Conditional deletion of BMP7 from the limb skeleton does not affect bone formation or fracture repair

While the osteoinductive activity of recombinant bone morphogenetic protein 7 (BMP7) is well established, evaluation of the role of endogenous BMP7 in bone formation and fracture healing has been hampered by perinatal lethality in BMP7 knockout mice. Here we employ conditional deletion of BMP7 from the embryonic limb prior to the onset of skeletogenesis to create limb bones lacking BMP7. We find that the absence of locally produced BMP7 has no effect on postnatal limb growth, articular cartilage formation, maintenance of bone mass, or fracture healing. Our data suggest that other BMPs present in adult bone are sufficient to compensate for the absence of BMP7. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:384–389, 2010     

Children of psychotic mothers. An evaluation of 1-year-olds on a test of object permanence.

Fifteen 1-year-old infants at high risk for later psychopathologic behavior were tested on the Piaget Object Scale. Their performance was compared to that of a matched group of controls at low risk. Results indicate a trend in the high-risk group toward lowered object scale performance. Affective styles were found to vary between the groups. The high-risk infants, particularly those with low scores on the object scale, demonstrated more intense anxiety.     

Measurement of stray light and glare: comparison of Nyktotest, Mesotest, stray light meter, and computer implemented stray light meter

AIM: To evaluate the properties of devices for measuring stray light and glare: the Nyktotest, Mesotest, "conventional" stray light meter and a new, computer implemented version of the stray light meter. METHODS: 112 subjects, divided in three groups: (1) young subjects without any eye disease; (2) elderly subjects without any eye disease, and (3) subjects with (early) cataract in at least one eye. All subjects underwent a battery of glare and stray light tests, measurement of visual acuity, contrast sensitivity, refraction, and LOCS III cataract classification. Subjects answered a questionnaire on perceived disability during driving. RESULTS: Repeatability values were similar for all glare/stray light tests. Validity (correlation with LOCS III and questionnaire scores), discriminative ability (ability to discriminate between the three groups), and added value (to measurement of visual acuity and contrast sensitivity) were all superior for both stray light meters. Results of successive measurements are interrelated for the conventional but not the new stray light meter. This indicates a better resistance to fraud for the latter device. CONCLUSIONS: The new computer implemented stray light meter is the most promising device for future stray light measurements.     

Significance of chest computed tomography findings in the evaluation and treatment of persistent gestational trophoblastic neoplasia

OBJECTIVE: To evaluate whether chest computed tomography (CT) findings in patients with persistent gestational trophoblastic neoplasia (GTN) and a negative chest roentgenogram (CXR) significantly influence clinical outcome and to determine potential clinical predictors of pulmonary micrometastasis STUDY DESIGN: The charts of 201 patients with nonmetastatic GTN (International Federation of Gynecology and Obstetrics [FIGO] stage I) receiving primary treatment with methotrexate (MTX) infusion between December 1985 and December 2000 were reviewed, and data were collected on age, gravidity and parity, FIGO stage, histologic diagnosis, metastatic disease, radiologic findings, surgery, presenting human chorionic gonadotropin (hCG) level, total number of chemotherapy courses and chemotherapeutic agents required to reach remission, and time to remission. The chi2, regression, Kaplan-Meier and log-rank tests were utilized to evaluate the correlation of chest CT with CXR findings, histology of antecedent pregnancy, presenting hCG level, chemotherapeutic requirements and time to remission. RESULTS: Of 30 patients with a negative CXR, 13 (43.3%) had chest CT positive for micrometastasis. Histology of the antecedent pregnancy and mean presenting hCG did not correlate with the chest CT result. There was no significant difference between patients with positive or negative chest CT results in the requirement for > 1 dose of MTX or for additional chemotherapeutic agents. There also was no significant difference in time to remission by chest CT status. Regression analysis using histologic diagnosis, presenting hCG level, age, gravidity and parity as covariates did not reveal any clear risk factors for pulmonary micrometastasis. CONCLUSION: It has been suggested that GTN patients with micrometastases identified on chest CT only are at increased risk of requiring > 1 dose of MTX or of requiring additional chemotherapeutic agents. Our data suggest that chest CT alone is not predictive of clinical outcome. Furthermore, the presence of micrometastases does not correlate with hCG level or histologic diagnosis, and there are no clear risk factors for pulmonary micrometastases.     

Superkids: competent children of psychotic mothers.

In a follow-up study of children of psychotic mothers, the authors examined a subgroup of outstandingly talented, colorful, and competent "high-risk" children. These children and their mothers were given a variety of psychological tests and were interviewed individually. They were then compared with a control group of children whose mothers had no psychiatric illness. The 6 most socially and intellectually competent high-risk children were strikingly more competent, colorful, creative, and talented than the 6 highest functioning control children. They more often reported having a best friend and had extensive and positive contact with an extrafamilial adult. Another important variable in the prediction of high social competence among children at high risk is a warm relationship with the mother.     

Local lymph node assay (LLNA): comparison of different protocols by testing skin-sensitizing epoxy resin system components

Thirteen epoxy resin system components were tested in the LLNA with regard to their sensitizing potency. Lymph node stimulation was quantified not only by measuring the incorporation of [³H]-thymidine into the ear lymph nodes but also the counts of cells recovered from these organs. Equivalent figures were obtained with both endpoints used for the evaluation of lymph node cell proliferation if the reference stimulation indices were adjusted. When dissolved in acetone, all test substances showed skin-sensitizing potential, mainly on the boundary between “strong” and “moderate” according to common potency evaluation schemes. Replacing acetone with acetone/olive oil (4:1) as a vehicle for four selected test items, resulted in considerably lower estimated concentrations for sensitization induction. The challenges in comparing the results obtained by different LLNA variations are discussed.     

Prenatal toxicity of inhaled polymeric methylenediphenyl diisocyanate (MDI) aerosols in pregnant wistar rats.

Mated Wistar rats, 25/group, were exposed to polymeric methylenediphenyl diisocyanate (MDI) aerosol of respirable size for 6 h/day, on gestational days (gd) 6 through 15, at 0, 1, 4, and 12 mg/m3. Maternal clinical signs, body weights, and feed and water consumption were measured throughout gestation. At scheduled sacrifice on gd 20, maternal body, gravid uterine, liver, and paired lung weights were documented. Corpora lutea were counted, implantation sites were identified: resorptions, dead and live fetuses, and placentas were weighed. All live fetuses were counted, sexed, weighed, and examined for external alterations; approximately 50% of the live fetuses/litter were preserved in Bouin's fixative and examined for visceral alterations, and the remaining live fetuses/ litter were cleared and stained with alizarin red S and examined for ossified skeletal alterations. Maternal toxicity was observed at 12 mg/m3, including mortality (2 of 24 pregnant), damage to the respiratory tract, reduced body weights and weight gain, reduced liver and increased lung weights, and reduced gravid uterine weight (the last not statistically significantly different from the control value). Developmental toxicity was also observed at 12 mg/m3, including reduced placental and fetal body weights and an increased incidence of fetal skeletal variations and skeletal retardations. There was no evidence of maternal or developmental toxicity at 1 or 4 mg/m3. The no observed adverse effect concentration for maternal and developmental toxicity was therefore 4 mg/m3. There were no treatment-related teratogenic effects at any concentrations evaluated.     

Chronic pulmonary effects of respirable methylene diphenyl diisocyanate (MDI) aerosol in rats: combination of findings from two bioassays

Two independent bioassays are available which have examined the potential carcinogenicity of monomeric and polymeric methylene diphenyl diisocyanate (MDI) following long-term inhalation exposure in rats. These studies are not directly comparable, however, due to differences in design and conduct of the in-life phase, and differences in nomenclature used for some of the histopathological findings. This paper presents a definitive overview ofthe pulmonary toxicity of MDI developed following a thorough review of both investigations. As part of this process, the test materials and the designs of the studies were compared, and an in-depth review of lung lesions was conducted by an independent reviewing pathologist. This included the re-examination of the original lung slides, supported by an analysis of the exposure regimens, the results of which were used to develop an accurate profile of the doses received by the animals in the two studies. Histopathological findings were then combined with this information to give an overall dose-response curve for both studies as a whole. The range of total inhalation exposures to MDI was calculated as 559, 1972, 2881, 6001, 17,575 and 17,728 mgh/m3. Major pulmonary effects included increased lung weights together with bronchiolo-alveolar adenomas and hyperplasia, and interstitial fibrosis which occurred consistently in both studies, indicating a very similar qualitative response of the lungs to polymeric and monomeric MDI. The quantitative response of the lung was clearly dose-related in each study, and when the studies were considered as a whole a reasonable overall dose-response relationship was apparent for major lung lesions. Lung tumours (in low incidences) only occurred at the highest dose level in both studies (17,575 and 17,728 mgh/m3). For inflammatory and other non-neoplastic pulmonary changes, the lowest dose examined (559 mgh/m3) was regarded as a no-observed-adverse-effect-level for both polymeric and monomeric MDI. It was concluded that the results of the two studies could be combined to serve as a basis for human risk assessment of MDI.     

Dyspnea catastrophizing and neural activations during the anticipation and perception of dyspnea

Dyspnea is an aversive symptom in various diseases. High levels of negative affectivity are typically associated with increased dyspnea and changes in its neural processing. Recently, more dyspnea‐specific forms of negative affectivity such as dyspnea catastrophizing were suggested to contribute to increased perception of dyspnea beyond effects of rather unspecific negative affectivity such as general anxiety levels. The involved neural mechanisms have not yet been explored. Therefore, the present retrospective analysis examined the associations of dyspnea catastrophizing with neural activations during the anticipation and perception of dyspnea. Sixty‐six healthy volunteers underwent 20 blocks of inspiratory resistive load breathing with parallel acquisition of fMRI data. Loads inducing either severe or mild dyspnea (dyspnea conditions) were presented in alternating order, with each condition being visually cued (anticipation conditions). Dyspnea catastrophizing and general trait anxiety were measured with the Breathlessness Catastrophizing Scale (BCS) and the State‐Trait Anxiety Inventory, respectively. Correlating the BCS scores with neural activations during the perception of dyspnea yielded no significant results. However, during the anticipation of dyspnea, BCS scores correlated positively with activations of the anterior cingulate cortex (ACC), even after controlling for general anxiety levels. These activations in the ACC were not related to concurrent respiratory parameters. Results suggest that dyspnea catastrophizing in healthy volunteers is associated with stronger ACC recruitment during dyspnea anticipation. Given the established role of the ACC in processing affective states, affect regulation, and antinociception, this might reflect increased affective and/or top‐down modulatory processing in individuals with higher dyspnea catastrophizing when anticipating dyspnea.