Apolipoprotein E4 enhances brain inflammation by modulation of the NF-κB signaling cascade

Apolipoprotein E4 (apoE4), the major genetic risk factor of Alzheimer's disease (AD), is associated with enhanced brain inflammation. Genome-wide gene expression profiling was employed to study the effects of apoE genotype on hippocampal gene expression in LPS-treated mice, transgenic for either apoE4 or the AD benign allele, apoE3. This revealed that the expression of inflammation-related genes following intracerebroventricular injection of LPS was significantly higher and more prolonged in apoE4 than in apoE3 transgenic mice. Clustering analysis revealed gene clusters which responded differently in apoE4 and apoE3 mice and were significantly enriched in NF-kappaB response elements. Direct measurement of NF-kappaB-regulated genes revealed that their extent of activation was greater in the apoE4 mice. Immunohistochemistry experiments revealed that microglial and NF-kappaB activation were more pronounced in apoE4 than in apoE3 mice. These findings suggest that the increased brain inflammation in apoE4 mice is related to disregulation of NF-kappaB signaling pathway.     

Oxatomide protectsTrichinella spiralis infected mice from lethal anaphylaxis

Infection withTrichinella spiralis in mice was accompanied by allergic sensitization as evidenced by anaphylactic death after intravenous injection of the antigen. Pre-treatment of the animals with oxatomide, a new orally active antiallergic drug, resulted in significant protection of the animals; the lowest effective dose of the compound was 1.25 mg/kg orally. In contrast to cyproheptadine, oxatomide offered little protection against serotonin toxicity in mice.The present data suggest that, in this model of systemic hypersensitivity, the anti-anaphylactic effect of oxatomide can be attributed mainly to inhibition of release of allergic mediators.     

Autosomal recessive inheritance of Nager acrofacial dysostosis.

Nager acrofacial dysostosis is a variant of mandibulofacial dysostosis with severe micrognathia, malar hypoplasia, and radial limb defects. Most cases are sporadic, but autosomal recessive inheritance has been suggested. A family is reported in which two sibs are affected by this syndrome, presenting further evidence for autosomal recessive inheritance. The recognition of this syndrome as a distinct entity has important implications. After the birth of a child with orofacial malformations suggestive of mandibulofacial dysostosis, an exact diagnosis is essential before genetic counselling can be offered.     

The Society for Craniofacial Genetics and Developmental Biology 41st Annual Meeting

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, postdoctoral researchers, medical and dental practitioners, scientists, and academicians who possess an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology.     

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.     

Small Breast Lesion Classification Performance Using the Normalized Axial-Shear Strain Area Feature

Breast cancers that are found and confirmed because they are causing symptoms tend to be larger and are more likely to have already spread to the lymph nodes and beyond. Thus, early detection and confirmation are of paramount importance. The normalized axial–shear strain area (NASSA) feature from the axial-shear strain elastogram (ASSE) has been shown to be a feature that can identify the boundary-bonding conditions that are indicative of the presence of cancer. Recently, we investigated and reported on the potential of the NASSA feature for breast lesion classification into fibroadenomas and cancers. In this article, we investigate the size distribution of the lesions that were part of the previous study and analyze classification performance specifically on small lesions (<10 mm diameter). A total of 33 biopsy-proven malignant tumors and 30 fibroadenomas were part of the study that involved three observers blinded to the Breast Imaging Reporting and Data System (BIRADS) ultrasound scores. The observers outlined the lesions on the sonograms and the lesion size (maximum circle-equivalent diameter in millimeters) was computed from this outline. The ASSE was automatically segmented and color-overlaid on the sonogram, and the NASSA feature from ASSE was computed semi-automatically. Receiver operating characteristic curves were then generated for the subset of cases involving small lesions. Box plots were produced for the two different lesion size groups, small and large, from a logistic regression classifier that was built previously. The results of our study show that approximately 38% and 22% of the fibroadenomas and cancers, respectively, were small. Furthermore, it was found that the NASSA feature resulted in a perfect classification of the small lesions, both in the training data and in the cross-validation. For lesions <10 mm the difference in fibroadenoma and cancer mean scores was 0.73 ± 0.13 (p < 0.001), whereas lesions >10 mm had a difference of 0.52 ± 0.24 (p < 0.001). The results also showed that the small lesions actually had better classification than the larger lesions (>10 mm). These results suggest that the ASSE feature can work equally well, even on small lesions, to improve the standard ultrasound BIRADS–based breast lesion classification of fibroadenoma and malignant tumors.     

Patent foramen ovale

INTRODUCTION: Intentional or unintentional placement of a pacemaker lead into the left ventricle is an uncommon clinical entity that is associated with a high risk for systemic embolization and enormous difficulties in case of explantation. Unintentional implantation through a patent foramen ovale via the mitral valve is the usual pathway for this malposition. METHODS: We report a case where a pacemaker lead was placed intentionally into the left ventricle via a patent foramen ovale for biventricular pacing for resynchronization therapy. Later, the patient developed life-threatening pacemaker lead-associated endocarditis with sepsis. Emergency open heart surgery for lead removal was necessary in the form of a reoperation after bypass graft surgery a number of years earlier. CONCLUSION: Although it is technically feasible to implant the pacemaker lead into the left ventricle via a patent foramen ovale, we consider this option to be obsolete for use with a biventricular pacemaker, due to the multitude of risks, which can, in part, be life-threatening for the patient.     

Left-Atrial Appendage Thrombosis in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation

BackgroundData about the impact of left-atrial appendage thrombosis (LAAT) on early safety and mortality in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) are scarce. We aimed to investigate the prevalence and predictors of LAAT and the outcome associated with this condition in patients treated by TF-TAVI.MethodsRetrospective data analysis was derived from a prospective single-centre registry comparing patients with and without LAAT regarding early safety at 30 days, according to Valve Academic Research Consortium-2 (VARC-2) and 2-year mortality.ResultsLAAT was found in 7.6% of the whole cohort (n = 2527) and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort, n = 1099). Compared with controls, patients with LAAT were sicker, indicated by a higher Society of Thoracic Surgeons (STS) score and burden of comorbidities. Neither VARC-2–defined early safety at 30 days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 29.2% vs 24.2%, P = 0.123; stroke: 5.9% vs 4.7%, P = 0.495) and AF cohort (early safety: 29.1% vs 22.9%, P = 0.072; stroke: 5.6% vs 3.3%, P = 0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared with controls (hazard ratio, 1.41; 95% confidence interval, 1.07-1.86; P = 0.014). However, multivariate analysis of the whole cohort and the AF cohort revealed no association between LAAT and 2-year mortality.ConclusionsLAAT was frequent in patients undergoing TF-TAVI— in particular, in patients with histories of AF—but it was not associated with an increase in periprocedural complications and did not predict 2-year mortality.