status of differentiation. Furthermore, the results suggest that the mechanism of P-450I induction by TPA differs from that elicited by polycyclic aromatic hydrocarbons or glucocorticoids.

The absence of the Ives effect in a deuteranope.

Ives found that when monochromatic stimuli are matched to white by flicker photometry, they are not equal in brightness to the white by direct comparison, and the discrepancy is minimal for yellow but is increased for longer and shorter wavelengths. On the two sides of yellow, the colors are more saturated, and Ives postulated that brightness involves the sum of a chromatic component and an achromatic component and that the chromatic component varies with the saturation. In the case of a deuteranope, one would expect a vigorous chromatic response for yellow and blue stimuli but a poor response for the neutral part of the spectrum. The Ives effect is virtually nonexistent for subject SR, who is a deuteranope. In terms of the zone theory of color vision, this would mean that the blue-yellow chromatic channel contributes little or nothing to brightness. In a normal observer, the blue-yellow mechanism can be isolated by using blues and yellows depurified with white, but in this case the Ives effect is found to exist.