Personality pathology and cognitive-behavioral treatment of fear of flying

Studies have been inconclusive about the influence of personality pathology on treatment outcome in anxiety disorders. In general, it has been presumed that treatment outcome is negatively influenced by the presence of personality pathology. This is a study of the prevalence of personality pathology among persons who were seeking help for fear of flying. Moreover, the effects of personality pathology on the results of a multimodal, standardized, cognitive-behavioral fear of flying treatment program employed by an agency that specializes in treating people with fear of flying were studied. Personality pathology was determined with a self-report questionnaire, which provides ICD-10 diagnoses of personality disorders and dimensional severity scores for personality pathology. Treatment outcome was assessed with three different fear of flying questionnaires. Based on clinical judgment after individual-case conceptualization, participants (N=922) were assigned to a particular treatment for fear of flying. Self-report data for fear of flying were collected at pretreatment and at 3, 6 and 12-month follow-ups in 659 participants who followed the 2-day treatment program. Moreover, the number of flights made in the year following treatment was determined.The results of this study showed that participants with personality pathology, mainly from cluster C (anxiety), report greater fear of flying before treatment than participants without personality pathology. After treatment fear of flying was significantly reduced. Presence of personality pathology was not predictive of the number of flights after treatment and scores on the VAFAS scale at short or long term. Only on two questionnaires for fear of flying collected at short-term participants with personality pathology obtained significantly higher scores, although the size of the differences was relatively small. It was concluded that participants with personality pathology also benefited from fear of flying treatment and that the presence of personality pathology although cannot be regarded as a contra indication for a standardized, cognitive-behavioral group treatment.     

Urticaria pigmentosa localized on radiation field

A woman previously treated by radiotherapy for a breast cancer developed urticaria pigmentosa mainly restricted to the irradiation field, without any systemic symptoms. Localized forms of urticaria pigmentosa are exceptional, and their triggering factors are poorly understood. Several hypotheses can be discussed in this peculiar observation, among which a direct role of radiotherapy in the occurrence of cutaneous lesions cannot be ruled out.     

How does the Hospital and Anxiety and Depression Scale measure anxiety and depression in healthy subjects?

Many anxiety and depression scales are commonly used, although the assumption that they all measure the same construct may be questioned. Thus, researchers have to pay attention to the nature of the scales they use. The Hospital Anxiety and Depression Scale (HADS) was constructed in 1983 to allow a rapid and separate measure of depression and generalised anxiety. Surprisingly, since its introduction, there has been no comprehensive documentation of its psychometric properties. Therefore, as a contribution to assessing the construct validity of the HADS, we conducted a set of confirmatory factor analyses in a sample of 195 healthy students. None of the formerly proposed models fit our data. We were able to split the original Anxiety subscale into two components that we have labelled 'Anxiety' and 'Restlessness', while the original Depression subscale is slightly modified. The results are discussed from both clinical and theoretical points of view.     

Instrumental activation of bid by caspase-1 in a transgenic mouse model of ALS

Transgenic expression of mutant superoxide dismutase-1 (SOD1) produces an animal model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We have previously shown that the mitochondrial-dependent programmed cell death (PCD) pathway, including the redistribution of Bax, the cytosolic release of cytochrome c, and the activation of caspase-9, is recruited during neurodegeneration in spinal cords of transgenic mutant SOD1 mice. Herein, we show that the pro-PCD protein Bid is highly expressed in spinal cords of both wild-type and transgenic mutant SOD1 mice. While full-length Bid is found in the spinal cord of the two groups of mice, its cleaved form is only seen in transgenic mutant SOD1 mice, as early as the beginning of symptoms. In contrast, activated caspase-8, which is known to cleave Bid, is detected only at the end-stage of the disease. We also found that the expression of a dominant negative mutant of caspase-1 attenuates Bid cleavage as well as the mitochondrial release of cytochrome c, and the ensuing activation of caspase-9 and -3 in spinal cords of transgenic mutant SOD1 mice. These findings suggest that Bid cleavage may occur in this model by a pathway other than caspase-8 and shed light onto the molecular correlates of the previously reported beneficial effect of caspase-1 inhibition in transgenic mutant SOD1 mice.     

Synthesis and DNA interaction of a mixed proflavine-phenanthroline Tröger base

We report the synthesis of an asymmetric Tr?ger base containing the two well characterised DNA binding chromophores, proflavine and phenanthroline. The mode of interaction of the hybrid molecule was investigated by circular and linear dichroism experiments and a biochemical assay using DNA topoisomerase I. The data are compatible with a model in which the proflavine moiety intercalates between DNA base pairs and the phenanthroline ring occupies the DNA groove. DNase I cleavage experiments were carried out to investigate the sequence preference of the hybrid ligand and a well resolved footprint was detected at a site encompassing two adjacent 5'-GTC.5-GAC triplets. The sequence preference of the asymmetric molecule is compared to that of the symmetric analogues.     

Oxygène, stress oxydant et supplémentations antioxydantes ou un aspect différent de la nutrition dans les maladies respiratoires

Dioxygen is an element essential to our survival, our life, our development, our capacity of adaptation. Nevertheless, dioxygen is also at the origin of toxicity, acidity, deterioration, degeneration. Indeed, when the metabolism of dioxygen is altered, as in the respiratory diseases, an “oxidative stress” can appeared and induced metabolic anomalies associated with important consequences. Oxidative stress is defined as an imbalance between pro-oxidant (reactive oxygen species) and antioxidant factors, in favour of the former. The genomic, metabolic and functional modifications induced by oxidative stress were implied in the development of various degenerative diseases. Antioxidant treatments, in a nutritional or pharmacological way, appeared consequently as new potent therapies. In this review, the role of dioxygen in the cellular metabolism, and in the production of the reactive oxygen species is discussed. The negative effects of the oxidative stress on the organism are reported. Finally, the results of the studies on the nutritional antioxidant treatment firstly in the degenerative diseases, secondly in a chronic respiratory disease, the chronic obstructive pulmonary disease, are discussed in a last part.     

Pure-tone threshold description of an elderly French screened population.

OBJECTIVES: To describe the distribution of pure-tone hearing thresholds of a Caucasian population living in the south of France aged 70 years and older. To establish age- and sex-adjusted normative hearing thresholds based on results of subjects free of noise and ototoxic drug exposure and to compare them with hearing thresholds of exposed (E) subjects. DESIGN: Cross-sectional analysis of a longitudinal epidemiologic cohort study. SETTING: Montpellier suburb, south of France. PARTICIPANTS: A total of 778 subjects 70 years old and older were examined. Noise exposure, ototoxic medication use, and medical history were collected. Hearing thresholds were obtained via pure-tone audiometry. After excluding patients with ear-related disease, 659 subjects were further analyzed (270 men and 389 women). Noise or ototoxic medication exposure was found in 364 subjects (E subjects), whereas 295 had no exposure (nonexposed [NE] subjects). METHODS: Median pure-tone thresholds, lower deviation, and upper deviation were calculated for the NE subjects with a statistical method similar to the ISO 7029 norm and were compared with thresholds of E subjects. RESULTS: Hearing thresholds, especially in high frequencies, increased with age more for women than for men. Median thresholds of E subjects were significantly higher than those for the NE sample in men. CONCLUSION: Age- and sex-adjusted hearing thresholds could well be useful in the study of the impact of environmental and genetic factors on hearing loss in the elderly. The next step would be to quantify the impact of noise, ototoxic drug exposure, and genetics using these age- and sex-adjusted thresholds.     

Increasing digesta viscosity using carboxymethylcellulose in weaned piglets stimulates ileal goblet cell numbers and maturation

Intestinal mucin, a family of glycoproteins secreted by goblet cells, is the main constituent of the mucus protecting the gastrointestinal tract. For optimal mucosal protection, both the quantitative and qualitative characteristics of mucin are essential. To evaluate how viscosity influences ileal apparent digestibility and mucin biology, a highly viscous nonfermentable soluble polysaccharide, carboxymethylcellulose (CMC), was fed to weaned piglets for 15 d. The ileal crude mucin concentration was determined by ethanol precipitation, and changes in goblet cell subtypes were analyzed by the histochemistry of ileal and colonic tissues. As expected, CMC increased the viscosity of ileal digesta and the moisture of feces (P < 0.001). The crude mucin concentration and output at the ileum were higher (P < 0.05) in pigs fed CMC than those fed the control diet. Increasing intestinal content viscosity in pigs fed CMC had no significant effects on the ileal apparent digestibility of dry matter, organic matter, nitrogen, and minerals. The number of total ileal goblet cells per villus also was higher (+30%, P < 0.05) in pigs fed the CMC diet compared with controls. This increase was essentially accounted for by increased numbers of acidic and acidic sulfated mucin-containing cells (+30%, P < 0.05). Trends (P = 0.06) toward decreased numbers of neutral and acidic mucin-containing cells in ileal crypts were also noted. In conclusion, increasing intestinal content viscosity in weaned piglets fed CMC increased the ileal mucin output and numbers and maturation of goblet cells in ileal villi without effects on the apparent digestibility of the diet.     

Short-term survival of newborn neurons in the adult olfactory bulb after exposure to a complex odor environment

In the olfactory bulb of adult mice, new neurons are continually integrated into existing neuronal networks. Previous studies have demonstrated that exposure to a complex odor environment increases the incorporation of newborn bulbar neurons without modifying the proliferation rate. Whether this incorporation is transient or leads to the long-lasting presence of new neurons has not yet been answered. Because a transient increase of new neurons impacts olfactory information processing differently than a long-lasting increase, we conducted experiments to investigate the time course of survival and cell death of newly generated bulbar neurons following exposure to an enriched olfactory environment. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were counted at several survival time points thereafter. Interestingly, whereas the number of surviving BrdU-labeled cells was elevated at the time when animals were withdrawn from their enriched housing, this number returned to control level 1 month later. Similarly, when olfactory memory was investigated, we found that the improvement of short-term memory, induced by enriched odor exposure, lasted less than 1 month. These findings indicate not only that the recruitment of newborn neurons closely followed the degree of environment complexity, but also that olfactory memory is tightly associated with the level of ongoing neurogenesis in the adult olfactory bulb.     

Fibrillar type I collagens enhance platelet-dependent thrombin generation via glycoprotein VI with direct support of alpha2beta1 but not alphaIIbbeta3 integrin

The role of collagens and collagen receptors was investigated in stimulating platelet-dependent thrombin generation. Fibrillar type-I collagens, including collagen from human heart, were most potent in enhancing thrombin generation, in a way dependent on exposure of phosphatidylserine (PS) at the platelet surface. Soluble, non-fibrillar type-I collagen required pre-activation of integrin alpha2beta1 with Mn2+ for enhancement of thrombin generation. With all preparations, blocking of glycoprotein VI (GPVI) with 9O12 antibody abrogated the collagen-enhanced thrombin generation, regardless of the alpha2beta 1 activation state. Blockade of alpha2beta1 alone or antagonism of autocrine thromboxane A2 and ADP were less effective. Blockade of alphaIIbbeta3 with abciximab suppressed thrombin generation in platelet-rich plasma, but this did not abolish the enhancing effect of collagens. The high activity of type-I fibrillar collagens in stimulating GPVI-dependent procoagulant activity was confirmed in whole-blood flow studies, showing that these collagens induced relatively high expression of PS. Together, these results indicate that: i) fibrillar type-I collagen greatly enhances thrombin generation, ii) GPVI-induced platelet activation is principally responsible for the procoagulant activity of fibrillar and non-fibrillar collagens, iii) alpha2beta1 and signaling via autocrine mediators facilitate and amplify this GPVI activity, and iv) alphaIIbbeta3 is not directly involved in the collagen effect.